Dating with Chronic Illness – A Thorny Topic

Dating with chronic illness is no easy, straightforward feat for either party. Questions like this are all over Quora and Reddit: “Would you date or marry a person with chronic illness?”. So I thought I’d share my perspective, as a person who’s chronically ill and disabled. Over the years, I’ve been in long-term, short-term and even long-distance relationships. I’ve also tried various dating apps, and met partners through friends. I much prefer the latter, but it does get harder the older you get!

P.s. The original version of this post was published on 26 February, 2017 (8 years ago!). More insights into dating, relationships, self-worth, disability and chronic illness have been added 🙂

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

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Just Like Chronic Illness, Every Relationship is Unique

I’ve been fortunate enough to have had relationships with partners from extreme ends of the spectrum. It gives me insight into different perspectives, which enables me to identify and appreciate certain characteristics better. Their opinions about our future together were diverse, and so were their attitudes towards my daily health struggles. Before going further, I’d like to state that the purpose of this article isn’t to bash anyone at all. Everyone is entitled to how they want to live their lives, and who they want to do that with, for better or for worse.

Partners Who Saw My Chronic Illnesses as a Liability

My first relationship was with a guy whose greatest desire was to start a family of his own, and it troubled him that I never seemed to get better. He did not like the open-ended, variable timetable of my chronic illnesses. Neither did he want to start with a ‘deficit’ before even trying for a child.

I underwent a few surgeries whilst we were dating, and he felt tormented that he could do ‘nothing’ to make it better. Yet, he never provided any emotional support, and would often bail out on the bad days. I ended up having to be stronger for him, because ‘it was difficult for him too’. I would always give in to him, because I thought that I had less rights to my own opinions. It was already a burden for someone to be with me, what more could I ask for?

Dates Who Tried, Then Ran

I’ve also dated men who were willing to try things out for a couple dates, but who were constantly analysing my limits. This isn’t too fair in my opinion for several reasons. First, I have good and bad days, and you might be seeing me during a bad week. Second, and this is applicable to healthy individuals, too – it takes a bit of time to truly know who a person is, both the good and bad. Third, their assessment of my capabilities is usually inaccurate, because it tends to be biased. Unfortunately, when you’re chronically ill or disabled, people tend to hyperfocus on the limitations and judge you more keenly and immediately.

Then there are those dates where they see me arrive with a walking stick on a bad day. We have a short, polite chat, before they run for the hills and hide themselves behind a wall of silence. Whilst this feels unpleasant, I have learned to accept that it’s all part of the dating game, sick or otherwise.

Divorced Partners are Not Necessarily More “Chill”

There was a period of time I said to myself, “well, let’s wait for all the married men to get divorced. They should be wiser and more open-minded now, and realise that there’s more to a relationship than chronic illness”.

This turned out to be false. I obviously can’t speak for all divorced men, but the ones I have personally interacted with were fairly extreme. They were either paranoid (“you haven’t replied to my message in 24 hours, even though there are two blue ticks!”), or fixated on a certain ideal (hyperfocused on a singular quality, to the exclusion of all other qualities). Chronic illnesses still bothered most of them. Divorced men are not necessarily wiser than an unmarried person. They are still human, with strengths and flaws alike.

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Partners Who Were Accepting of My Chronic Illnesses

My next partner always saw the future in a hopeful light, and went with the flow of life. For example, he believes that healthcare and medicine can only improve as more scientific advances are being made. He saw me at my worst, yet never once treated me as a lesser human being.

I know for sure that life will never be easy with me, yet it was a non-issue to him. He claims that there is nothing wrong with me at all, and that I didn’t affect his lifestyle. Another revelatory phrase he made was that every relationship has its own set of problems anyway, whether the partners were sick or healthy. (You can read more brilliant utterances about relationships he made in this post.)

I found that I grew with him as a person, because of his support to the very end. He never undermined any desire I had for education, which comes in many forms. Apart from the intellect, it also consists of life skills, hobbies, and most importantly, self-awareness.

Mental and invisible health issues are often seen as suspicious in the eyes of the public, but I never felt stigmatised by him. I could display my psychological and physical pains at the level of torture that they were truly at. That brought so much relief – just to have someone who believes you, and who never belittles the impact your experiences have on you.

Whilst we have broken up, we are still friends, and I visit him and his family every Christmas. I am genuinely happy for him, because I believe people like him truly deserve the best that life has to offer.

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The Most Important Thing I’ve Learned from Dating with Chronic Illness

If there’s one I’ve learned over the years from dating as a person with chronic illness, it is to have some respect for myself. If I were dating someone who treated me with contempt, resentment or blame, then I – a person with chronic illness and disability – would leave them.

With age, experience and the freedom I have had to grow, I’ve learned that I am worth just as much as any other person out there. So what if my illnesses are permanent? There is only one me amongst the billions of us on this planet, and we are all worth something in that regard.

In fact, an aura of quiet self-confidence and knowing your inherent self-worth can be attractive traits to potential partners. You are as deserving of love as any other human being; we are all part of the same world, and return to dust just the same.

“I’ve learned that I am worth just as much as any other person out there..There is only one me amongst the billions of us on this planet, and we are all worth something in that regard.” #SelfWorth #ChronicIllness #disability #relationships
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All Human Beings Need a Little Help to Get by in Life

There is no doubt that a person with chronic illness will need more help than someone who is healthy just to get by. Many situations might test your patience, question your love and flirt with your morality. In modern day culture, independence is a revered trait, and we like to think that we are independent beings.

But that is not how humanity has thrived over the centuries. We are social creatures built for community. It is an important aspect of social well-being. Yes, even introverts need a touch of human connection every now and then, in order to thrive.

And no human being is truly independent, anyway; just cut off their oxygen supply for a minute. We all depend on something to survive and thrive – a relationship with a chronically ill or disabled person also has the potential to help you develop as a person, and to live a fulfilling life ultimately. Perhaps even more so, because it will force you to reflect on your priorities, purpose and goals in life more than you would otherwise.

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How Chronic Illness & Disability has Influenced the Way I Approach Romantic Relationships

To be honest, after having faced several life-and-death situations, I’ve become more stoical than I already was to begin with. Acceptance took me years to grasp, and I often need to learn to accept a new diagnosis all over again. However, I will vouch that it is the best coping tool and strategy that has enabled me to live my life, despite chronic illness. And if we’re being completely honest here, I am still grieving the loss of function in my knees. Grief and acceptance are two sides of the same coin; they come and go like visitors, and are not linear processes.

I actually adopt this mindset of acceptance when I approach relationships and dating with chronic illness as well. “Whatever will be, will be”, “que Será, Será”. For example, I never worry if my partner is going to cheat on me. If they do, then I will just up and leave – obviously it wasn’t meant to be.

Interestingly, this bothered a boyfriend, as he assumed that it meant that I didn’t like him enough to care. However, I’ve dealt with way more harrowing experiences, so I consider many everyday problems as trivial. You could say that it’s a bit like scar tissue – tougher, but less sensitive, which can be both a good and bad thing.

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Other Insights I’ve Gained from Dating with Chronic Illness & Disability

Whilst it is true that anyone can become disabled at any time, this fact doesn’t sink into healthy people’s brains regardless. I can’t blame them for that, as the devastation of chronic illness and disability is impossible to grasp, unless you live that reality yourself. Humans are also wired for self-preservation. This means that they instinctively avoid things that may contribute towards the eradication of their lives or legacies.

If I’m going to be logical, health is wealth. Who doesn’t want to be healthy? So yes, we are starting out with a deficit in life. However there is an extremely fine line between worth1 and worth2 that people often confuse. What do I mean by that? This statement from Positive Psychology helps to clarify it a little:

“Self-esteem is what we think and feel and believe about ourselves. Self-worth is recognizing ‘I am greater than all of those things.’ It is a deep knowing that I am of value, that I am loveable, necessary to this life, and of incomprehensible worth.”

In brief, people often confuse self-worth – where every human being is inherently valuable, and deserving of love and respect – with material or tangible value. It’s an issue of feeling secure or insecure. In a ‘modern’, capitalist era, it’s not that much of a shocker either, as we’ve been exposed to such ideals from our childhoods, and our parents may have even placed an emphasis on it.

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My Best Tips for Dating with Chronic Illness

The communication style, character, values, sense of humour and lifestyle of all the people I’ve dated were vastly different. So it’s been an interesting, though admittedly exhausting, ride thus far.

I also broke both my knees fairly recently, no thanks to Lupus and long-term steroid treatment, plus developed yet more chronic diseases. These unasked for additions have definitely made dating much harder, as my disabilities become more and more apparent. Sure, rejection from being chronically ill and disabled stings, but it’s also for the best. I would be walking on eggshells, if I were with a partner whom I had to constantly prove and pretend I was healthy to.

Dating Tips for the Chronically Ill & Disabled

Here are a few of my personal golden rules, when it comes to dating with chronic illness and disability. Your list might look different, based on your own comorbidities, life experiences and personality.

1. Have some self-respect. If a potential partner disrespects you in any way, leave. It’s better to be single than with someone who doesn’t treat you right. This will only compound problems in your life, such as mental health issues.

2. Be open-minded and explore. Yes it’s true – the more nets you cast, the more fish you get. This strategy definitely doesn’t work for everyone, due to a myriad of reasons, such as limited energy, religious beliefs, etc. But I believe in trying things out.

   I mean, it’s just one date over coffee or dinner. At worst, you waste some time and discover that you’re incompatible. The reasons may not even be related to chronic illness – it happens to regular people, too. At best, you find your special person. Whilst I’m not an extrovert, I take it as an opportunity to socialise. I also believe that I can learn something from every person I meet – even from the bad dates. In that sense, there is no loss.

3. Do they offer to pay for the first date? I am definitely not looking for a free meal and will refuse the offer, but this simple act of generosity tells me a few things. Basically, if they can’t even be generous financially, which is arguably the easiest, then how generous can they be with other more important or ‘difficult’ aspects of life, such as quality time, medical emergencies, or if you had kids?
4. Just be yourself. In the wise words of Dave Grohl, “No one is you and that is your biggest power”. You might be surprised who falls in love with you – the real you. In the mess and glory of your full humanity. Even Joker has his Harley Quinn, so that gives me hope.

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   “In the wise words of Dave Grohl, “No one is you and that is your biggest power”. You might be surprised who falls in love with you - the real you. In the mess and glory of your full #humanity.” #spoonie #ChronicIllness #disability #dating
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5. Know that you will face rejection, and be okay with that. Whilst we might face more romantic rejections than an abled individual, there is an upside to that as well – we only get to be with the best sorts of people on this planet. In that sense, chronic illness is an automatic filter that sifts out the bad eggs.
6. Know your self-worth. It is also important to be aware of your self-worth at all times – whether you’re single or in a relationship. Ironically, it was chronic illness that forced me to hone this awareness through acceptance. Self-acceptance isn’t an admission of failure; rather, it asks us to put our ego aside in order to unlock possibilities, be at peace, and regain a sense of freedom.

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Dating Tips & Insights for Potential Partners

So, someone interesting has caught your eye. You think that they may be your ‘type’ of person. The ‘problem’? They have a long-term illness or disability. This section addresses some questions you may have, but are unsure who to ask, or if it’s appropriate to ask. I will try to be as unbiased as I possibly can.

1. Understand that there is no perfect partner or relationship. Every single person brings a new dynamic to a relationship. There are pros and cons to each dynamic. Decide what matters most to you most.

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   “There is no #perfect partner or #relationship. Every single person brings a new dynamic to a relationship. There are pros and cons to each dynamic. Decide what matters most to you most.” #DatingTips #ChronicIllness #RelationshipGoals
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2. Don’t ghost. What’s up with ghosting these days? This is my number one pet peeve when it comes to dating in general. If you decide that it’s not going to work out, do the courtesy of letting the other party know, so they get some closure. Why lead someone on before disappearing into the ether?

3. Shift your perspective. Something interesting my ex-turned-boyfriend-again said to me: “Your chronic illnesses have some advantages, too. It enables me to have my own space, alone time, and time for other friends”.

   I’m always happy to oblige because it means I get some me-time as well, without feeling pressured to do ‘coupley things’. Don’t get me wrong. Coupley things are important, as they generate memories and build bonds. But as a person with chronic pain and fatigue, my energy bar is limited, and I need more downtime than others.

   Another caveat – said boyfriend is older now, so he’s seeking different experiences in life as well. Age does play a part to an extent. In a sense, his body has ‘caught up’ a little with mine. Whilst he’s definitely still a social creature, he also appreciates time at home a little more now. So we watch films and play chess at home, and go out for the occasional brunch, party or exhibit.

Conclusion to Dating with Chronic Illness

This article is a sum of my experiences in regards to dating with chronic illness and disability thus far, but the story hasn’t ended yet. (Does it ever end, really?) I am still learning as I go along, and will add to this post should I gain any other insights.

I would also love to hear about your experiences in regards to dating with chronic illness or disability. What were your best and worst experiences, and why? If you’re happily married, how do you make it work? I would love to learn more from you as well!

And finally, if you’re an able-bodied individual, I’d love to hear your thoughts, questions and concerns as well. You can post an anonymous comment if that makes you feel more comfortable. I promise to be as open-minded and non-judgemental as I can. I believe in open, proactive discussion, as opposed to allowing misconceptions or fears to fester in the dark closet of your mind.

Happy dating to one and all – I hope you find your special person ♥️

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Two New Diagnoses – Epiphrenic Esophageal Diverticulum & Mitral Valve Stenosis

Whilst I haven’t heard much good news in a long time, I did not expect 2025 to be a harbinger of such terrible news. It seems like I will need to get two major surgeries done, one for a severe mitral valve stenosis, and the other for an epiphrenic esophageal diverticulum. Well technically, epiphrenic esophageal diverticula, since there are two of them. Oh, and I also broke my molar tooth on Christmas Eve, so that was a bonus.

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

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Classifications for Esophageal Diverticulum

To be honest, the diagnosis for epiphrenic esophageal diverticulum scares me more than the mitral valve stenosis, only because it’s so rare. In practice, esophageal diverticulum is divided into a few different types of classifications from an anatomical and etiopathogenic point of view (Constantin et al., 2023). They are also subdivided based on their location. WebMD summarises the different types of esophageal diverticula here, although the classifications can get even more fine-grained than that (Whitten, 2024, February 20).

However, from what I’ve gathered after reading multiple medical journals, there is currently no agreed upon standard for treatment. Classifications for the disease itself are not even ‘finalised’, so to speak. Meaning there is no handbook or protocol for doctors or surgeons to refer to for this condition, and it’s mainly ‘play by ear’. Both my surgeon and doctor at the hospital have only seen one case in their career.

I’ll talk about the stenosis in a separate post, as I would like to focus on my diagnosis and symptoms for epiphrenic esophageal diverticulum in this one. This post is part of a two-part series. I will share my personal experiences in this one; you can find more research and facts on esophageal diverticulum in this post.

How I Learned About My Epiphrenic Esophageal Diverticulum

I reluctantly admitted myself to the A&E/ER one evening, as my forearm was bloated and swollen. It felt like my skin was going to burst. The only reason I had gone to the A&E was because the GP had assumed it was an abscess.

The rheumatology team saw me the next day, whilst I was snoozing along the corridor of a random ward. They were collectively certain that it was a blood clot, considering I have Antiphospholipid Syndrome, a blood clotting disorder. A few scans and tests later, they were all surprised that it wasn’t a blood clot, neither was it a fracture.

They did however, find some liquid near my lung, and the outpouching characteristic of esophageal diverticulum. According to Constantin et al. (2023), “somewhere between 0.06 – 4% [of epiphrenic esophageal diverticulum] are discovered incidentally, radiologically”.

The swollen arm and liquid in the lung subsequently resolved on their own. In fact, when they wheeled me in to do a pleural biopsy, they wheeled me back out as the surgeon said that ‘there was nothing to biopsy’. This is why I rarely rush to the A&E for every pain, even if extreme. Living with chronic illness means constant pain, and the occasional weird symptom.

My own rheumatologist said that the esophageal diverticula probably have been there for some time. He also said it was probably unrelated to my other autoimmune diseases, though I really beg to differ. I personally think it doesn’t make sense that none of my long list of medical conditions are related.

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My Epiphrenic Esophageal Diverticulum Symptoms

According to Sato et al. (2023), the main symptoms of esophageal diverticulum are “dysphagia, regurgitation, weight loss, heartburn, respiratory complaints, and retrosternal pain when swallowing food”.

My own biggest problem was and is regurgitation, especially whilst asleep in the middle of the night. I wake to violent fits of coughing, as my esophagus tries to purge the food trapped within the pouches. Sometimes my throat is so irritated that I vomit. In fact, it happened twice again last night.

At first, I had simply assumed that it was GERD/acid reflux, as I am on long-term steroid therapy for Lupus and Sjögren’s disease. Plus I drink way too much coffee, and my eating habits are not the best (yes, sue me). When I received the diagnosis for epiphrenic esophageal diverticulum, everything made so much more sense.

Other symptoms I’ve had to date are: minor incidents of dysphagia (trouble swallowing food), and being really gassy. My digestive system makes a lot of weird noises, and I feel bloated and uncomfortable. These are sporadic with no fixed pattern. My doctor has said before that I probably have Irritable Bowel Syndrome (IBS) too, so I’m not sure what’s triggering what. Chronic illness comorbidities are fun like that.

In addition, my throat often feels scratchy, as if there are tiny specks of food trapped within it, plastered to the ‘walls’. There are ‘better’ and worse days as well. On the ‘better’ days, the symptoms are mostly quiescent with some minor coughing. On bad days, that ‘stuck’ feeling is there for almost 24 hours, and I am unable to eat without vomiting.

My Increase in Symptoms

The symptoms rapidly became worse over time. I am now being involuntarily woken almost every night by violent coughing, regurgitation and vomiting. On a ‘better’ night, I wake once or twice. On a ‘bad’ night, that would be at least every 2 hours.

Combine that with horrendous chronic urticaria that antihistamines barely alleviate, it means that I hardly get a good night’s sleep. In fact, that happened again last night, as I was up until 6am scratching and coughing.

Unsurprisingly, this isn’t great for my physical or mental health, as I feel extremely frayed at the edges, and completely worn out. What sort of life is this, if I am in pain and discomfort both day and night? What makes it even more depressing is that there is no medication to even relieve some of the symptoms either.

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More Information About Epiphrenic Esophageal Diverticulum

This section covers more about epiphrenic esophageal diverticulum specifically. You can read the research post for more information about esophageal diverticulum in general.

My two diverticula are mainly epiphrenic in nature (towards the tail end of the esophagus), although one is slightly higher up. Out of the various types of esophageal diverticulum, epiphrenic esophageal diverticulum comprises less than 10% of all cases, with an estimated incidence of 1:500,000 per year (i.e. 1 out of half a million people) (Abdollahimohammad et al., 2014). The most common is Zenker’s diverticulum, which occurs at the top end of the esophagus.

According to Alicuben et al. (2023), patients with epiphrenic esophageal diverticula are symptomatic only about 10% to 20% of the time. Symptoms tend to begin when the diverticulum becomes bigger than 5cm (Abdollahimohammad et al., 2014).

Having said that, both my epiphrenic esophageal diverticula are a little smaller than 5cm, and I have been progressively symptomatic. I’m unsure if that’s good or bad luck. Good because I guess, well, treating something earlier is usually better than later. Bad because the symptoms are obviously not fun.

The Complications of Epiphrenic Esophageal Diverticulum

Many symptoms of epiphrenic esophageal diverticulum are similar to other gastrointestinal and common medical conditions, such as acid reflux or side effects of NSAIDs. As a result, many patients with epiphrenic esophageal diverticulum are diagnosed late, which can lead to further complications, such as “gastrointestinal bleeding, aspiration pneumonia or cancer” (Conklin et al., 2009).

The incidence of cancer in patients with epiphrenic esophageal diverticulum is around 0.3% to 3%, and it is often at an advanced stage when discovered (Conklin et al., 2009; also see: Hjern et al., 2015). According to Constantin et al. (2023), there is also the risk of developing esophageal cancer, around 10 years after symptomatic esophageal diverticulum.

Some Other Characteristics of Epiphrenic Esophageal Diverticulum

According to Constantin et al. (2023) there is “no correlation between size and retentive character” for epiphrenic esophageal diverticulum in particular. That means that food and liquid can get stuck regardless of the size of the epiphrenic esophageal diverticulum, to give rise to symptoms.

In addition, “one of the early signs of food stasis in a pharyngeal-ED [esophageal diverticulum] is the appearance of hydro aerial noises when ingesting fluids”. As a result of food stasis, sialorrhea (hypersalivation) occurs (Constantin et al., 2023).

After reading that, I wondered if my drooling at night is a consequence of the epiphrenic esophageal diverticula. But as I need to wear a mouthguard for bruxism and TMJ disorder issues as well, I suppose it could be multifactorial.

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Confirmation of My Epiphrenic Esophageal Diverticulum Diagnosis – a Barium Swallow Test

After the incidental finding of the epiphrenic esophageal diverticulum, I was scheduled for a barium swallow test. This is one of the more definitive tests for esophageal diverticulum, and also certain motility disorders such as achalasia (Sudarshan et al., 2021).

I was made to drink a chalky liquid at intervals, as the medical team watched and timed the flow under fluoroscopy (a type of x-ray that shows the movement of organs in real-time) (MedlinePlus, 2024, August 27). The mixture tasted quite nice to me, a bit like yoghurt, but don’t take my word for it as the technician said that no one else likes it. The doctors’ biggest concern was achalasia, which the team decided that I did not have based on the test. They were also able to measure the size of the diverticula and gather other information from the barium swallow test.

Other Essential Preoperative Tests for Epiphrenic Esophageal Diverticulum

I will need to get surgery done in my surgeon’s opinion. Whilst it’s a fairly high-risk surgery, I am going to agree with him, as the symptoms are becoming unbearable and interferes with my life every day. Some preoperative tests will need to be done, namely an upper endoscopy and manometry.

Whilst the surgeon has said that the manometry might not be necessary since we’ll need to do a fundoplication (an anti-reflux procedure) during the Heller’s myotomy (surgery) regardless, I insist upon it. This is because epiphrenic esophageal diverticulum mostly stems from a motility disorder, so it is best to treat the underlying cause if so. Whilst the fundoplication might treat any existing motility disorder, I think it’s best to actually know what the disorder is, if there is indeed one.

According to Alicuben et al. (2023), “failure to identify and treat the underlying motility disorder during diverticulum resection has been associated with high rates of recurrence and leak along the staple line in the range of 10% to 20%.” They also state that, “specifically, failure to perform an adequate myotomy in such patients has yielded leak rates exceeding 25% when diverticulectomy alone is performed”.

You can learn more about these diagnostic tests, surgeries and why they’re important in the post here.

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General Symptom Management for Epiphrenic Esophageal Diverticulum

As mentioned, there is no medication to help with symptom relief, and the doctors don’t have much clue about it either. The advice I was given by the gastroenterologist was rather generic, and there aren’t many tips online either. The closest I have found for managing epiphrenic esophageal diverticulum are general esophageal soft food diet tips.

A list of esophageal soft food diet tips can be found on the Cedars Sinai (2018, May 30) website, and includes: eating slowly in small amounts, chewing thoroughly, drinking fluids whilst eating to flush the food down, sitting upright whilst eating and up to 60 minutes after, avoiding food 3 hours before sleeping, avoiding caffeinated beverages, avoiding tough meats, abrasive foods and breads with chewy textures, and to stop eating when you start to feel satiated. This is pretty much what the gastroenterologist has advised me to do for symptom management of my epiphrenic esophageal diverticula.

You may or may not have trouble digesting food in and of itself with epiphrenic esophageal diverticulum. However, many of the symptoms mimic those of esophageal cancer or a motility disorder. Thus, many of the symptom management tips closely resemble these diseases. It also largely depends on your personal symptoms, how and when it affects you. For instance, regurgitation whilst sleeping is my biggest symptom, so my management plan might look different from yours, if you mostly get dysphagia instead.

Dietary changes and eating times are primary ones, however. According to Yam et al. (2023, April 24), “if patients are not surgical candidates, then management with diet changes such as eating bland food and drinking water after every bite to help flush any food out of the diverticulum is recommended”.

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How I’m Personally Managing My Epiphrenic Esophageal Diverticulum Symptoms

It’s been a lot of trial and error for me, personally. I have a rough idea of which types of food cause the most damage, having learned the painful way. By sharing these personal experiences, I hope that it saves you some pain.

There are also a few things I want to try but have yet to do them regularly, so I’ll update the post after I’ve experimented with them a bit more. One thing I’d like to try is stretching to aid with digestion, and make it a nightly routine. It seems safe and simple enough to try and implement.

Dietary & Lifestyle Changes

I rarely eat at regular timings, so I’m trying to work on that. I think it’s helped a little, mainly because there is less acid reflux, which can also contribute to irritation along the digestive tract – which includes the esophagus.

The most painful episode for me so far was eating a bag of risotto chips at night, because I thought that rice crackers would be less abrasive and easier to digest than potato or corn chips. I was proved so terribly wrong, as I was up all night coughing and vomiting every 2 hours, and even the entire day after as well. I now have a phobia of anything crunchy, and avoid them especially at night.

Food Textures Matter a Great Deal

I’ve found that foods that are either crunchy or flaky to be the worst, and also anything with lots of ‘specks’ in it, such as black peppercorns.

I probably don’t have to explain ‘crunchy’ to you – stuff like crisps, deep-fried chicken and certain cereals. ‘Flaky’ includes bread, sugary candies like soan papdi (which I love), ginger slices, and basically anything that can be broken down into strips, if that makes sense.

Bread, especially sliced bread with lots of ‘air pockets’ tends to be the worst. This is because they get chewed up into tiny specks that ultimately become trapped in the pouches of the esophageal diverticula. I can feel them tickle at my throat, begging to be spat out. And when they refuse to budge, my body reacts and expels them via vomiting.

The suggestion to ‘eat bland food’ does not appeal to me in the least bit, because I have also developed a phobia after only eating bland food for months on end whenever hospitalised. I call it ‘sick people food’, and the thought makes me depressed. However, the pain and discomfort from the esophageal diverticula means that sometimes, that’s worth the sacrifice.

Avoid Supper at All Costs, if Possible

My sleeping hours are very irregular, as one night of painsomnia can trigger a domino effect for days. So I tend to eat supper, especially if I hadn’t had much to eat earlier on in the day. Whilst the gastroenterologist did say not to eat 2 hours before sleeping, I find that I need to avoid eating right after dinner. It was difficult at first, because my body had been primed to want to eat at night. It’s much better now though. That little change does make a rather big difference.

I did try drinking fruit juice at night as I thought it was categorised as a ‘liquid diet’, but that didn’t work out too well for me at all. The fibre from the fruits tend to be like ‘strings’, so those get trapped in the esophageal diverticula pouches, too. According to Marcin (2024, March 25), such fruits are hard to digest because fibre “isn’t digested by your body”. Whilst the esophagus is technically before the digestive juices start their action, I guess this rule applies too, but in a different way. I’m learning as I go along.

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Foods That are Fine for My Epiphrenic Esophageal Diverticulum

For more substantial meals, soups and stews (including stewed meat and vegetables), work best for me so far. As stews are boiled for a long period of time, this helps to break the food product down partially. In a gross metaphorical sense, they’ve been ‘pre-chewed’ a little to make things easier for you.

I eat less white rice than the average Asian, as it makes me feel quite bloated if I have too much of it. It is still a staple, and apart from bloating, doesn’t cause too much distress. I suppose that’s because they’ve been dehusked and are cooked, making them soft and less fibrous. Noodles and pasta are also okay in general, as once again, I guess it’s because they’ve been cooked at high temperatures.

Other foods I can tolerate with the epiphrenic esophageal diverticulum are: mashed potatoes, eggs, fish, spreads (like jams and compotes), any cooked meat or vegetable, and yoghurt. Things that are okay on the ‘naughty’ food list for me include: ice cream, marshmallow, bingsu (Korean shaved ice dessert), sorbet, jelly and custard.

Foods That Cause Pain for My Epiphrenic Esophageal Diverticulum

Foods that cause me the most pain, in hierarchical order, include: crisps/chips, sliced bread, cookies and biscuits, and high-fibre fruits. Whilst some of these foods can be quite plain, remember that it isn’t so much that your stomach has trouble digesting them. Rather, the pouches from the esophageal diverticula trap some food products more so than others. The time of consumption matters as well. So if I want to try my luck eating one of these food items, it’s safer to try it as early on in the day as possible.

Northwest Minimally Invasive Surgery (2021, April 20) has an information page for patients who have had esophageal or stomach surgery, but the advice is pretty relevant for epiphrenic esophageal diverticulum, too. They state that “it is important that foods consumed be smooth in texture to facilitate the movement of food through the swollen areas of the esophagus or stomach. Bread products that can expand with fluid are avoided entirely”. They also have a list of foods allowed and foods to avoid that makes total sense to me. The list is similar on the Cedars Sinai (2018, May 30) blog about esophageal dietary guidelines as well.

Experimenting with Supplements & Medications for Symptom Relief

I was suffering from two days of bloatedness and regurgitation a while back, and just randomly thought I’d try some magnesium. The justification being that magnesium is an essential mineral for the proper functioning of over 300 enzymes in the body, which includes muscle relaxation and digestion (Al Alawi et al., 2018).

I took a magnesium carbonate effervescent tablet, and was amazed to find that it helped to relieve the epiphrenic esophageal diverticulum symptoms a fair bit. I’m not sure how the esophagus is associated, but hey, it helped with some relief from two days of discomfort. Placebo or not, I’ll take it as a win, and something to add to my pain management toolkit. (I personally like the range of effervescent tablets from Voost.)

However, do note that this ‘trick’ isn’t fail-proof. Half the time it doesn’t work and I still wake up coughing and regurgitating. So I guess the magnesium simply aids with digestion and relaxation in general, which probably has an indirect effect on my body overall.

Interestingly, I did a search about it the next day, and found that magnesium supposedly helps some people who have achalasia. I couldn’t find any papers for it though, as esophageal diverticulum is a rare disease. Healthline has a list of the different types of magnesium supplements, which is interesting general knowledge (Hill, 2023, May 11).

Cough syrup also surprisingly seems to help with the non-stop coughing, even though it’s irritation from the esophagus, instead of the trachea/windpipe. I suppose it suppresses the urge to cough regardless? Having said that, both my parents are having an extremely bad cold and cough at the moment, so perhaps I’ve caught the bug, too. I’ll wait for a couple more weeks before concluding on the cough syrup relief.

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Conclusion on My Personal Experiences with Epiphrenic Esophageal Diverticulum

In sum, epiphrenic esophageal diverticulum is an extremely rare disease with limited research comparatively, so symptom and pain management are mostly through trial and error. Whilst it is not deadly in and of itself unless something rare happens (such as a rupture that will not stop bleeding), it tends to worsen over time. There is also a very small risk of esophageal cancer further down the road. It has definitely ruined my quality of life, especially with the regurgitation whilst sleeping at night. The dietary and lifestyle changes are annoying, because managing my other chronic illnesses is demanding enough.

Whilst I am certainly not looking forward to yet another high-risk surgery in a relatively short span of time, I really hope that I feel better after I recover from it. I’ve read a few Reddit threads on other patients’ experiences with Heller myotomy and fundoplication surgeries, and some of the aftereffects sound really painful and scary. But I guess I don’t really have much of a choice, do I?

If you’ve never had surgery or been chronically ill – the healing process is actually the worst, only because it’s the most boring, painful and helpless period. All you can do is wait for the pain to subside and the wounds to close, which can take months and sometimes, years. But I guess, hope for symptom relief is what keeps me, and others like me, going.

Learn More About the Super Rare Disease – Esophageal Diverticulum

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References:

1. Abdollahimohammad, A., Masinaeinezhad, N., & Firouzkouhi, M. (2014). Epiphrenic esophageal diverticula. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 19(8), 795–797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235103/
2. Al Alawi, A. M., Majoni, S. W., & Falhammar, H. (2018). Magnesium and Human Health: Perspectives and Research Directions. International Journal of Endocrinology, 2018, 9041694. https://doi.org/10.1155/2018/9041694
3. Alicuben, E. T., Luketich, J. D., & Levy, R. M. (2023). Epiphrenic Diverticulum. In Pryor, A. D. & Hawn, M. T. (Eds), Operative Techniques in Foregut Surgery (2nd ed.), 1. Wolters Kluwer Health. Retrieved from https://books.google.com.sg/books?id=xmGvEAAAQBAJ
4. Cedars-Sinai. (2018, May 30). Esophageal Soft Food Diet Guidelines. Cedars-Sinai. https://www.cedars-sinai.org/blog/esophageal-soft-diet-guidelines.html
5. Conklin, J. H., Singh, D., & Katlic, M. R. (2009). Epiphrenic Esophageal Diverticula: Spectrum of Symptoms and Consequences. Journal of Osteopathic Medicine, 109(10), 543–545. https://doi.org/10.7556/jaoa.2009.109.10.543
6. Constantin, A., Constantinoiu, S., Achim, F., Socea, B., Costea, D. O., & Predescu, D. (2023). Esophageal diverticula: From diagnosis to therapeutic management—narrative review. Journal of Thoracic Disease, 15(2), 759–779. https://doi.org/10.21037/jtd-22-861
7. Hill, A. (2023, May 11). 10 Types of Magnesium (and What to Use Each For). Healthline. https://www.healthline.com/nutrition/magnesium-types
8. Hjern, F., Mahmood, M. W., Abraham-Nordling, M., Wolk, A., & Håkansson, N. (2015). Cohort study of corticosteroid use and risk of hospital admission for diverticular disease. British Journal of Surgery, 102(1), 119–124. https://doi.org/10.1002/bjs.9686
9. Marcin, A. (2024, March 25). What Foods Are Easy to Digest? Healthline. https://www.healthline.com/health/easy-to-digest-foods
10. MedlinePlus. (2024, August 27). Fluoroscopy. MedlinePlus. https://medlineplus.gov/lab-tests/fluoroscopy/
11. Northwest Minimally Invasive Surgery. (2021, April 20). Esophageal Soft Food Diet. Northwest Minimally Invasive Surgery. https://www.northwestmis.com/procedure/esophageal-and-stomach/esophageal-soft-food-diet/
12. Sato, Y., Tanaka, Y., Ohno, S., Endo, M., Okumura, N., Takahashi, T., & Matsuhashi, N. (2023). Optimal surgical approaches for esophageal epiphrenic diverticulum: Literature review and our experience. Clinical Journal of Gastroenterology, 16(3), 317–324. https://doi.org/10.1007/s12328-023-01765-2
13. Sudarshan, M., Fort, M. W., Barlow, J. M., Allen, M. S., Ravi, K., Nichols, F., Cassivi, S. D., Wigle, D. A., Shen, R. K., & Blackmon, S. H. (2021). Management of Epiphrenic Diverticula and Short-term Outcomes. Seminars in Thoracic and Cardiovascular Surgery, 33(1), 242–246. https://doi.org/10.1053/j.semtcvs.2020.08.017
14. Whitten, C. (2024, February 20). What to Know About Esophageal Diverticulum. WebMD. https://www.webmd.com/digestive-disorders/esophageal-diverticulum
15. Yam, J., Baldwin, D. L., & Ahmad, S. A. (2023, April 24). Esophageal Diverticula. In StatPearls [Internet]. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK532858/

Why am I Writing About the Rare Disease, Esophageal Diverticulum?

The short answer is because I was recently diagnosed with it, although symptoms have been accumulating for some time now. I had simply assumed that all the regurgitation and vomiting, even in the middle of the night, were due to acid reflux.

If not for an admission to the A&E/ER for something completely unrelated, the doctors would never have found it. The esophageal diverticulum was an incidental finding after I did a CT scan. According to Constantin et al. (2023), “somewhere between 0.06 – 4% [of epiphrenic esophageal diverticulum] are discovered incidentally, radiologically”.

Anyway, I have decided to split this into a two part series. I will publish more about my personal experiences with epiphrenic esophageal diverticulum soon. This post will focus entirely on research I’ve done thus far, as a patient.

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

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A Brief Look at the Esophagus / Oesophagus

In order to understand what certain terms mean and the implications of the different types of esophageal diverticulum, we first need to understand a bit about how the esophagus works. The esophagus is the “hollow, muscular tube that carries food and liquid from your throat to your stomach”, and is part of your digestive system (Cleveland Clinic, 2021b, August 4). It is approximately 9 to 10 inches long (23 to 25 cm).

The esophagus itself is made up of four layers – the mucosa, submucosa, muscularis and adventitia (Yam et al., 2023, April 24), and can be divided into three anatomical segments – cervical, thoracic and abdominal (Chaudhry and Bordoni, 2023, July 24).

Peristalsis

The main function of the esophagus is to transport food from the mouth to stomach, and it does that through a series of muscular contractions known as peristalsis, which is an automatic wave-like movement that happens within the digestive tract (Chaudhry and Bordoni, 2023, July 24; Cleveland Clinic, 2022, April 28).

According to Nehra et al. (2022), “the proximal one-third of the esophagus is composed of striated muscle, the distal one-third is composed of smooth muscle, and the middle one-third contains a mixture of striated and smooth muscle”.

Peristalsis in the different muscle types is controlled by different types of neuronal activity. The lower esophageal sphincter is also made up of smooth muscle segments. This allows for the smooth passing of food into the stomach, and also prevents gastroesophageal reflux (Nehra et al., 2022).

Some other keywords in relation to the esophagus are:

• Esophageal lumen – the inside of the esophagus
• Esophageal sphincter – a ring-shaped muscle that contracts and expands
Mediastinum – The centre area of the chest between the lungs, where the esophagus, heart, thymus, trachea and other structures can be found (Cleveland Clinic, 2022b, August 29)

What is Esophageal Diverticulum?

Esophageal diverticulum is a rare disease with a prevalence of less than 1% globally (Yam et al., 2023, April 24). Patients with esophageal diverticulum have an outpouching within the esophagus, and the disorder is categorised based on anatomical location and type. ‘Diverticula’ is the plural term, where there are more than one diverticulum.

Esophageal Diverticulum Based on Anatomical Location

There are primarily three types of esophageal diverticula – Zenker’s, mid-esophageal and epiphrenic, running from top to bottom of the esophagus (Constantin et al., 2023).

Within the pharyngoesophageal space, they can be further categorised as – Zenker’s, Killian-Jamieson and Laimer’s, once again based on where they occur (Watanabe et al., 2023). Here is a great illustration that shows the differences between these three types of diverticulum, from a left lateral and posterior view (Zakaria and Barawi, 2020).

Then there is also a diffuse type, known as “diffuse intramural pseudodiverticulosis” (DEIPD) (Constantin et al., 2023), which is a “chronic, fibrosing inflammatory disease” (Hentschel, 2022). Iatrogenic diverticulum has also been added as a category recently. As its name suggests, it happens post treatment – peroral endoscopic myotomy (POEM)-type endoscopic therapy, in this instance. Such treatments are often used for late complications of achalasia (a swallowing disorder) (Constantin et al., 2023).

Whilst esophageal diverticulum is a rare disease, the most common tends to be Zenker’s diverticulum – the one that occurs at the top of the esophagus. Esophageal diverticula are also more commonly found in the elderly, and in men as opposed to women (Yam et al., 2023, April 24), so I guess that makes me one lucky dark unicorn again.

Esophageal Diverticulum by Type

There are two ways that an esophageal diverticulum forms – pulsion or traction, with the former being more common. ‘Pulsion’ simply means pushing, whilst ‘traction’ means pulling. Therefore, pulsion diverticula push against the esophageal wall, whereas traction diverticula are ‘sucked in’, which lead to the formation of indentations in the esophageal wall (Cleveland Clinic, 2023, September 29).

According to Sato et al. (2019), pulsion esophageal diverticula form due to “inadequate relaxation of either the upper esophageal sphincter (UES) or the lower esophageal sphincter (LES), causing an increase of intraluminal pressure resulting in a herniation of the esophageal wall in an area of low parietal resistance”. Traction esophageal diverticula on the other hand, involves “adhesion and traction on the esophageal wall in the presence of a mediastinal inflammatory focus, resulting in the formation of a diverticular pouch”.

To simplify that explanation, a pulsion esophageal diverticulum is due to pressure within the esophagus. This leads to an abnormal bulge in the weaker areas of the esophageal wall. Traction esophageal diverticulum on the other hand, is caused by inflammation within the mediastinum. This pulling effect leads to the formation of pouches within the esophagus.

True Versus False Diverticula

Esophageal diverticulum can be further classified as either ‘true’ or ‘false’. According to Yam et al. (2023, April 24), true diverticula involve all four layers of the esophageal wall, whereas only the mucosa and submucosa layers are involved in false diverticula.

True diverticula are caused by traction (pulling), whilst false diverticula by pulsion (pushing). In general, Zenker’s and epiphrenic diverticula are false diverticula, whilst mid-esophageal diverticula are true diverticula.

Some Charts for Easier Digestion (Pun Not Quite Intended)

You can view the correlation between esophageal typography, anatomo-clinical criteria and etiopathogeny in Table 2 here (Constantin et al., 2023).

Figure 1 in this paper by Sudarshan and Murthy (2021) also provides an excellent summary of the three main types of esophageal diverticula. It includes their varying pathophysiology, presentations, work-up and management for easy comparison.

Finally, you can view some images of how various esophageal diverticula look like on Radiopaedia (Rezaee, 2024, December 17).

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Esophageal Diverticulum Symptoms – From Mild to Severe

According to Sato et al. (2023), the main symptoms of esophageal diverticulum are “dysphagia, regurgitation, weight loss, heartburn, respiratory complaints, and retrosternal pain when swallowing food”.

The ‘milder’ symptoms of esophageal diverticulum include an irritating sensation in the throat as if something is stuck there, a sore throat and halitosis (bad breath). As the diverticulum increases in size over time, it can lead to other complications as food gets stuck in the pouches. For instance, patients can get “esophagitis, bleeding from ulceration, impaction, and stasis with regurgitation” (Sato et al., 2023).

Aspiration pneumonia can also happen especially when a person is asleep, where regurgitated food gets inhaled into the lungs and becomes infected. Apart from gastric content, the aspirated fluid can also consist of oropharyngeal secretions and particulate matter (Sanivarapu et al., 2024, March 20).

Aspiration pneumonia is also one of my biggest fears, as regurgitation at night is one of my main symptoms. According to Thomas et al. (2001), other serious manifestations of esophageal diverticulum include: “acute dyspnoea and stridor from pulmonary displacement, cardiac tachydysrhythmias from atrial compression and diverticular rupture, and, rarely, tension pneumothorax”.

In sum, esophageal diverticulum can potentially affect your heart, lungs, and their surrounding structures, due to pressure and/or rupture. It can also give rise to heart rhythm issues.

Whilst the formation of ulcers rarely leads to perforation or bleeding, such events can be life-threatening if they do happen. In addition, atypical symptoms of esophageal diverticulum may remain unknown until surgery is being done (Thomas et al., 2001).

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Diagnosing Esophageal Diverticulum

After that incidental finding of the esophageal diverticula from the CT scan, I had to go for a barium swallow test. The surgeon has also mentioned that I will need to do a manometry and endoscopy as pre-operative procedures.

This is in line with what I have read up thus far within the medical literature. According to Herbella and Patti (2012), the preoperative workup for esophageal diverticulum treatment includes: a barium swallow test, endoscopy, manometry, and pH monitoring if deemed necessary (also see: Thomas et al., 2001).

Let’s take a look at these tests used to diagnose esophageal diverticulum and motility disorders, to better understand why they’re important.

Barium Swallow Test

In order to clearly see and define the esophageal diverticulum, a barium swallow test (esophagram) (MedlinePlus, 2024a, August 27) is usually carried out first. The patient will be made to drink a chalky liquid at intervals. This helps with the visualisation of the diverticulum by ‘highlighting’ it under fluoroscopy, which is a type of x-ray that shows the movement of organs in real-time (MedlinePlus, 2024b, August 27). From the test, your medical team will then be able to determine the size and location of the diverticulum, and also if they are on the right or left side of the esophagus (Sudarshan et al., 2021).

The information from the barium swallow test is important for determining the course of treatment, and type of surgical method to use. In general, surgery is avoided for asymptomatic patients due to the risks, although some surgeons think that it is still essential, as up to 45% of patients demonstrated aspiration (Sudarshan et al., 2021). Some also think surgery is necessary, due to the “risk of cancerization of the diverticulum mucosa or spontaneous rupture” (Sato et al., 2023).

In addition, a timed barium swallow test is able to detect certain motility disorders such as achalasia, as well as “associated conditions such as dysmotility, hiatal hernia, distal esophageal rings, and reflux” (Sudarshan and Murthy, 2021).

Esophageal Manometry

According to Gyawali et al. (2020), “esophageal manometry is generally considered the gold standard for the diagnosis of motility disorders”. It is important to get this diagnostic test done especially for epiphrenic esophageal diverticula, as these are often due to an esophageal motility disorder, such as achalasia or diffuse esophageal spasm (Alicuben et al., 2023).

The word “manometry” simply means a measurement of pressure. A tube will be placed down your nasal cavity and into your esophagus. Thereafter, you will be made to swallow water and/or other liquids of different consistencies, in various bodily positions (Cleveland Clinic, 2023, October 5).

A high-resolution manometry is usually recommended, based on the latest research (Sato et al., 2019). The difference between a regular and high-resolution manometry is that the latter uses more catheters (36 as opposed to 5), thus producing more accurate results (Yadlapati, 2017).

Upper Endoscopy (Esophagogastroduodenoscopy)

A preoperative upper endoscopy is essential for several reasons. First, to rule out other possible diseases (such as Barrett’s esophagus) or malignancies (cancers), and also to clear any debris stuck in the diverticula before surgery is done (Alicuben et al., 2023; Herbella and Patti, 2012).

The Importance of Differential Diagnosis and Detection of Motility Disorders

There are a number of other disorders that can mimic an esophageal diverticulum, and vice versa. A differential diagnosis is essential to rule out such cases. This is simply a process that takes into account all possible diagnoses based on your individual symptoms, medical history, lifestyle and more (MedlinePlus, 2023, February 27). Additional tests may be done if deemed necessary. This helps your medical team to conclude with a more definitive diagnosis, and therefore, the treatment course to take.

For epiphrenic esophageal diverticulum, the differential diagnosis includes: “hiatal hernia, esophageal webs and strictures, esophageal duplication cyst, and esophageal carcinoma”. Other differential diagnosis of underlying causes should also be ruled out as well, such as: “achalasia, distal esophageal spasm, ineffective esophageal motility, esophagogastric junction outflow obstruction, end-stage gastroesophageal (GE) reflux disease with a “burnt out” esophagus, peptic stricture, or failed previous fundoplication” (Alicuben et al., 2023).

Whilst rare, it is also important to screen for malignancies (cancers). The incidence of malignancies from esophageal diverticula is 0.3% to 7% for pharyngoesophageal (which includes Zenker’s), 1.8% for midesophageal, and 0.6% for epiphrenic (Herbella and Patti, 2012).

The Link Between Motility Disorders and Esophageal Diverticulum

As mentioned, motility disorders are often the underlying cause of esophageal diverticulum – particularly so in epiphrenic esophageal diverticulum. In fact, according to Thomas et al. (2001), one should still “remain suspicious” even if a motility disorder is not detected during medical investigations, as apart from achalasia, most of such disorders “occur intermittently and may not be evident during oesophagoscopy, contrast radiology or standard manometry”.

Studies have also shown that “more than 75% of epiphrenic diverticula occur concomitantly with esophageal motility disorders” (Sato et al., 2019). In one small study by Nehra et al. (2002), all their patients with epiphrenic esophageal diverticulum were found to have a motility disorder, using 24-hour ambulatory motility testing.

Achalasia – The Most Common Motility Disorder Found in Esophageal Diverticulum

Achalasia has been mentioned numerous times in this post. Achalasia is a rare swallowing disorder that stems from damaged nerves in the esophagus, specifically in the lower esophageal sphincter. As a result, food and liquid are unable to move down to the stomach. How achalasia develops is still unknown, but has been purported to be autoimmune in nature (Cleveland Clinic, 2021a, April 6).

There are also different types of achalasia based on manometric patterns, namely: type 1 (classic), type 2, and type 3 (spastic). Type 1 achalasia has “minimal contractility in the esophageal body”, Type 2 has “intermittent periods of panesophageal pressurization”, and Type 3 has “premature or spastic distal esophageal contractions”. They also vary in immunohistochemical markers and histology (Patel et al., 2017).

Achalasia is also the most common motility disorder found in patients with esophageal diverticulum (Herbella and Patti, 2012). However, this is not the case in reverse. Less than 5% of patients with achalasia develop an epiphrenic esophageal diverticulum, with the exception of those with ‘vigorous’ achalasia, as more pulsion forces are involved (Thomas et al., 2001).

Diffuse Esophageal Spasm and Other Motility Disorders

The second most common motility disorder found in patients with epiphrenic esophageal diverticulum is diffuse esophageal spasm (Herbella and Patti, 2012). This is characterised by “simultaneous, uncoordinated, or rapidly propagated contractions that are of normal amplitude and accompanied by dysphagia”. Once again, differential diagnosis is critical because there is a long list of disorders that resemble it (Goel and Nookala, 2023, July 2).

In one small study using high-resolution impedance manometry, other motility disorders associated with esophageal diverticulum include, in descending order of occurrence: esophagogastric junction outflow obstruction, jackhammer esophagus, ineffective esophageal motility and absent contraction (Yuan et al., 2024). Another small study by Carlson et al. (2016), which also used high-resolution manometry, revealed “propagating peristalsis, often with hypercontractility” as the predominant motility pattern in their participants.

I would recommend reading this paper by Nehra et al. (2022), which has some insightful explanations of the different types of motility disorders. There are tables which detail how they appear on diagnostic tests, their differentiating features, and the recommended examinations and treatments.

It is also important to note that motility disorders can stem from different dysfunctions. For instance, it could arise from an autoimmune disease (e.g. Scleroderma), impaired inhibitory innervation (e.g. distal esophageal spasm), or excessive cholinergic stimulation (e.g. hypercontractile/jackhammer esophagus) (Nehra et al., 2022).

In sum, it is important to be sure that what you have is truly an esophageal diverticulum, as the treatment and management plan can be quite different for each diagnosis. And since a motility disorder is often the underlying cause of epiphrenic esophageal diverticulum, it is important to investigate this further in order to reduce or eliminate the chance of recurrence.

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Esophageal Diverticulum Treatments

According to Varghese et al. (2007), “optimal surgical treatment is debated, mortality being 9% in the largest reported surgical series of 33 patients”. That’s not much data to go on. For epiphrenic esophageal diverticulum, the ‘traditional’ methods of treatment include: “transthoracic resection, long esophagomyotomy, and an antireflux procedure” (Varghese et al., 2007).

I won’t deep-dive into each treatment type here because honestly, I’m probably as clueless as you are. I think I’ve done sufficient research to ask my surgeon the questions I need to ask however, and his answers convince me that he knows what he is doing. So I will share only the treatments that piqued my interest initially, and also what I would personally need.

Diverticulum Peroral Endoscopic Myotomy (D-POEM)

I had read that diverticulum peroral endoscopic myotomy (D-POEM) is becoming more popular as a surgical method for esophageal diverticulum. It is a minimally-invasive procedure with various adaptations, but generally involves steps to create tunnels, dissect and reseal certain parts of the esophagus and its related muscles (Wang et al., 2020).

I was interested in D-POEM, because studies have shown that it has a high technical and clinical success rate, and also a low recurrence rate. It is also commonly used to treat achalasia and other motility disorders (Pelton et al., 2024). However, it has mostly been used for Zenker’s diverticulum, as compared to other types of diverticula (Mavrogenis and Bazerbachi, 2023).

In any case, I asked my surgeon about it. I didn’t quite understand his explanation of why it wouldn’t make sense to use it. He did say that the surgical treatment that I’d need would be the same regardless of diverticulum type however, which is a Heller myotomy.

Heller Myotomy and Fundoplication

Heller myotomy is the standard procedure used to treat achalasia, where the lower esophageal sphincter is cut to relieve pressure, so that food and liquid can pass through. Acid reflux can occur after a Heller myotomy, so a partial fundoplication may be done in addition (UCLA Health, n.d.).

A fundoplication is an anti-reflux surgical procedure, where a “gastric fold is wrapped around the distal esophagus which enforces the lower esophageal sphincter and prevents gastroesophageal reflux”. It can be either full (Nissen) or partial (Toupet, Dor or Thal) (Abdrabou et al., 2022, April 1).

A Dor fundoplication takes the frontal approach, whilst a Toupet or Thal fundoplication from the back (Abdrabou et al., 2022, April 1). The most common is a Dor fundoplication, where part of the stomach is wrapped over the front of the esophagus and stitched in place. Nissen fundoplication is rarely advised for patients with achalasia, as it can lead to issues with peristalsis (Northwestern Medicine, n.d.).

My surgeon also said that he would probably need to perform the surgery at two entry points, with one incision from near the abdomen. Since my right chest wall has been tunnelled through before in order to repair my mitral valve, a thoracic surgeon will be needed on the surgical team to help ‘navigate’ through the web of adhesions.

According to Torres-Villalobos and Martin-del-Campo (2013), “myotomy can be safely performed using open abdominal and thoracic approaches, and for more than two decades, it has also been done using laparoscopy and thoracoscopy”. I’m assuming that was what the surgeon meant when he was explaining it to me.

Potential Surgical Complications

The rate of symptom relief for esophageal diverticulum is between 85% to 100%, using standard treatments such as “laparoscopic myotomy, diverticulectomy, and fundoplication”. Having said that, the complication rate for the procedure itself is high (Herbella and Patti, 2012).

Some complications that can occur post-surgery include: “air leaks, septicemia and/or sepsis, mediastinitis, mediastinal empyema with or without fistula, mediastinal abscess, postoperative wound infection, and postoperative hemorrhage” (Onwugbufor et al., 2013).

Leaks are one of the more common complications post surgery, at a rate of up to 23%. My own surgeon has told me that a leak was his biggest concern. The mortality rate for the procedure reaches up to 7% as well (Herbella and Patti, 2012).

Your surgeon will most likely use a combination of procedures in order to treat you, based on several factors. Your individual anatomy needs to be accounted for, as well as the size and position of the esophageal diverticulum, comorbidities and more. Each surgical method has its own risks and merits. For instance, a left thoracotomy provides good access to an epiphrenic diverticulum, but is also associated with a high morbidity rate (up to 21% of patients had a leak), and a mortality rate of up to 11% (Herbella and Patti, 2012).

Here is a summarised table of optimal surgical treatments used to treat epiphrenic esophageal diverticulum from 17 published series (Sato et al., 2023).

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Conclusion – There is Still So Much More to Learn About Esophageal Diverticulum

I hope that this article has given you some insight into the rare disease, esophageal diverticulum. I talked about epiphrenic esophageal diverticulum a little more, as that has a direct impact on me.

Doing research has helped me to cope with the helplessness and numbness I am currently feeling. Whenever I discover a correlation between my symptoms and an explanation from a medical journal, I feel enlightened or triumphant. To say that “knowledge is power” is underrated. Knowledge is healing. And we don’t know enough as it stands.

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References:

1. Abdollahimohammad, A., Masinaeinezhad, N., & Firouzkouhi, M. (2014). Epiphrenic esophageal diverticula. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 19(8), 795–797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235103/
2. Abdrabou, A., Kusel, K., & Knipe, H. (2022, April 1). Fundoplication. Radiopaedia. https://doi.org/10.53347/rID-35706
3. Alicuben, E. T., Luketich, J. D., & Levy, R. M. (2023). Epiphrenic Diverticulum. In Pryor, A. D. & Hawn, M. T. (Eds), Operative Techniques in Foregut Surgery (2nd ed.), 1. Wolters Kluwer Health. Retrieved from https://books.google.com.sg/books?id=xmGvEAAAQBAJ
4. Carlson, D. A., Gluskin, A. B., Mogni, B., Koo, J., Sood, R., Lin, Z., & Pandolfino, J. E. (2016). Esophageal diverticula are associated with propagating peristalsis: A study utilizing high-resolution manometry. Neurogastroenterology & Motility, 28(3), 392–398. https://doi.org/10.1111/nmo.12739
5. Chaudhry, S. R., & Bordoni, B. (2023, July 24). Anatomy, Thorax, Esophagus. In StatPearls [Internet]. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK482513/
6. Cleveland Clinic. (2021a, April 6). Achalasia: A Disorder of the Esophagus. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/17534-achalasia
7. Cleveland Clinic. (2021b, August 4). Esophagus. Cleveland Clinic. https://my.clevelandclinic.org/health/body/21728-esophagus
8. Cleveland Clinic. (2022a, April 28). Peristalsis. Cleveland Clinic. https://my.clevelandclinic.org/health/body/22892-peristalsis
9. Cleveland Clinic. (2022b, August 29). Mediastinum. Cleveland Clinic. https://my.clevelandclinic.org/health/body/24113-mediastinum
10. Cleveland Clinic. (2023a, September 29). Esophageal Diverticulum. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/16977-esophageal-diverticulum
11. Cleveland Clinic. (2023b, October 5). Esophageal Manometry Test. Cleveland Clinic. https://my.clevelandclinic.org/health/diagnostics/4952-esophageal-manometry-test
12. Constantin, A., Constantinoiu, S., Achim, F., Socea, B., Costea, D. O., & Predescu, D. (2023). Esophageal diverticula: From diagnosis to therapeutic management—narrative review. Journal of Thoracic Disease, 15(2), 759–779. https://doi.org/10.21037/jtd-22-861
13. Goel, S., & Nookala, V. (2023, July 2). Diffuse Esophageal Spasm. In StatPearls [Internet]. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK541106/
14. Gyawali, C. P., Carlson, D. A., Chen, J. W., Patel, A., Wong, R. J., & Yadlapati, R. H. (2020). ACG Clinical Guidelines: Clinical Use of Esophageal Physiologic Testing. Official Journal of the American College of Gastroenterology | ACG, 115(9), 1412. https://doi.org/10.14309/ajg.0000000000000734
15. Hentschel, F. (2022). Chronic fibrosing esophagitis with diffuse esophageal intramural pseudo-diverticulosis. JGH Open, 6(5), 287–291. https://doi.org/10.1002/jgh3.12750
16. Herbella, F. A. M., & Patti, M. G. (2012). Modern pathophysiology and treatment of esophageal diverticula. Langenbeck’s Archives of Surgery, 397(1), 29–35. https://doi.org/10.1007/s00423-011-0843-2
17. Hjern, F., Mahmood, M. W., Abraham-Nordling, M., Wolk, A., & Håkansson, N. (2015). Cohort study of corticosteroid use and risk of hospital admission for diverticular disease. British Journal of Surgery, 102(1), 119–124. https://doi.org/10.1002/bjs.9686
18. Mavrogenis, G., & Bazerbachi, F. (2023). Peroral endoscopic myotomy for Zenker’s diverticulum without tunneling. Endoscopy, 55, E946–E948. https://doi.org/10.1055/a-2127-7402
19. MedlinePlus. (2024a, August 27). Barium Swallow. MedlinePlus. https://medlineplus.gov/lab-tests/barium-swallow/
20. MedlinePlus. (2024b, August 27). Fluoroscopy. MedlinePlus. https://medlineplus.gov/lab-tests/fluoroscopy/
21. MedlinePlus. (2023, February 27). Differential Diagnosis: Test. MedlinePlus. https://medlineplus.gov/lab-tests/differential-diagnosis/
23. Nehra, D., Lord, R. V., DeMeester, T. R., Theisen, J., Peters, J. H., Crookes, P. F., & Bremner, C. G. (2002). Physiologic Basis for the Treatment of Epiphrenic Diverticulum. Annals of Surgery, 235(3), 346–354. https://journals.lww.com/annalsofsurgery/abstract/2002/03000/physiologic_basis_for_the_treatment_of_epiphrenic.6.aspx
24. Nehra, A. K., Sheedy, S. P., Johnson, C. D., Flicek, K. T., Venkatesh, S. K., Heiken, J. P., Wells, M. L., Ehman, E. C., Barlow, J. M., Fletcher, J. G., Olson, M. C., Bharucha, A. E., Katzka, D. A., & Fidler, J. L. (2022). Imaging Review of Gastrointestinal Motility Disorders. RadioGraphics. https://doi.org/10.1148/rg.220052
25. Northwestern Medicine. (n.d.). Heller Myotomy. Northwestern Medicine. Retrieved 22 January 2025, from https://www.nm.org/conditions-and-care-areas/treatments/heller-myotomy
26. Onwugbufor, M. T., Obirieze, A. C., Ortega, G., Allen, D., Cornwell, E. E., & Fullum, T. M. (2013). Surgical management of esophageal diverticulum: A review of the Nationwide Inpatient Sample database. Journal of Surgical Research, 184(1), 120–125. https://doi.org/10.1016/j.jss.2013.05.036
27. Patel, D. A., Lappas, B. M., & Vaezi, M. F. (2017). An Overview of Achalasia and Its Subtypes. Gastroenterology & Hepatology, 13(7), 411–421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572971/
28. Pelton, M., Kahaleh, M., & Tyberg, A. (2024). Peroral Endoscopic Myotomy for the Management of Esophageal Diverticula: Tunneling Forward. Techniques and Innovations in Gastrointestinal Endoscopy, 26(1), 56–67. https://doi.org/10.1016/j.tige.2023.12.003
29. Rezaee, A., Niknejad, M., & Weerakkody, Y. (2024, December 17). Epiphrenic diverticulum. Radiopaedia. https://doi.org/10.53347/rID-20707
31. Sanivarapu, R. R., Vaqar, S., & Gibson, J. (2024, March 20). Aspiration Pneumonia. In StatPearls [Internet]. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK470459/
32. Sato, H., Takeuchi, M., Hashimoto, S., Mizuno, K., Furukawa, K., Sato, A., Yokoyama, J., & Terai, S. (2019). Esophageal diverticulum: New perspectives in the era of minimally invasive endoscopic treatment. World Journal of Gastroenterology, 25(12), 1457–1464. https://doi.org/10.3748/wjg.v25.i12.1457
33. Sato, Y., Tanaka, Y., Ohno, S., Endo, M., Okumura, N., Takahashi, T., & Matsuhashi, N. (2023). Optimal surgical approaches for esophageal epiphrenic diverticulum: Literature review and our experience. Clinical Journal of Gastroenterology, 16(3), 317–324. https://doi.org/10.1007/s12328-023-01765-2
34. Sudarshan, M., Fort, M. W., Barlow, J. M., Allen, M. S., Ravi, K., Nichols, F., Cassivi, S. D., Wigle, D. A., Shen, R. K., & Blackmon, S. H. (2021). Management of Epiphrenic Diverticula and Short-term Outcomes. Seminars in Thoracic and Cardiovascular Surgery, 33(1), 242–246. https://doi.org/10.1053/j.semtcvs.2020.08.017
35. Sudarshan, M., & Murthy, S. (2021). Esophageal Motility Disorders and Diverticula: Physiologic Implication and Surgical Considerations. Foregut, 1(3), 263–267. https://doi.org/10.1177/26345161211045613
36. Thomas, M. L., Anthony, A. A., Fosh, B. G., Finch, J. G., & Maddern, G. J. (2001). Oesophageal diverticula. BJS (British Journal of Surgery), 88(5), 629–642. https://doi.org/10.1046/j.1365-2168.2001.01733.x
37. Torres-Villalobos, G., & Martin-del-Campo, L. A. (2013). Surgical Treatment for Achalasia of the Esophagus: Laparoscopic Heller Myotomy. Gastroenterology Research and Practice, 2013(1), 708327. https://doi.org/10.1155/2013/708327
38. UCLA Health. (n.d.). Esophageal Health – Esophageal / Heller Myotomy. UCLA Health. Retrieved 22 January 2025, from https://www.uclahealth.org/medical-services/gastro/esophageal-health/tests-treatments/surgical/esophageal-heller-myotomy
39. Varghese, T. K., Marshall, B., Chang, A. C., Pickens, A., Lau, C. L., & Orringer, M. B. (2007). Surgical Treatment of Epiphrenic Diverticula: A 30-Year Experience. The Annals of Thoracic Surgery, 84(6), 1801–1809. 10.1016/j.athoracsur.2007.06.057
40. Wang, S., Chai, N., & Linghu, E. (2020). Diverticulum Peroral Endoscopic Myotomy (D-POEM). In Linghu, E. (Ed.), Therapeutics of Digestive Endoscopic Tunnel Technique (pp. 121–124). Springer. https://doi.org/10.1007/978-981-15-1998-7_9
41. Watanabe, Y., Taniyama, Y., Koseki, K., Ishida, H., Ozawa, Y., Okamoto, H., Sato, C., Unno, M., & Kamei, T. (2023). Distinguishing Killian–Jamieson diverticulum from Zenker’s diverticulum. Surgical Case Reports, 9(1), 21. https://doi.org/10.1186/s40792-023-01599-7
42. Yadlapati, R. (2017). High Resolution Manometry Vs Conventional Line Tracing for Esophageal Motility Disorders. Gastroenterology & Hepatology, 13(3), 176–178. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439137/
43. Yam, J., Baldwin, D. L., & Ahmad, S. A. (2023). Esophageal Diverticula. In StatPearls [Internet]. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK532858/
44. Yuan, M.-C., Chou, C.-K., Chen, C.-C., Wang, H.-P., Wu, J.-F., & Tseng, P.-H. (2024). Characteristics of Esophageal Motility and Associated Symptom Profiles in Patients with Esophageal Diverticulum: A Study Based on High-Resolution Impedance Manometry. Digestive Diseases and Sciences, 69(2), 510–520. https://doi.org/10.1007/s10620-023-08196-6
45. Zakaria, A., & Barawi, M. (2020). Endoscopic treatment of Killian-Jamieson diverticulum using submucosal tunneling diverticulotomy technique. VideoGIE, 5. https://doi.org/10.1016/j.vgie.2020.05.031

Introduction to MediSearch, a Medical AI Search Engine

You’ve probably asked ChatGPT, Gemini or another AI-powered chatbot a medical or health-related question before. Perhaps to try and find a diagnosis, or simply out of curiosity. I have personally asked them some medical questions that I already knew the answers to, simply to see how accurate they were. Google Gemini tends to skirt around health-related issues, whilst ChatGPT gives rather generic answers.

That is not necessarily a bad thing, because the scope of what these AI chatbots cover are quite broad. MediSearch on the other hand, is specifically built to focus on answering medical questions. Thus, you could say that it concentrates all of its resources on health-related topics, to give more detailed and accurate responses.

So when the founder of MediSearch, Eduard, approached me to write an honest review, I was excited to say the least. He also granted me access to the Pro version of MediSearch, so I could test the system and see the differences for myself. Let’s dive into the review – the good and bad (if any)!

*Disclaimer: Whilst this post is sponsored by MediSearch, all opinions expressed in this review are my own. This article is meant for educational purposes and is based on the author’s personal experiences. It is not to be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

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What is MediSearch Exactly, and is It Credible?

MediSearch is a medical AI-powered search engine with over a million users to date. It aims to be the world’s best medical Q&A system. It filters out the noise and only references credible sources and journals – so no random or woo-woo websites. ChatGPT and other AI chatbots are infamous for hallucinating, or to be more harsh, Scientific American straight up says they’re “bullshitting”.

MediSearch on the other hand, cites and links to all sources it derived its answers from. You can click on neatly arranged links to read the medical articles for yourself. If there are no credible sources to be found for your medical question, it will tell you so, or suggest potential questions you might be interested in instead.

One other thing that I love about MediSearch is that it is always up-to-date, so the answers it gives are all based on the latest scientific evidence. Its database is updated within hours of new publications. Even my favourite medical apps, such as MedScape (which I use to check for drug interactions), take weeks to prompt a manual update of medical information. To me, MediSearch truly taps into the power of AI to serve its purpose.

How MediSearch Works

If you’ve ever used ChatGPT or similar, then you know the drill. Simply ask MediSearch a medical question, and it quickly generates the answer with all sources cited. It differs from ChatGPT in the sense that you can’t simply type ‘tell me more’ like in a conversation, but it will suggest possible questions you can follow-up on.

I actually like that it does that, because it doesn’t guess what you’re trying to ask, which can lead you down rabbit holes. For example, I use ChatGPT quite a bit for coding work, but have realised that asking it questions in a conversational style often leads to errors. This is because it infers from the previous text, and amplifies its ‘understanding’ – which can often be false. Specificity is extremely important for medical questions, as it concerns you and your health.

Something else I like about MediSearch is the way its algorithm works. You don’t only get a summary of answers to your medical questions, but one that has been carefully crafted based on ranking factors such as journal quality, number of citations, and more. This means that the answers you’re getting are quality ones.

How Well Does MediSearch Perform for Medical Questions?

According to their website, MediSearch Pro has a 94% accuracy score when tested on the United States Medical Licensing Examination (USMLE) sample examination. The average score for a medical school graduate student taking the exam is 60%. Like me, you might be wondering what the USMLE is exactly, and I took the opportunity to ask MediSearch:

As you can see, the answer that MediSearch generated is comprehensive, and the information is broken down into a readable format that is easy to digest. The USMLE is an important exam that is compulsory for medical students to take, in order to practice medicine in the U.S.

When compared to other AI-powered search engines, MediSearch also had the highest accuracy score for the USMLE sample test, as can be seen from the chart below:

Taking MediSearch for a Test Drive

I decided to ask MediSearch questions I have done extensive research on as a patient, namely Antiphospholipid Syndrome (APS) and Spontaneous Bilateral Patellar Tendon Rupture (SBPTR). These are medical conditions I live with, and have written resources on myself.

Asking MediSearch a Basic Medical Question

I started with a basic question about APS, “What are the lab tests used for diagnosing Antiphospholipid syndrome?”:

This pretty much summarises what took me hours of manual research, in order to include proper references for my APS resource guide. It also highlights that LA is “considered the strongest predictor for adverse pregnancy-related events and thrombosis”. This is an important note, and something my own rheumatologist has pointed out to me before.

Asking MediSearch a More Complex Medical Question

Next, I decided to ask MediSearch about Tecarfarin, which is a blood thinning medication still undergoing clinical trials. It is a drug that is targeted more for heart and kidney disease patients, and less for APS (a blood clotting autoimmune disorder), so I was curious as to what its response would be.

The response provided by MediSearch was well-informed once again, as seen in the screenshot below. It states clearly that Tecarfarin is still limited in evidence for APS, and tells me more about what it is, which stage the clinical trials are at, and more important medical information. This matches up with the research I had done (as a patient) for my article on medications in relation to APS, which took me months to put together.

Who is MediSearch for?

MediSearch isn’t only for medical writers, clinicians, or chronic illness patients who have lived with their diagnoses for years. It is also suitable for ‘everyday’ health questions that the average person may have, such as, “is coffee good for health?”, “best foods for reducing cholesterol”, or even “is breakdancing considered a sport?”. Yes sorry, I just had to ask MediSearch about breakdancing, given the Olympics fiasco 😉

Even for ‘simple’ questions such as these, MediSearch cites its sources. I tried asking ChatGPT 4.0 the same question about coffee, and whilst it provided the potentials and drawbacks, no sources were cited. We are living in an age of information overload, disinformation and misinformation, so it’s even more vital to know where the answers generated come from – which MediSearch does.

Every single source it cites is clickable, and taken from actual medical journals, international health guidelines, published books and other credible sources. Regular AI chatbots on the other hand, are fairly limited when it comes to medical questions, as they are only able to retrieve information from open-access or free/public resources.

P.s. To see what the answer is to: “is breakdancing considered a sport?”, simply type the question into the search box on MediSearch’s website. 🙂

Benefits of MediSearch Pro Version

Increased Number of Sources to Refine Accuracy Further

The answers you have seen in this review thus far are all from the MediSearch Pro version. Whilst the standard version gives concise answers as well, the MediSearch Pro version sources from more medical articles, which further refines accuracy.

A sample from the standard version can be seen from the screenshot below. If you compare this to the other screenshots we have seen thus far, whilst it is still evidence-based and informative, the answers from the Pro version are more detailed and streamlined. For the example question below, “is coffee beneficial for health?” – the standard version cites two references, whereas the Pro version gave me 10.

Advanced Filter Options and Citation Tools

If you use Google Scholar, then I’m sure that you’ve clicked on ‘filter by publication date’ at some point, because you want the latest information about a specific topic. MediSearch Pro has a filter by date feature as well, and you can also select which type of sources you want it to search from, such as “scientific articles” and “books”.

If you are a medical writer or need to compile a list of references, MediSearch Pro’s citation tool comes in handy. I personally gather all my references using Zotero, and the ‘export’ feature in MediSearch Pro is compatible with it, including its browser extension. This will save me so much time for research-based articles I write in future.

Search for Related Insights with a Click of a Button

In addition, the Pro version also allows you to search for more related articles, find contradictions and see what others think. These additional insights are important if you’re doing research – whether for personal or work related purposes.

If you’ve done research for anything at all (shiny objects included), then you know how important perspectives can be. It is good to have all the cards laid out on the table, so that you can make better judgement calls. The “find contradictions” feature to me is a very good one, because it questions the initial answers to see if there may be potential loopholes.

The “see what others think” feature is also quite interesting, although I personally wouldn’t use it much. It essentially peeks into Reddit threads to see what others have been asking or thinking about in relation to your topic.

This may be a personal preference thing however, as I don’t even trust Reddit on a regular day (I may be a millennial…). I do know that many of my Gen Z friends use Reddit more than even Google Search however, so I can see how this is useful. In their own words, “it gives me human, straightforward answers, and not some lengthy blog with a biased opinion”.

Another thing you could potentially do is to see what others are asking or thinking, rephrase it into a specific question, then feed it back into MediSearch to find out what the science actually says.

Other Video Reviews Available on MediSearch Pro by Health Professionals

If you hate to read and prefer to watch a video to see how best to utilise MediSearch Pro, here are some great reviews by medical professionals and/or establishments:

How to Use MediSearch for Your Medical Writing (by Alex Evans, PharmD, MBA):

Dr. Vimalakar Reddy of KIMS-SUNSHINE Hospitals reviews Medisearch AI tool:

More for the Technically-Inclined and Businesses

MediSearch comes with documentation for developers. You will need an API key to integrate MediSearch into your website or app, which can then be used to generate a medical Q&A chatbot.

Medical businesses or establishments can also use MediSearch to benefit both clinicians and patients. For patients, MediSearch Pro can be used to generate evidence-based health tips, based on individual user data. For clinicians, MediSearch can be used to manipulate Electronic Health Records (EHR) for summaries and also in other novel ways.

Conclusion to My MediSearch Review: Would I Get the Pro Version as a Chronic Illness Blogger and Patient?

The answer is a resounding “yes”. I honestly loved how streamlined, concise and accurate the answers were, and the intuitive user interface. If you have been following my blog for a while, you would know that I recently published an APS A – Z resource guide. This resource took me years to complete, and is truly a work-in-progress. There is still a lot of information that I would like to add to it, such as a related article about herbs, foods and drinks to avoid with APS. With MediSearch Pro, I know that the research process will go much quicker this time around, and I’m actually excited to get started again.

I also work as a medical writer for my own clients, on topics such as digital healthcare, orofacial pain, oral medicine, vitamins and more. I spend a lot of time doing manual research for each article, which can take me days or weeks – more than the actual writing itself. I can see how MediSearch Pro will be an asset to my medical writing jobs in future as well.

In addition to the website version, you can also download MediSearch on the Apple or Google app store – just click on the buttons below:

Visit the MediSearch Website
Download MediSearch on the Apple Store
Download MediSearch on the Google Store

Read Related Posts:
• Antiphospholipid Syndrome Diagnosis: The A to Z Guide as a Patient
• Latest Research on Antiphospholipid Syndrome (2024 Edition)
• The Lowdown on Medications and Antiphospholipid Syndrome (Warfarin, Enoxaparin, DOACs, NSAIDs & More)
• Knee Surgery Post-Operative Care: Introduction to the Series
• Why I Need to See 10 Different Doctors on a Regular Basis
• Advice That Could, Quite Literally, Kill

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*Disclaimer: This article is meant for educational purposes and is not a substitute for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. Read our Privacy Policy page for more information. Thank you!

Introduction

From adolescence to motherhood and later stages of life, a woman’s body undergoes remarkable changes. Each phase brings unique challenges, from hormonal and bodily changes during adolescence to the physical and emotional demands of pregnancy and motherhood and, later, the effects of menopause and aging on bone density and energy levels.

Beyond treatment of illnesses, you can also focus on nurturing your mind, body, and spirit at every stage in order to build up a more balance and holistic approach to health and women’s wellness. This post is here to inspire and guide you towards a complete body care routine.

How To Take Care of Your Body

1. Nutrition

A balanced diet forms the foundation for optimal health for women. It’s essential to consume a variety of macronutrients, such as carbohydrates, proteins, and fats, to fuel your body and support its functions. Carbohydrates provide energy, while proteins are crucial for tissue repair and muscle maintenance. Fats from foods like avocados, nuts, and olive oil play a key role in supporting hormonal balance and boosting overall health.

While a balanced diet should ideally supply all your nutrients, certain life stages or dietary restrictions may require supplements. For example, women at risk for osteoporosis might consider calcium and vitamin D to support bone health. As with nutrition, hydration is also essential for overall well-being. Daily water needs vary, but a good sign of adequate hydration is pale and clear urine.

2. Physical Activity and Exercise

Physical activity is essential for women’s wellness, and staying active can lower the risk of mortality and prevent and help manage heart disease, diabetes, and cancer, while also improving brain health and reducing symptoms of depression and anxiety. For pregnant women, physical activity can reduce the likelihood of complications without raising the risk of low birth weight or stillbirth.

Here’s the good news: physical activity covers pretty much anything that gets you moving and burning energy. Whether you’re walking, doing chores, or playing with your kids, it all counts towards better health. For maximum benefits, aim for 150–300 minutes of moderate aerobic exercise or 75–150 minutes of intense activity each week.

Additionally, pelvic floor exercises like Kegel exercise are vital for strengthening the muscles that support the bladder, uterus, and rectum, promoting better core stability and preventing issues such as incontinence.

3. Intimate Health and Wellness

Maintaining intimate hygiene is essential for overall health. Stick to washing the vulva with water and a mild, unscented soap if you want. The vagina cleans itself, so there is no need for extra products; steer clear of harsh soaps, douches, and heavily scented stuff, as they can mess with your natural balance and lead to irritation or infections.

Hormonal changes, especially after childbirth or during menopause, can lead to dryness, discomfort, or changes in how things look and feel down there. For some, these changes can affect confidence and daily comfort. That’s where pelvic floor exercises and vaginal rejuvenation surgery come in, as they can help with issues like muscle tone and laxity! If you’re considering vaginal rejuvenation procedures, consult with a healthcare provider to ensure it’s right for you.

Don’t skip those regular gyno check-ups, either. Pap smears, screenings, and self-exams are essential for catching infections or abnormal growths early.

4. Mental and Emotional Health

Taking care of your body as a woman involves physical health and prioritizing mental and emotional well-being.

Stress management is crucial; techniques like mindfulness, meditation, and breathing exercises can help you stay grounded and reduce anxiety. Engaging in self-care practices is equally important. Activities like journaling, pursuing hobbies, and finding time for relaxation can foster joy and help you recharge. Whether painting, gardening, or reading a book, making time for what you love can significantly boost your mood and resilience.

Finally, it is vital to recognize the importance of mental health resources. Therapy and counseling can provide essential support, especially during challenging times. Be aware of signs that it might be time to seek help, such as persistent feelings of sadness, overwhelming stress, or difficulty coping with daily life.

5. Skin and Hair Care

Your 20s are a great time to start a skincare routine and develop healthy habits for your skin. But if you’re past that age, don’t worry It’s never too late to begin! Your skincare routine should match your skin type, age, and specific concerns. But the essentials are simple: start with a gentle cleanser that works for you, follow up with a moisturizer to hydrate and protect your skin, and don’t forget sunscreen with at least SPF 30 whenever you head outside.

Add some science-backed ingredients if you want to level up your routine and address specific concerns. Retinoids are awesome for tackling fine lines and wrinkles, while vitamin C helps fade dark spots and signs of aging. Ceramides boost your skin barrier, and peptides help your skin produce more collagen.

Knowing your hair type helps you choose products that actually work, whether your hair is curly, straight, exemplary, or thick. Shampoo is based on how frequently your hair gets oily or dirty, focusing on the scalp to avoid drying out the strands. Make sure to follow up with the conditioner every time to detangle and moisturize.

Be gentle, especially with wet hair. Detangle using a wide-tooth comb, starting from the ends and working up, and try wrapping your hair in a towel or t-shirt instead of rubbing it dry. Limit heat styling, and always use a heat protectant if you do.

Key Takeaways and Final Thoughts

A holistic approach to body care is significant because it recognizes the interconnectedness of physical, mental, and emotional health, allowing women to thrive in all areas of life.

Remember, taking care of yourself is essential for living a balanced and fulfilling life. It enables you to navigate challenges with confidence and joy. Embrace this journey of self-care and make it a rewarding part of your everyday routine.

Read Related Posts:
• Pregnancy, Miscarriage & Women’s Health in Antiphospholipid Syndrome
• After Surgery Care at Home: Hygiene Resources
• How to Use the 7 Dimensions of Wellness to Thrive with Chronic Pain

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Contributor Bio

Dr. Ammar Mahmoud is a renowned OB-GYN who specializes in minimally invasive cosmetic gynecology, offering advanced procedures to enhance sexual wellness. A sought-after speaker, he is dedicated to providing innovative, compassionate care that boosts confidence and well-being.

All of my recent posts have been extremely ‘heavy’, so to speak. First, there were the two knee injury series – one on resources for post knee surgery, and the other on things you can do whilst bed bound. Then, there was the Antiphospholipid Syndrome A to Z resource, which included a few other topics such as medications, women’s health, the latest APS research and all the major organs in the body that the autoimmune disease can hit.

Researching and writing those articles consumed a lot of my brain power and energy, which comes in limited edition as a person with multiple chronic illnesses. Then, I landed in hospital with more new diagnoses just a few weeks after school re-opened…..

…Or Maybe It Just Needs More Darkness!

So I decided to do this post for a bit of fun, and to take a break from the dreariness of it all. A metaphorical digestif, if you will. This post is part of a TikTok trend (I should really get on it some time soon, shouldn’t I?), “Tell Me Without Telling Me”. I learned about it from a post by Caz over at invisiblyme.com, although I can’t seem to find the original post now. Many of us who live with chronic illness endure our days with chronic pain, chronic fatigue, brain fog and other unnameable unpleasantries.

Humour has always carried me through the darkest periods of chronic illness, especially when faced with mortality. Morbid, dark humour is my favourite. It somehow lightens the whole situation, and makes things seem less scary or foreboding. To be able to laugh into the face of death takes away some of its power, and lightens the load. It gives me the strength to carry on.

What about you? What sort of humour do you enjoy the most, and does it help you through the dark days? Check out these “Tell Me You’re Chronically Ill Without Telling Me You’re Chronically Ill” memes I made, and let me know if you can relate to any of them in the comments below!

Read Related Posts:
• Chronic Illness Quotes to Inspire, Motivate, Grieve, Hope & Laugh About
• 12 Visible Evidence of a Body Gone Rogue (Is Invisible Illness Truly Invisible?)
• How to Use the 7 Dimensions of Wellness to Thrive with Chronic Pain
• 7 Reminders For Those Bad Days to Keep You Going
• An Open Letter to Death, and One Simple Plea

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Updated: 20 March 2025 – More memes added at the bottom of the page.

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

“Tell Me You’re Chronically Ill Without Telling Me You’re Chronically Ill” Memes – Can You Relate?

1. Autocorrect keeps ‘correcting’ your medical words to something incorrect. No way you actually meant “antiphospholipid” or “encephalomyelitis”.

2. Sometimes you wish you were older, just so people would stop questioning the reality of your illnesses because you’re ‘too young’ to be that sick.
3. You drill your travel companions on emergency protocols like an army sergeant, just in case you get a seizure or something cool.
4. Superfoods and kale juice can land you in the A&E/ER at best, or kill you at worst.
   
5. Your girlie pouch in the bag contains emergency medication (make that medicationS). Maybe lipstick and mascara – if there’s space.
6. You can read a medical article in a minute and actually understand all the jargon.
7. Choosing the ‘physician’ rather than ‘consumer’ version of medical articles to read.
   
8. Spontaneity means getting prepared to be spontaneous. Unless of course, it’s a trip to the ER.
   
9. You also have a ‘grab and go’ bag even though you’re not pregnant, for that said spontaneous trip to the A&E.
10. Also, you don’t just have a backup plan, but the backup plans.
    
11. When the #1 item on your Christmas wish list is simply – less pain. (A girl/boy can dream?)
    
12. Your hands have a ‘daily quota’, so you use other body parts to compensate. Hey, shoulders are more efficient for opening doors, non?
13. Gross isn’t gross – it’s important medical information that needs to be described in great detail to doctors so they can diagnose you properly and relieve you of pain.
    
14. You develop naked body confidence, after needing to undress or spread your legs for the doctor/lab tech/whichever medical professional for the umpteeth time. It’s just a body.
    
15. You need to dismantle your sushi because you can’t open your mouth wide enough to take a bite.
    
16. Cutting up steak also requires careful planning and execution. If in company or if your hands are too painful for the day – abort mission and order a miserly salad like you meant to instead.
17. That said, you can knock back a fistful of pills like a pro. They should really have a Major League Eating Pill Popping championship, because you would totally rock that.
18. You also have a ‘pill swallowing method’ where various parts of your mouth cavity serve as storage and launching devices.
19. You have chronically ill internet friends who ‘get you’ more than people in real life. These are people you can discuss body parts, bowel movements and pain with all day without judgement.
    
20. Monitoring your energy levels at events has become second nature, especially after you’ve had to make Titanic drama level exits a couple times.
21. A shopping spree consists of pyjamas, compression clothing, ice and heat packs, hot water bottles, and mobility aids.
    
22. Your ‘savings’ amount to a grand total of… $0. Those pesky medical bills really need to ease up their enthusiasm for a bit…
    
23. You want to read that 1000-page book but fret, because you know it’s a trade off with pain in your finger and hand joints. (Thank goodness for Kindles!)
24. Essential to do on arriving home from ‘the outside world’ – wiping your phone down with a 70% isopropyl alcohol wipe.
    
25. You glance or glare passive aggressively at anyone who coughs or sneezes on the street (or the elevator…gross).
26. You’re grateful that the pandemic normalised mask-wearing (speaking for Asia, at least).
27. The chemist is like the adult version of a candy store where you restock your OTC supplies.
    
28. When you know the actual medication name – not just the brand name – better than the pharmacist or doctor. No, it’s not just Clexane or Lovenox, it’s enoxaparin to be precise.
29. You run a mini pharmacy at home that takes up at least a few shelves. People come to you for medical supplies for minor ailments, or to ask you what their symptoms could be indicative of.
    
30. That mini pharmacy extends to your bedside table, where you keep emergency supplies for immediate access.
31. When the GP panics just as much as you, and just directs you to the nearest ER.
    
32. You have a weighted blanket to help manage your anxiety… except you regret buying it because it’s basically a giant paperweight when your swollen hands can’t pull it up at night.
33. You hold your bladder in and calculate your toilet breaks like an arithmetic problem, in order to save your knees some pain per trip.
    
34. You also need 5 minutes to mentally prepare yourself just to sit up, when you need to use the toilet at night.
35. You can prattle off tongue-twister medical conditions and medications off the tip of your tongue like poetry.
    
36. Your bottle of concentrated peppermint essential oil has saved a drunk friend or two from puking.
37. You have two homes. The second being the hospital. Even the staff know you by name.
    
38. The fear of boarding public transportation is real. Often you avoid the disabled seat even if no one is sitting in it, for fear of being accused.
39. Same goes for disabled toilets. When you’re actually out with your walking stick or mobility aid, you feel vindicated just standing outside. Look at my mobility aid, goddamnit.
40. Home is where the… medications are.
    
41. Your calendar is fully booked for the rest of the year with doctor appointments. Maybe you can squeeze a friend in somewhere, but probably not.
42. Your handwriting is like a 4 year-old’s scrawl because your hand trembles, either from illness or a medication side effect.
    
43. When you rupture your tendons, but assume it’s ‘just a dislocation’ that your hypermobile friends online can teach you how to pop back.
44. People think you’re cold and arrogant, no thanks to your resting pain face.
    
45. Your idea of a fun, wild night out with friends is chilling on the couch at home, playing board games. Maybe one glass of wine tops, and with a wine wand.
46. You’re absolutely shocked when/if you wake up to a pain free day. You poke and prod your body all day in disbelief, and wonder if that’s how ‘normal’ people feel every day?!
    
47. You now consider work stress as a luxury problem, and dream of being stressed out about work, instead of rotting in bed all day long with pain and fatigue.
    
48. You understand that ‘just be happy’ is a bullshit platitude and attitude on life, when you live in chronic pain. So you seek a life with meaning instead.
    
49. When someone asks if you’ve heard of a disease… You can guess based on its medical name.
    
50. You carry a water bottle wherever you go (with at least one sip left) just in case you need to pop that emergency med.
    
51. You know you have a rare disease when… you search a hashtag on social media, and the ‘latest’ post is yours from 2 years ago.
    
52. You win word games all the time because you know fancy words like… Encephalomyelitis, antiphospholipid, carbamazepine, anaesthesiologist.
    

Conclusion to the “Tell Me You’re Chronically Ill Without Telling Me You’re Chronically Ill” Meme Series

Could you relate to any of these memes as a person with chronic illness or disabilities? I’d love to hear which you could relate to the most in the comments below! And if you have a good chronic illness meme of your own, I’d love to hear it too, and perhaps add it to this post (with credits to you, of course)!

Wishing you a low-pain day, and one filled with laughter 🙂

Read Related Posts:
• Call Me Sick Girl (Or How to Make Your Weakness Your Strength)
• 365 Mindfulness Journaling Prompts for Self-Improvement
• Today is Not a Good Day to Make Decisions (and That’s Okay)
• Would You Rather: Have an Invisible Illness or a Visible Disability?
• “It’s in My Blood”: Featuring People with Illnesses, Passions & Talents

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You may have heard of the rare blood clotting disorder, Antiphospholipid Syndrome, but did you know that it isn’t ‘just’ about the blood? This article is part of the Antiphospholipid Syndrome (APS) resource library that I’m building up on my site from a patient perspective. It consists of findings from research journals, as well as over 20 years of my personal experiences with APS. This post will focus on how does Antiphospholipid Syndrome affect the body, beyond the blood to major organs.

I won’t deep dive into each medical condition, or the post will never end 😉 (Also, I have found anatomy to be my least favourite research topic…but we’ll definitely have to delve a bit into it here!) If I get the motivation in future however, I will write up separate articles for each major organ in relation to Antiphospholipid Syndrome.

If there are terms or topics in this article that you’d like to learn more about, then check out the complete A – Z resource guide and related APS posts below as well!

Read the A – Z Antiphospholipid Syndrome Guide

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

Changelog:
• 14 January 2025: Added new study by Huang et al. (2025) on future atherosclerotic cardiovascular disease in SLE/APS patients.

Read Related Posts in the Antiphospholipid Syndrome Diagnosis Series:
• Latest Research on Antiphospholipid Syndrome (2024 Edition)
• Pregnancy, Miscarriage & Women’s Health in Antiphospholipid Syndrome
• The Lowdown on Medications & Antiphospholipid Syndrome (Warfarin, Enoxaparin, DOACs, NSAIDs & More)
• The Annoying Thing About Living with Antiphospholipid Syndrome (My Personal Experiences)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• What it Feels Like to be Refused Treatment by a Hospital’s A&E / ER

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Antiphospholipid Syndrome is a Systemic Autoimmune Disease

What this means simply (but we know it’s not that simple, is it?), is that it can affect any part of the body in different ways.

According to García-Carrasco et al. (2013):

“The clinical features and laboratory manifestations associated with aPL [antiphospholipid antibodies] have broadened considerably since the first description of APS in 1983 and now include thrombocytopenia, hemolytic anemia, cardiac valve disease, pulmonary hypertension, microangiopathic nephropathy, skin ulcers, livedo reticularis, refractory migraine, cognitive dysfunction, and atherosclerosis.”

Beyond direct blood-related manifestations, Antiphospholipid Syndrome can also affect the heart, lungs, skin, brain and more. People who have an autoimmune disease tend to have comorbidities as well (i.e. those mutations love a party). For one, researchers have found that there is a high risk of developing Systemic Lupus Erythematosus (SLE), especially during the first 5 years of being diagnosed with Antiphospholipid Syndrome (Chen et al., 2021).

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Let’s Get the Bloody Issue Out of the Way First

Patients with Antiphospholipid Syndrome are at an increased risk of blood clots, due to the production of antiphospholipid antibodies (aPLs) that attack phospholipids (Cleveland Clinic, 2022e, August 19). They can cause abnormalities in white blood cells, red blood cells, platelets, and other components of blood both directly or indirectly. Symptoms of blood clots depend on the body part where they’re ‘stuck’ at. Let’s take a look at a few direct manifestations of Antiphospholipid Syndrome within the blood.

Deep Vein Thrombosis (DVT)

Venous thrombosis (VT) is the most common clinical manifestation of Antiphospholipid Syndrome, with up to 30% of APS patients having had an episode (Biggioggero and Meroni, 2010). A VT usually occurs as a deep vein thrombosis (DVT).

You’ve probably heard of DVTs (Reyes and Abe, 2023, May 1), in news articles scattered across the internet especially in relation to long-haul flights (Ward, 2024, April 5), as they can also occur in healthy people as a result of prolonged periods of inactivity. DVTs are blood clots that tend to form in a deep leg vein, although they can occur anywhere in the body. If these clots are large enough, they can also lodge in the brain, heart, lung or heart, which can quickly turn into a life-threatening situation.

Read Related Posts:
• Top Tips for Travelling with Chronic Illness & Disability (From a Girl Who Loves to Travel)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• My Recovery Time for Simultaneous Bilateral Patellar Tendon Rupture (With Lupus & Steroid Treatment)
• My Second Brush with Death: A Broken Heart (Literally)
• Bloody Mutations into Lupus

More About Veins

This article from Cleveland Clinic (2022c, June 19) does a fantastic job of explaining what veins are. To summarise, veins are blood vessels that are an important part of the circulatory system, and 75% of blood in the human body is contained within them.

Apart from the pulmonary veins, they carry oxygen-poor blood back to your heart (arteries carry oxygen-rich blood in reverse). Collectively, they form the venous system, and there are a few different kinds – deep veins, superficial veins and perforating veins. Deep veins are found in the muscles and along bones, and contain 90% of the blood that needs to make its way back to the heart in the legs. That is why it is more common to experience a DVT in the legs.

An interesting anatomy tidbit from Cleveland Clinic – calf muscles are also known as the ‘second heart’ as they help to pump blood back up against gravity. That is why it is important to keep moving and walking on long-haul flights, and why bedbound patients often need to wear compression stockings to prevent a DVT from occurring. Breathing is another important factor in helping blood to circulate.

Thrombocytopenia

Platelets are also known as thrombocytes, and thrombocytopenia is a condition when your platelet count is too low (National Heart, Lung, and Blood Institute, 2022, March 24). This can lead to excessive bleeding, as your blood is unable to clot sufficiently. Thrombocytopenia is also the most common non-criteria manifestation of antiphospholipid antibodies (aPLs), with a frequency of between 20% – 50% (Artim-Esen et al., 2015).

It is recognised as a complication of patients with lupus anticoagulant and anticardiolipin antibodies in particular. Those with APS and SLE concomitantly also exhibit thrombocytopenia with greater frequency. Having said that, thrombocytopenia is usually not severe in APS patients, and usually does not require therapy (Forastiero, 2012).

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The Increased Risk of Cardiovascular Disease in Antiphospholipid Syndrome

Cardiovascular disease (CVD) is an umbrella term that covers disorders of the heart and blood vessels, and is the leading cause of death globally (World Health Organization, n.d.). The usual suspects contribute to CVD, such as smoking and an unhealthy diet. Smoking is also one of the most important predictable risk factors for cardiovascular disease in people with Antiphospholipid Syndrome. The combination is strongly associated with arterial vascular events, especially ischaemic strokes (when a blood clot blocks an artery in the brain) (Tektonidou, 2022; Mayo Clinic, n.d. -b). As such, it is important for people with APS to mediate what they can in an attempt to maintain and improve their overall health.

According to Polytarchou et al. (2020):

“Patients with APS have endothelial dysfunction, accelerated endothelial proliferation and intimal hyperplasia, atherogenesis, platelet activation, inflammatory products secretion and coagulation-fibrinolytic dysregulation.”

All that basically goes to say that APS patients are more prone to CVD, due to thrombotic and inflammatory factors in addition to traditional risk factors. Let’s break that down a bit to make more sense in relation to blood clotting and Antiphospholipid Syndrome.

What is the Endothelium?

Endothelium refers to the thin layer of cells that lines the inside of blood vessels, and endothelial cells secrete substances that control the opening and closing of arteries, which subsequently determines blood pressure and how hard your heart has to pump (Cleveland Clinic, 2022b, May 12). These substances also activate the fibrinolysis system (which helps to regulate blood clots) (MedLine Plus, n.d.), and mediates platelet adhesion and shear stress induced aggregation (Wu and Thiagarajan, 1996).

There are four different types of endothelial cells, namely: arterial, venous, capillary and lymphatic. These cells can be found in major organs, such as the brain, liver, kidney, lungs and heart, where they proliferate (reproduce) at different rates, serve different functions, and vary in movement (Przysinda et al., 2020).

Endothelial Dysfunction & Antiphospholipid Syndrome

According to Stanford Health Care (n.d. -b): “Endothelial dysfunction is a type of non-obstructive coronary artery disease (CAD) in which there are no heart artery blockages, but the large blood vessels on the heart’s surface constrict (narrow) instead of dilating (opening).” Endothelial dysfunction causes chronic chest pain, and is more frequently seen in women than in men.

This dysfunction is usually due to low levels of nitric oxide gas in blood vessel walls, which can trigger inflammation, and other platelet and blood vessel dysregulations. These can result in blood clots, strokes, hypertension, heart attacks, and more.

Patients with APS have been found to have impaired synthesis of nitric oxide that can be caused by various factors. APS patients with thrombosis were found to have low plasma levels of nitrites and nitrates, which are important metabolites for breaking down nitric oxide. Antiphospholipid antibodies also have implications in how nitric oxide synthesises (Velásquez et al., 2018).

Cardiovascular Diseases that APS Patients are More Prone to

According to Tektonidou (2022) and Polytarchou et al. (2020), a few of the types of cardiovascular diseases that patients with Antiphospholipid Syndrome are more prone to include:

1. Hypertension (high blood pressure). Hypertension is a leading cause of death worldwide (World Health Organization, 2023, March 16). It is also one of the most common traditional risk factors for APS patients, where approximately 20 – 35% of APS patients have it. It is also more commonly found in patients with a combination of SLE/APS, as compared to PAPS (Primary Antiphospholipid Syndrome).
2. Pulmonary Hypertension (PH). This is different from ‘regular’ hypertension, as it mainly affects either arteries or veins in the lungs; ‘regular’ hypertension on the other hand, is when there is constriction in your arteries, and can happen anywhere in the body (National Heart, Lung, and Blood Institute, 2023, May 1; Orlando Health, n.d.). People who are positive for antiphospholipid antibodies have been found to be susceptible to all five groups of PH, with those who have a comorbid connective tissue disorder such as Lupus, at a slightly higher risk.
3. Hyperlipidemia (elevated lipids such as cholesterol). Hyperlipidemia is another prevalent medical condition, especially in developed countries that eat a high-fat, Western diet (Cleveland Clinic, 2022d, August 4). It is also another leading cause of cardiovascular disease in patients with Antiphospholipid Syndrome, and is present in about 20% – 25% of patients.

4. Atherosclerosis (hardening of arteries caused by a buildup of plaque). This is a prevalent condition, but many people may not be aware that they have it as they may not have symptoms in the early stages (Cleveland Clinic, 2024a, February 15). Studies have found that atherosclerotic plaques are associated with IgG and anti-β2GPI antibodies, and that APS and/or SLE/APS patients had almost 2.5 fold the risk of them developing in the carotid and/or femoral arteries.

   Another recent study by Huang et al. (2025) also concluded that “SLE patients with positive aPLs, especially positive aCL [anticardiolipin] IgG/IgM and LA [lupus anticoagulant], warrant more care and surveillance of future ASCVD [atherosclerotic cardiovascular disease] events during follow-up”. The study also found that aCL IgA and anti-β2GPI IgA antibodies were independent risk factors for ASCVD, even in participants without autoimmune disease.

5. Acute Coronary Syndromes (ACS). These are a group of disorders that include heart attacks and unstable anginas (chest pain when your heart muscle doesn’t get enough oxygen-rich blood), and is a medical emergency when it happens. ACS most commonly happens due to a plaque bursting, or when a blood clot blocks blood flow to the heart (Cleveland Clinic, 2022a, May 2; Cleveland Clinic, 2024c, May 24).

   Patients with Antiphospholipid Syndrome have an increased risk of ACS, which can happen even with normal or non-obstructive coronary artery disease, or with normal or near-normal coronary arteries (Stanford Health Care, n.d -a). Acute myocardial infarctions (heart attacks) that happen to young patients, especially those in their forties, can often be attributed to Antiphospholipid Syndrome (Nevras et al., 2023). There could be a few possible reasons as to why APS patients are more prone to ACS, such as plaque ruptures or an acute thrombosis event.

6. Valvular Heart Disease. This happens when any valve in the heart is damaged or diseased, with the most common being stenosis, where the valve becomes narrow or stiff, and thus unable to open fully to allow blood to flow through (CDC, 2024, May 31).

   Libman-Sacks endocarditis is present in 30% of APS patients, and according to Polytarchou et al. (2020):

   “Typically, patients with APS have valve thickening (>3 mm) of the proximal or middle portion of the leaflets, or irregular nodules on the atrial aspect of the edge of the mitral valve or the vascular surface of the edge of the aortic valve. The formation of valve vegetation, known as Libman-Sacks endocarditis, is the result of endocardial damage and thrombus formation.”

   I personally have had a mitral valve prolapse when I was 25, though I don’t think it can be solely attributed to APS as I have a whole assortment of chronic illnesses. I still remember slowly dying over the course of a year, as breathing became increasingly difficult. I managed to eventually get it repaired at Cleveland Clinic, as the local surgeons were not keen to touch a patient with Antiphospholipid Syndrome. That life-saving surgery was only made possible thanks to the hundreds of kind, generous souls who funded it.

7. Cardiomyopathy (heart muscle disorders). There are various types of conditions that can cause cardiomyopathy, which results in your heart being unable to pump blood efficiently. Over time, this weakens your heart and can lead to heart failure. APS patients, especially those with a comorbid SLE diagnosis, have an increased risk of cardiomyopathy, most likely due to “microvascular thrombosis, autoimmune vasculitis and myocarditis or microvascular fibrosis” (Polytarchou et al., 2020).
8. Intracardiac Thrombi. Cardiac thrombi can be commonly found in patients with ischaemic strokes, and it is important to distinguish them from other cardiac masses such as tumours, in order to render proper treatment (Alkindi et al., 2013). Intracardiac thrombosis is when a blood clot forms in the heart, which can also lead to pulmonary or peripheral embolisms.

This is not an exhaustive list of cardiological issues in relation to Antiphospholipid Syndrome, but I hope that it has granted you some insight into the mechanisms behind it, and that it serves to highlight the importance of maintaining good heart wherever possible (I personally could do better, for one…).

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Cutaneous Manifestations in Antiphospholipid Syndrome

Cutaneous (skin-related) manifestations are common and may actually be the first signs of Antiphospholipid Syndrome. In a study of 200 patients, Francès et al. (2005) found that 49% of APS or APS/SLE patients had dermatologic manifestations, and that it was the presenting manifestation in 30.5% of them. Kriseman et al. (2007) also notes that 40% of APS patients who have cutaneous manifestations go on to develop multisystemic thrombotic events, which underscores the need to be extra vigilant.

According to Gibson et al. (1997), cutaneous manifestations in Antiphospholipid Syndrome include:

“livedo reticularis, necrotizing vasculitis, livedoid vasculitis, thrombophlebitis, cutaneous ulceration and necrosis, erythematous macules, purpura, ecchymoses, painful skin nodules, and subungual splinter hemorrhages.”

Studies have shown that livedo reticularis is the most common dermatologic manifestation in APS patients, at about 55%. Another study of 70 patients with the lupus anticoagulant showed thrombophlebitis as the most common at about 34%. SLE is often associated with secondary cases, and chronic urticaria is also associated with autoimmune conditions in general, in approximately 50% of cases (Diógenes et al., 2004).

Let’s take a look at how Antiphospholipid Syndrome can affect the largest organ of the human body – the skin.

Livedo – The Most Common Dermatologic Manifestation in APS Patients

Livedo reticularis is a netlike, purplish discolouration of skin, thought to be caused through the constriction of blood vessels (Danan et al., 2021, January 19). This then disrupts blood flow, and results in oxygen-starved red blood cells accumulated beneath the skin. It may also be the presenting sign of APS, although it may be hard to tell as it can also occur in other individuals with or without other medical conditions.

There is also another form of livedo known as livedo racemosa, which presents as a discontinued network, and does not go away. It mostly occurs in the lower limbs, and for APS patients, usually happens due to organised thrombosis. Unlike livedo reticularis, livedo racemosa is commonly associated with thrombotic or inflammatory disorders (Pincelli et al., 2021).

Superficial Thrombophlebitis

Superficial thrombophlebitis is when there is inflammation of the veins just beneath your skin, and usually occurs in the legs. Symptoms include swelling, redness or tenderness, and sometimes a high fever (NHS, 2022, June 20). These are similar to that of a DVT, but with less severity. A small study of 45 patients with recurrent superficial thrombophlebitis also found a correlation with anticardiolipin antibodies (de Godoy et al., 2001).

Cutaneous Ulceration

According to Dobler et al. (2018), about 20% – 30% of Antiphospholipid Syndrome patients have lower extremity ulcers, which they posit might be due to “vascular endothelial damage at the microcirculation level, leading to intracapillary thrombosis and focal inflammation”.

Whilst the full pathology is yet to be fully understood, some recent studies have suggested that the antiphospholipid antibodies – lupus anticoagulant and anticardiolipin – might be risk factors for venous leg ulcers, which might cause repeated thrombosis that lead to chronic damage that are unable to heal properly over time (Takahashi et al., 2021).

Research I have found in relation to skin ulcers are mostly from case reports, where many of the ulcers resembled pyoderma gangrenosum, which is an ulcerative disorder that is not fully understood, but commonly linked with systemic diseases (Schmieder and Krishnamurthy, 2023, July 4). These ulcers either fully resolved with a combination of treatments including anticoagulation, although there was one case report of an ulcer that wasn’t able to heal for 7 years (Wei et al., 2022). In all of the case reports, the need for a multidisciplinary approach was emphasised.

You can learn more about anticoagulants and the various types of medications used in relation to APS in this post.

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Male & Female Reproductive Systems

I wrote a whole post about females and Antiphospholipid Syndrome which you can read about in the link below (and will follow up with one all about males at some point!). If you do not have the time, one thing to be aware of are ovarian cyst ruptures, which can come on suddenly, and is of life-threatening status. Having experienced it twice, I am now on birth control in a bid to prevent it from happening again.

Whether Antiphospholipid Syndrome contributes to infertility is still controversial, as there is insufficient data to conclude. However, there have been case reports of testicular thrombosis followed by orchiectomy (surgical procedure to remove testicle(s)) in males with APS, which could contribute to future infertility (El Hasbani et al., 2020).

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Musculoskeletal Manifestations in Antiphospholipid Syndrome

Several musculoskeletal manifestations have been reported in APS patients, namely: Arthralgia/Arthritis, Avascular Necrosis/Osteonecrosis, bone marrow necrosis, complex regional pain syndrome type-1 (reflex sympathetic dystrophy), muscle infarction, non-traumatic fractures and osteoporosis (Noureldine et al., 2016). Musculoskeletal manifestations can also be complicated by comorbidities, such as Lupus (SLE).

Patients on long-term warfarin therapy can also lose bone density as it is a Vitamin K antagonist, which is an important vitamin for bone health (Rodríguez-Olleros Rodríguez and Díaz Curiel, 2019). Learn more about Vitamin K antagonists here.

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Avascular Necrosis / Osteonecrosis

Avascular necrosis of bone (AVN) is also known as osteonecrosis (ON) or aseptic necrosis. It is a disease in which cell death occurs in components of bone, as a result of interruption in blood supply. AVN is associated with several autoimmune diseases.

For Antiphospholipid Syndrome, ischaemia is thought to be the main cause, with antiphospholipid antibodies associated with vessel thromboses. Thrombosis of terminal arteries in the subcondral areas (layers of bone just beneath the cartilage in a joint) has also been found in patients with non-traumatic AVN (Tektonidou and Moutsopoulos, 2006). Studies have shown that previous glucocorticoid (steroid) use and thrombocytopenia (low platelet count) may be contributing factors (Freire de Carvalho et al., 2021).

Osteopenia & Osteoporosis

Osteopenia refers to bone density loss, which can lead to osteoporosis where the bones have become weak and brittle, and thus can break easily (Cleveland Clinic, 2024b, March 19; Mayo Clinic, n.d. -a).

Long-term warfarin use has been associated with osteoporosis, especially for men. This might be due to its Vitamin K antagonistic effects, which interferes with bone formation (Gage et al., 2006). Another small study also showed a strong correlation between antiphospholipid antibodies and metatarsal fractures (which includes osteoporosis), although the role of warfarin is yet unclear (Sangle et al., 2004).

Learn more about warfarin here.

Arthralgia

As per Noureldine et al.’s (2016) review, Primary Antiphospholipid Syndrome (PAPS) is a common cause of arthralgia (pain in a joint). This is different from Arthritis, which is an actual diagnosis, and not a symptom (Hardin, 1990). Management of arthralgia and arthritis is primarily on a symptomatic basis, with drugs such as NSAIDs and analgesics.

According to Noureldine et al. (2016), osteoarticular pain might be due to a flare for SLE-APS patients, in which immunosuppressive agents and/or corticosteroids may be needed. I have both Sjögren’s and SLE, and based on my personal experience, only steroids work when I’m in an immense pain flare. Even strong painkillers do nothing to ease the pain.

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Neuropsychiatric Manifestations in Antiphospholipid Syndrome

Neuropsychiatry is a field of medicine which involves neurology and also mental illness (Royal College of Psychiatrists, n.d.). Antiphospholipid Syndrome is now recognised as a major neurological disease as well. Neurological events that can occur due to APS include: stroke, transient ischemic attacks (TIA), migraine, headaches, memory loss, ataxia (coordination/balance issues), symptoms that mimic Multiple Sclerosis, myelopathy, neuropathy, behavioural disorders and more (Hughes, 2003; Johns Hopkins Medicine, n.d. -a; Penn Medicine, n.d.; Healthdirect Australia, 2022, September).

The direct impact of antiphospholipid antibodies (aPLs) on the central nervous system (CNS) have also been postulated to explain the effect of neurological symptoms in APS patients. One study showed that aPLs bound to specific areas of the brain that impacted memory and learning functions. Another study associated long-term exposure to apLs with motor hypoactivity and impaired cognition, due to mature amyloid plaque deposition, and a relationship between thrombin and coagulation inhibitors. This could potentially increase the risk of Alzheimer’s Disease. The increased exposure to proinflammatory cytokines most likely play a role as well (Carecchio et al., 2014).

A lot of research still needs to be done in terms of APS and neuropsychiatric manifestations, as the mechanisms are yet to be fully understood. This is also a great video by Dr. Sanil Rege, who explains more about neuropsychiatric manifestations of APS in a simple manner (Psych Scene Hub, 2024, April 26), and another one on the subject by Prof. Graham Hughes (Psych Scene Hub, 2020, August 11).

Brain Fog / Cognitive Dysfunction

An impact in cognitive function is preferable to saying ‘brain fog’, which often makes the experience sound too trivial. Those who live with ‘brain fog’ know how devastating its impacts are. Cognitive dysfunction is also another annoying feature of APS involvement in the neurological pathways, and exists on a spectrum from mild to severe (such as dementia).

The frequency of cognitive dysfunction ranges from 19% to 40%, and includes cognitive complication with memory, executive function, visuospatial skills and visuomotor speed. APS patients can also present with psychiatric symptoms such as: psychosis, mania, depression, bipolar disorders, OCD and schizophrenia (Yelnik et al., 2016). Here is also a useful Q&A session with Dr. Yu, as he answers some questions from the APS community regarding brain fog (Yu, n.d.).

Combined with Lupus, Epilepsy, Sjögren’s disease, depression, anxiety and all the other medical conditions that I have, nailing down the culprit of my brain fog can be tricky. I often think that brain fog can be worse than pain, because at least there are coping strategies for pain to a certain extent. There is not much you can do for brain fog, where I have trouble adding 3 + 2, even. You can see how that’s detrimental to trying to get anything done, from simple chores to work.

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Stroke / Cerebrovascular Accident

A stroke is known medically as a cerebrovascular accident (State of Hawaii, Department of Health, n.d.), and is one of the big bad ones when Antiphospholipid Syndrome misbehaves. Apart from taking your medications fastidiously, steps for stroke prevention require modifications to your lifestyle. This includes eating a balanced diet (especially if you’re on warfarin), the avoidance of contact sports, and more. Basically, things you probably would not have thought about twice before your Antiphospholipid Syndrome diagnosis.

Studies have shown that triple positive APS patients are at the highest risk for thrombosis, whilst other studies have shown that patients with SLE with only lupus anticoagulant are at an equally high risk.

According to Mittal et al. (2023):

“Acute ischemic stroke (AIS) and transient ischemic attack (TIA) are the most common manifestations of arterial pathology in APS,⁷ with approximately 20% of patients with APS suffering a stroke more than 10 years.⁸ In individuals aged below 50 years, 17% of strokes and 12% of TIA are associated with aPL,⁹ suggesting APS is an important cause of strokes in younger patients.”

Another important thing to note is that more than 20% of strokes in patients younger than 45 years of age may be attributed to Antiphospholipid Syndrome (Ricarte et al., 2018). It is also more common in males.

Transient Ischaemic Attack (TIA)

A transient ischaemic attack (TIA) is a ‘mild stroke’ event that doesn’t last for long, and occurs when blood supply to the brain is cut off briefly. Symptoms include: numbness especially on one side of the body, confusion, vision problems, dizziness, and loss of coordination in articulation and balance (National Institute of Neurological Disorders and Stroke, n.d.). I also know a friend with Lupus (SLE) in her mid-30s, who was recently diagnosed with APS, as she had suffered a stroke with atypical symptoms.

Strokes and transient ischaemic attacks (TIAs) are the most common neuropsychiatric manifestations of Antiphospholipid Syndrome. A TIA was actually my first manifestation and experience with APS at 14, where exactly half of my body was numb. It was a strange sensation, almost as if I were sliced into half with precision. I brushed it off as a heat stroke, as I had just endured a physical training session under the hot sun. I was still joking with my friend as we dragged my body to a general practitioner, who referred me to a neurologist. I then received an Antiphospholipid Syndrome diagnosis, and I can still remember that devastating day with clarity, even 20 years on.

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Ophthalmologic / Ocular Manifestations in Antiphospholipid Syndrome

Ophthalmology is a field in medicine with many sub-specialties, and deals with the eyes and vision, their functions and diseases (Churchill and Gudgel, 2024, February 24). It is important to note that thrombosis can occur in the eyes as well. Apart from antiphospholipid antibodies (aPLs), proinflammatory cytokines also play a role in triggering thrombosis.

As usual, comorbidities such as SLE can worsen things; according to Neto et al. (2023), up to 1/4 of APS/SLE and SLE patients had retinal abnormalities, and the presence of aPL triple positivity and a high aGAPSS score also seem to be risk factors for paracentral acute middle maculopathy (a type of ischemic maculopathy) (Mishra et al., 2023).

There are a number of ocular and neuroophthalmic manifestations that have been found in APS patients, including but not limited to: retinal arteritis, retinal venous occlusion, ischemic optic neuropathy, transient loss of vision and diplopia (Suvajac et al., 2007). Both anterior and posterior eye segments can be affected (Franco et al., 2020), and sometimes symptoms overlap with neurological-type manifestations such as headache and migraine-like visual symptoms (Uludag et al., 2021).

According to Suvajac et al. (2007), the most frequent ocular manifestation in APS is retinal thrombosis, especially in young adults. In secondary APS, occlusion of central retinal artery and vein (OACR, OVCR) is the most common finding. Patients with Lupus (SLE) on top of Antiphospholipid Syndrome have a compounding of ophthalmic issues, such as scleritis, extraocular thromboses, and optic neuropathy. Catastrophic APS (CAPS) is rare but can also affect the eyes, which can even lead to permanent vision loss (Morel et al., 2021).

Ocular and ophthalmic manifestations in Antiphospholipid Syndrome was previously thought to be rare, but further studies have revealed that they actually occur in 15 – 88% of patients (Suvajac et al., 2007). Interestingly, risk factors associated with retinal vasculopathy include APS-related kidney and heart valve disease, as well as obstetric morbidity (Xie et al., 2022).

Retinal Venous Occlusion

Retinal vein occlusion (RVO) is a multifactorial retinal vascular disease that can cause vision damage and blindness, and is common amongst the elderly. Antiphospholipid antibodies are also a risk factor for RVO, especially in patients less than 45 years of age (Zhu et al., 2015). In a study by Hernández et al. (2020), it was found that 10% of the patients with RVO had antiphospholipid antibodies, and that up to 90% of their RVO-APS patients had at least one vascular risk factor.

Pulmonary Manifestations in Antiphospholipid Syndrome

Pulmonary thromboembolisms and pulmonary hypertension are the most common manifestations of APS in the lungs. Sometimes, patients get a pulmonary embolism first, which leads to a diagnosis of Antiphospholipid Syndrome.

Other APS and lung issues include, but are not limited to: microvascular pulmonary thrombosis, pulmonary capillaritis, alveolar haemorrhage, acute respiratory distress syndrome (ARDS) and postpartum syndrome (Espinosa et al., 2002).

Pulmonary Embolism (PE)

A Pulmonary Embolism (PE) is when a blood clot develops in one of your veins (often in the legs), and travels to lodge itself in a lung artery, blocking blood flow (Johns Hopkins Medicine, n.d. -c). There is a high mortality rate for PEs, with Antiphospholipid Syndrome as a risk factor. According to Shi et al.( 2022) in a study of 76 patients with PE:

“The risk factors for APS in PE patients are male, low PLT, prolonged APTT and slightly increased D-dimer.”

Many people who live with all types of chronic illnesses or disabilities tend to “wait for a bit and see”. Going to the A&E is not fun – I don’t think I need to explain why. It is also uncomfortable, full of other sick people, and all that waiting around makes you even more dehydrated and exhausted. “Is it worth a trip? The pain isn’t so bad…yet…right?”, you think to yourself. And I’ve had that thought many times.

But if you have breathlessness or any persistent chest pains that will not go away, especially where painkillers don’t even help – then please just go to the A&E. A pulmonary embolism can be deadly, and the longer you wait, the more damage it will cause.

You can read about my personal experience with Pulmonary Embolism in this post. This medical incident put my body under huge physical and mental stress, which subsequently activated all the other genes for Lupus, Sjögren’s and more, which might have otherwise remained dormant.

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Vascular Manifestations in Antiphospholipid Syndrome

The vascular system is also known as the circulatory system. It consists of the blood vessels (arteries and veins), capillaries (tiny arteries between blood vessels), and lymph vessels. Its functions include blood circulation and lymphatic drainage. These have overlaps with the respiratory, digestive, kidney and urinary system, as well as temperature control, as they all rely on the vascular system (Johns Hopkins Medicine, n.d. -b). This also means that vascular manifestations of Antiphospholipid Syndrome can happen within any of these pathways.

There is increasing evidence that activation of the mammalian target of rapamycin complex (mTORC) pathway by antiphospholipid antibodies (aPLs) is associated with vascular lesions (Canaud et al., 2014). In a study of 48 APS patients, it was also found that those with increased TLR-2 and TLR-4 (toll-like receptor proteins) had endothelial dysfunction, arterial stiffening, and hypertrophy (Benhamou et al., 2014).

No matter the organ involved, most of these vascular manifestations occur as acute or chronic lesions and/or thrombosis in various forms. These can subsequently lead to more specific medical issues, such as stenotic/occlusive coronary arterial disease in the heart, “APS nephropathy” in the kidneys, on top of a myriad of other vascular-related diseases. It is also important to note, once again, that comorbidities such as Lupus (SLE) compounds these issues, due to a wide variety of added factors (Siddique et al., 2017).

Diffuse Alveolar Haemorrhage

Diffuse Alveolar Haemorrhage (DAH) is a small vessel vasculitis that damages the lung microvasculature, so the most fatal complication often involves the respiratory system (Stoots et al., 2019). This is a rare condition that can happen to APS patients, with a high mortality rate between 30.3% – 45.8%.

Symptoms of diffuse alveolar haemorrhage include: dyspnea (shortness of breath), cough, hypoxemia (low blood oxygen levels), hemoptysis (coughing blood out from the lungs), fever, and more. Treatment is usually fairly aggressive, and include: glucocorticoids, immunosuppressive therapy, plasma exchange, and more. More than half of APS patients with DAH are estimated to have a relapse within 5 years of follow-up (Figueroa-Parra et al., 2023).

Conclusion: How Does Antiphospholipid Syndrome Affect the Body?

As you can see, Antiphospholipid Syndrome is a systemic autoimmune disease that goes beyond its status as a ‘mere’ blood disorder. Blood is life, and blood clots can occur in any part of your body, leading to potentially detrimental effects. Thus, it is critical to take your APS diagnosis seriously. Learn from my mistakes – sticking to a regular balanced diet and avoiding contact sports are some things you can do to help lessen the risk of a severe incident. You may not be experiencing pain in the present moment, but remember that prevention is better than cure.

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Read Related Posts in the Antiphospholipid Syndrome Diagnosis Series:
• Antiphospholipid Syndrome Diagnosis: The A to Z Guide as a Patient
• Latest Research on Antiphospholipid Syndrome (2024 Edition)
• Pregnancy, Miscarriage & Women’s Health in Antiphospholipid Syndrome
• The Lowdown on Medications & Antiphospholipid Syndrome (Warfarin, Enoxaparin, DOACs, NSAIDs & More)
• The Annoying Thing About Living with Antiphospholipid Syndrome (My Personal Experiences)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• What it Feels Like to be Refused Treatment by a Hospital’s A&E / ER

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References:
1. Alkindi, F., Hamada, A. H. S., & Hajar, R. (2013). Cardiac Thrombi in Different Clinical Scenarios. Heart Views : The Official Journal of the Gulf Heart Association, 14(3), 101–105. https://doi.org/10.4103/1995-705X.125924
2. Artim-Esen, B., Diz-Küçükkaya, R., & İnanç, M. (2015). The Significance and Management of Thrombocytopenia in Antiphospholipid Syndrome. Current Rheumatology Reports, 17(3), 14. https://doi.org/10.1007/s11926-014-0494-8
3. Biggioggero, M., & Meroni, P. L. (2010). The geoepidemiology of the antiphospholipid antibody syndrome. Autoimmunity Reviews, 9(5), A299–A304. https://doi.org/10.1016/j.autrev.2009.11.013
4. Carecchio, M., Cantello, R., & Comi, C. (2014). Revisiting the Molecular Mechanism of Neurological Manifestations in Antiphospholipid Syndrome: Beyond Vascular Damage. Journal of Immunology Research, 2014(1), 239398. https://doi.org/10.1155/2014/239398
5. CDC. (2024, May 31). About Valvular Heart Disease. CDC. Retrieved from: https://www.cdc.gov/heart-disease/about/valvular-heart-disease.html
6. Chen, H. H., Lin, C. H., & Chao, W. C. (2021). Risk of systemic lupus erythematosus in patients with anti-phospholipid syndrome: a population-based study. Frontiers in medicine, 8, 654791. https://doi.org/10.3389/fmed.2021.654791
7. Churchill, J., & Gudgel, D. T. (2024, February 24). What Is an Ophthalmologist vs Optometrist? American Academy of Ophthalmology. Retrieved from: https://www.aao.org/eye-health/tips-prevention/what-is-ophthalmologist
8. Cleveland Clinic. (2022a, May 2). Acute Coronary Syndrome. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/22910-acute-coronary-syndrome
9. Cleveland Clinic. (2022b, May 12). Endothelial Dysfunction. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/23230-endothelial-dysfunction
10. Cleveland Clinic. (2022c, June 19). Veins. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/body/23360-veins
11. Cleveland Clinic. (2022d, August 4). Hyperlipidemia. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/21656-hyperlipidemia
12. Cleveland Clinic. (2022e, August 19). Antiphospholipid Syndrome. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/21685-antiphospholipid-syndrome
13. Cleveland Clinic. (2024a, February 15). Atherosclerosis. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/16753-atherosclerosis-arterial-disease
14. Cleveland Clinic. (2024b, March 19). Osteopenia. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/21855-osteopenia
15. Cleveland Clinic. (2024c, May 24). Unstable Angina. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/21744-unstable-angina
16. Danan, V., Harp, J., & Erkan, D. (2021, January 19). Antiphospholipid Syndrome and Skin Problems – Top 10 Series. Hospital for Special Surgery. Retrieved from: https://www.hss.edu/conditions_top-ten-antiphospholipid-syndrome-skin-problems.asp
17. Dobler, C., Szeyko, L. A., Landeros, M. M., Arango, C. P., Noble, L. S., Tano, S. V., & Herrada, J. (2018). Resolution of Intractable Leg Ulcers Associated with Antiphospholipid Syndrome (APS) with Prophylactic Dose of Aspirin (ASA) and Enoxaparin: A Case Report. Blood, 132, 5071. https://doi.org/10.1182/blood-2018-99-110752
18. El Hasbani, G., Khamashta, M., & Uthman, I. (2020). Antiphospholipid syndrome and infertility. Lupus, 29(2), 105–117. https://doi.org/10.1177/0961203319893763
19. Espinosa, G., Cervera, R., Font, J., & Asherson, R. A. (2002). The lung in the antiphospholipid syndrome. Annals of the Rheumatic Diseases, 61(3), 195–198. https://doi.org/10.1136/ard.61.3.195
20. Figueroa-Parra, G., Meade-Aguilar, J. A., Langenfeld, H. E., González-Treviño, M., Hocaoglu, M., Hanson, A. C., Prokop, L. J., Murad, M. H., Cartin-Ceba, R., Specks, U., Majithia, V., Crowson, C. S., & Duarte-García, A. (2023). Clinical features, risk factors, and outcomes of diffuse alveolar hemorrhage in antiphospholipid syndrome: A mixed-method approach combining a multicenter cohort with a systematic literature review. Clinical Immunology, 256, 109775. https://doi.org/10.1016/j.clim.2023.109775
21. Forastiero, R. (2012). Bleeding in the antiphospholipid syndrome. Hematology, 17(sup1), s153–s155. https://doi.org/10.1179/102453312X13336169156654
22. Francès, C., Niang, S., Laffitte, E., Pelletier, F. le, Costedoat, N., & Piette, J. C. (2005). Dermatologic manifestations of the antiphospholipid syndrome: Two hundred consecutive cases. Arthritis & Rheumatism, 52(6), 1785–1793. https://doi.org/10.1002/art.21041
23. Franco, A. M. de M., Medina, F. M. C., Balbi, G. G. M., Levy, R. A., & Signorelli, F. (2020). Ophthalmologic manifestations in primary antiphospholipid syndrome patients: A cross-sectional analysis of a primary antiphospholipid syndrome cohort (APS-Rio) and systematic review of the literature. Lupus, 29(12), 1528–1543. https://doi.org/10.1177/0961203320949667
24. Freire de Carvalho, J., Correia de Araujo, R. P., & Skare, T. L. (2021). Osteonecrosis in Primary Antiphospholipid Syndrome is Associated with Previous Glucocorticoid Use and Thrombocytopenia. Rheumatology and Therapy, 8(3), 1255–1261. https://doi.org/10.1007/s40744-021-00333-9
25. Gage, B. F., Birman-Deych, E., Radford, M. J., Nilasena, D. S., & Binder, E. F. (2006). Risk of Osteoporotic Fracture in Elderly Patients Taking Warfarin: Results From the National Registry of Atrial Fibrillation 2. Archives of Internal Medicine, 166(2), 241–246. https://doi.org/10.1001/archinte.166.2.241
26. García-Carrasco, M., Pinto, C. M., Hernández, C. J., Poblano, J. C. S., Morales, I. E., & Martínez, S. M. (2013). Antiphospholipid syndrome. In Autoimmunity: From Bench to Bedside [Internet]. El Rosario University Press. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK459442/
27. Gibson, G. E., Daniel Su, W. P., & Pittelkow, M. R. (1997). Antiphospholipid syndrome and the skin. Journal of the American Academy of Dermatology, 36(6), 970–982. https://doi.org/10.1016/S0190-9622(97)80283-6
28. Hardin, J. G. (1990). Arthralgia. In H. K. Walker, W. D. Hall, & J. W. Hurst (Eds.), Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.). Butterworths. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK303/
29. Healthdirect Australia. (2022, September). Neuropathy. Healthdirect Australia. Retrieved from: https://www.healthdirect.gov.au/neuropathy
30. Hernández, J. L., Sanlés, I., Pérez-Montes, R., Martínez-Taboada, V. M., Olmos, J. M., Salmón, Z., Sierra, I., Escalante, E., & Napal, J. J. (2020). Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion. Thrombosis Research, 190, 63–68. https://doi.org/10.1016/j.thromres.2020.04.005
31. Huang, C., Ding, Y., Chen, Z., Wu, L., Wei, W., Zhao, C., Yang, M., Lin, S., Wang, Q., Tian, X., Zhao, J., Li, M., & Zeng, X. (2025). Future atherosclerotic cardiovascular disease in systemic lupus erythematosus based on CSTAR (XXVIII): The effect of different antiphospholipid antibodies isotypes. BMC Medicine, 23(1), 8. https://doi.org/10.1186/s12916-024-03843-9
32. Hughes, G. R. V. (2003). Migraine, memory loss, and “multiple sclerosis ”. Neurological features of the antiphospholipid (Hughes’) syndrome. Postgraduate Medical Journal, 79(928), 81–83. https://doi.org/10.1136/pmj.79.928.81
33. Johns Hopkins Medicine. (n.d. -a). Ataxia. Johns Hopkins Medicine. Retrieved 2024, July 1, from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/ataxia
34. Johns Hopkins Medicine. (n.d. -b). Overview of the Vascular System. Johns Hopkins Medicine. Retrieved 2024, July 1, from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/overview-of-the-vascular-system
35. Johns Hopkins Medicine. (n.d. -c). Pulmonary Embolism. Johns Hopkins Medicine. Retrieved 2024, July 1, from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/pulmonary-embolism
36. Kriseman, Y. L., Nash, J. W., & Hsu, S. (2007). Criteria for the diagnosis of antiphospholipid syndrome in patients presenting with dermatologic symptoms. Journal of the American Academy of Dermatology, 57(1), 112–115. https://doi.org/10.1016/j.jaad.2006.11.033
37. Mayo Clinic. (n.d. -a). Osteoporosis. Mayo Clinic. Retrieved 2024, July 1, from: https://www.mayoclinic.org/diseases-conditions/osteoporosis/symptoms-causes/syc-20351968
38. Mayo Clinic. (n.d. -b). Stroke. Mayo Clinic. Retrieved 2024, July 1, from: https://www.mayoclinic.org/diseases-conditions/stroke/symptoms-causes/syc-20350113
39. MedLine Plus. (n.d.). Fibrinolysis – primary or secondary. National Library of Medicine. Retrieved 2024, July 1, from https://medlineplus.gov/ency/article/000577.htm
40. Mishra, P., Mohanty, S., Shanmugasundaram, P., Moharana, B., & Das, D. (2023). Paracentral Acute Middle Maculopathy As the Presenting Sign of Ischemic Cardiomyopathy. Cureus, 15(2). https://doi.org/10.7759/cureus.35418
41. Mittal, P., Quattrocchi, G., Tohidi-Esfahani, I., Sayar, Z., Chandratheva, A., & Cohen, H. (2023). Antiphospholipid syndrome, antiphospholipid antibodies, and stroke. International Journal of Stroke, 18(4), 383–391. https://doi.org/10.1177/17474930221150349
42. Morel, N., Bonnet, C., Mehawej, H., Le Guern, V., Pérard, L., Roumier, M., Brezin, A., Godeau, B., Haroche, J., Benhamou, Y., Lambert, M., Yelnik, C. M., Maillard, N., Bodaghi, B., Piette, J.-C., & Costedoat-Chalumeau, N. (2021). Catastrophic Antiphospholipid Syndrome And Posterior Ocular Involvement: Case Series of 11 Patients and Literature Review. Retina, 41(11), 2332. https://doi.org/10.1097/IAE.0000000000003185
43. National Heart, Lung, and Blood Institute. (2023, May 1). Pulmonary Hypertension – What Is Pulmonary Hypertension? National Institutes of Health. Retrieved from: https://www.nhlbi.nih.gov/health/pulmonary-hypertension
44. National Heart, Lung, and Blood Institute. (2022, March 24). Platelet Disorders — Thrombocytopenia. National Institutes of Health. Retrieved from: https://www.nhlbi.nih.gov/health/thrombocytopenia
45. National Institute of Neurological Disorders and Stroke. (n.d.). Transient Ischemic Attack (TIA). National Institutes of Health. Retrieved 2024, July 1, from:https://www.ninds.nih.gov/health-information/disorders/transient-ischemic-attack-tia
46. Neto, E. D. S., Neto, T. S. R., Signorelli, F., Balbi, G. G. M., Higashi, A. H., Monteiro, M. L. R., Bonfá, E., Andrade, D. C. O., & Zacharias, L. C. (2023). Ocular retinal findings in asymptomatic patients with antiphospholipid syndrome secondary to systemic lupus erythematosus. Clinical Rheumatology, 42(8), 2105–2114. https://doi.org/10.1007/s10067-023-06613-9
47. Nevras, V., Milaras, N., Katsioulis, C., Sotiriou, Z., Tsalamandris, S., Gkounti, G., & Skevos, S. (2023). Acute Coronary Syndromes in Antiphospholipid Syndrome-above Suspicion: A Systematic Review. Current Problems in Cardiology, 48(3), 101503. https://doi.org/10.1016/j.cpcardiol.2022.101503
48. NHS. (2022, June 20). Symptoms – Antiphospholipid syndrome (APS). NHS. Retrieved from: https://www.nhs.uk/conditions/antiphospholipid-syndrome/symptoms/
49. Noureldine, M. H. A., Khamashta, M. A., Merashli, M., Sabbouh, T., Hughes, G. R. V., & Uthman, I. (2016). Musculoskeletal manifestations of the antiphospholipid syndrome. Lupus, 25(5), 451–462. https://doi.org/10.1177/0961203316636467
50. Orlando Health. (n.d.). Warning Signs of Pulmonary Hypertension and How To Treat It. Orlando Health. Retrieved 2024, July 1, from: https://www.orlandohealth.com/content-hub/warning-signs-of-pulmonary-hypertension-and-how-to-treat-it
51. Penn Medicine. (n.d.). Myelopathy. Penn Medicine. Retrieved 2024, July 1, from: https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/myelopathy
52. de Godoy, J. M. P., Batigalia, F., & Braile, D. M. (2001). Superficial thrombophlebitis and anticardiolipin antibodies: report of association. Angiology, 52(2), 127. https://doi.org/10.1177/000331970105200206
53. Polytarchou, K., Varvarousis, D., & Manolis, A. S. (2020). Cardiovascular Disease in Antiphospholipid Syndrome. Current Vascular Pharmacology, 18(6), 538–548. https://doi.org/10.2174/1570161117666190830101341
54. Przysinda, A., Feng, W., & Li, G. (2020). Diversity of Organism-Wide and Organ-Specific Endothelial Cells. Current Cardiology Reports, 22(4), 19. https://doi.org/10.1007/s11886-020-1275-9
55. Psych Scene Hub. (2024, April 26). Antiphospholipid Syndrome and the Brain (Neuropsychiatric Manifestations of APS) — Dr Sanil Rege. Psych Scene Hub. Retrieved from: https://psychscenehub.com/video/antiphospholipid-syndrome-aps-in-psychiatry-neuropsychiatric-manifestations-dr-sanil-rege/
56. Psych Scene Hub. (2020, August 11). Neuropsychiatric Manifestations in Antiphospholipid Syndrome (APS) — Prof Graham Hughes. Psych Scene Hub. Retrieved from: https://psychscenehub.com/video/neuropsychiatric-manifestations-in-aps-by-prof-graham-hughes/
57. Reyes, N., & Abe, K. (2023, May 1). Deep Vein Thrombosis & Pulmonary Embolism | CDC Yellow Book 2024. CDC. Retrieved from: https://wwwnc.cdc.gov/travel/yellowbook/2024/air-land-sea/deep-vein-thrombosis-and-pulmonary-embolism
58. Ricarte, I. F., Dutra, L. A., Abrantes, F. F., Toso, F. F., Barsottini, O. G. P., Silva, G. S., de Souza, A. W. S., & Andrade, D. (2018). Neurologic manifestations of antiphospholipid syndrome. Lupus, 27(9), 1404–1414. https://doi.org/10.1177/0961203318776110
59. Rodríguez-Olleros Rodríguez, C., & Díaz Curiel, M. (2019). Vitamin K and Bone Health: A Review on the Effects of Vitamin K Deficiency and Supplementation and the Effect of Non-Vitamin K Antagonist Oral Anticoagulants on Different Bone Parameters. Journal of Osteoporosis, 2019, 2069176. https://doi.org/10.1155/2019/2069176
60. Royal College of Psychiatrists. (n.d.). Neuropsychiatrist. Royal College of Psychiatrists. Retrieved 2024, July 1, from: https://www.rcpsych.ac.uk/become-a-psychiatrist/choose-psychiatry/what-is-psychiatry/types-of-psychiatrist/neuropsychiatry
61. Sangle, S., D’Cruz, D. P., Khamashta, M. A., & Hughes, G. R. V. (2004). Antiphospholipid antibodies, systemic lupus erythematosus, and non-traumatic metatarsal fractures. Annals of the Rheumatic Diseases, 63(10), 1241–1243. https://doi.org/10.1136/ard.2003.016105
62. Schmieder, S. J., & Krishnamurthy, K. (2023, July 4). Pyoderma Gangrenosum. In StatPearls. StatPearls Publishing. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK482223/
63. Shi, M., Gao, W., Jin, Y., Zhu, J., Liu, Y., Wang, T., & Li, C. (2022). Antiphospholipid Syndrome-Related Pulmonary Embolism: Clinical Characteristics and Early Recognition. Frontiers in Cardiovascular Medicine, 9, 872523. https://doi.org/10.3389/fcvm.2022.872523
64. Stanford Health Care. (n.d -a). Non-obstructive Coronary Artery Disease. Stanford Health Care. Retrieved 2024, July 1, from: https://stanfordhealthcare.org/medical-conditions/blood-heart-circulation/non-obstructive-coronary-artery-disease.html
65. Stanford Health Care. (n.d -b). Endothelial Dysfunction. Stanford Health Care. Retrieved 2024, July 1, from: https://stanfordhealthcare.org/medical-conditions/blood-heart-circulation/endothelial-dysfunction.html
66. State of Hawaii, Department of Health. (n.d.). Stroke Medical Terminology. State of Hawaii, Department of Health. Retrieved 2024, July 1, from: https://health.hawaii.gov/nt/stroke/stroke-medical-terminology/
67. Suvajac, G., Stojanovich, L., & Milenkovich, S. (2007). Ocular manifestations in antiphospholipid syndrome. Autoimmunity Reviews, 6(6), 409–414. https://doi.org/10.1016/j.autrev.2006.11.005
68. Takahashi, K., Ikeda, T., Yokoyama, K., & Kawakami, T. (2021). Cutaneous ulcer resembling pyoderma gangrenosum in a patient with antiphospholipid syndrome. Journal of Cutaneous Immunology & Allergy, 4(1). https://doi.org/10.1002/cia2.12143
69. Tektonidou, M. G. (2022). Cardiovascular disease risk in antiphospholipid syndrome: Thrombo-inflammation and atherothrombosis. Journal of Autoimmunity, 128, 102813. https://doi.org/10.1016/j.jaut.2022.102813
70. Tektonidou, M. G., & Moutsopoulos, H. M. (2006). Osteoarticular Manifestations of Antiphospholipid Syndrome. In M. A. Khamashta (Ed.), Hughes Syndrome: Antiphospholipid Syndrome (pp. 127–139). Springer. https://doi.org/10.1007/1-84628-009-5_12
71. Uludag, G., Onghanseng, N., Tran, A. N. T., Hassan, M., Halim, M. S., Sepah, Y. J., Do, D. V., & Nguyen, Q. D. (2021). Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations. Journal of Ophthalmic Inflammation and Infection, 11(1), 11. https://doi.org/10.1186/s12348-021-00240-8
72. Velásquez, M., Rojas, M., Abrahams, V. M., Escudero, C., & Cadavid, Á. P. (2018). Mechanisms of Endothelial Dysfunction in Antiphospholipid Syndrome: Association With Clinical Manifestations. Frontiers in Physiology, 9, 1840. https://doi.org/10.3389/fphys.2018.01840
73. Ward, T. (2024, April 5). What do long flights do to our bodies? National Geographic. Retrieved from: https://www.nationalgeographic.com/premium/article/long-flights-dehydration-pain-nausea-dvt
74. Wei, M., Xu, Y., Xia, D., Li, J., & Dong, S. (2022). Care and Treatment for an Antiphospholipid Syndrome-Related Lower Limb Skin Ulcer Unhealed for 7 Years: A Case Report. The International Journal of Lower Extremity Wounds, 15347346221090079. https://doi.org/10.1177/15347346221090079
75. World Health Organization. (2023, March 16). Hypertension. World Health Organization. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/hypertension
76. World Health Organization. (n.d.). Cardiovascular diseases. World Health Organization. Retrieved 2024, July 1, from: https://www.who.int/health-topics/cardiovascular-diseases
77. Wu, K. K., & Thiagarajan, P. (1996). Role of endothelium in thrombosis and hemostasis. Annual Review of Medicine, 47, 315–331. https://doi.org/10.1146/annurev.med.47.1.315
78. Xie, Z., Li, H., Qi, W., Li, J., Wu, C., Hu, C., Jiang, N., Wang, Q., Tian, X., Li, M., Zhao, J., Sui, R., & Zeng, X. (2022). Characteristics and risk factors of retinal vasculopathy in antiphospholipid syndrome. Lupus, 31(2), 178–186. https://doi.org/10.1177/09612033211069762
79. Yelnik, C. M., Kozora, E., & Appenzeller, S. (2016). Non-stroke Central Neurologic Manifestations in Antiphospholipid Syndrome. Current Rheumatology Reports, 18(2), 11. https://doi.org/10.1007/s11926-016-0568-x
80. Yu, R. Z. (n.d.). What Is APS “Brain Fog”? What Are Some Strategies to Help Manage It? Michigan Medicine. Retrieved 2024, July 1, from: https://medicine.umich.edu/dept/intmed/what-aps-%E2%80%9Cbrain-fog%E2%80%9D-what-are-some-strategies-help-manage-it
81. Zhu, W., Wu, Y., Xu, M., Wang, J. Y., Meng, Y. F., Gu, Z., & Lu, J. (2015). Antiphospholipid antibody and risk of retinal vein occlusion: a systematic review and meta-analysis. Plos one, 10(4), e0122814. https://doi.org/10.1371/journal.pone.0122814

If there are specific terms or topics in this post that you were wondering about, such as injections, diet, bone health or something else, you can probably find in answers in the find the answers in the complete Antiphospholipid Syndrome A – Z guide here!

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*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

A Brief Introduction to Vitamin K

Vitamin K is important to know all about as a patient with Antiphospholipid Syndrome, as it interacts with warfarin and is a key contributor to the blood clotting process. It is a fat-soluble vitamin that comes in the form of vitamin K1 (phylloquinone) and vitamin K2 (a series of menaquinones). There is also a synthetic form – Vitamin K3 (menadione), which is no longer used in dietary supplements as they have been found to damage hepatic cells (Office of Dietary Supplements, 29 March, 2021).

Vitamin K1 is the main form of vitamin K in the human diet, and can mostly be found in green, leafy vegetables, certain fruits, and its absorption is increased in the presence of butter or oils. Vitamin K2 is mainly derived from fermented foods, dairy produce and animal-based sources.

According to Halder et al. (2019):

“VKDPs [vitamin K-dependent proteins] are categorized as hepatic and extra-hepatic VKDPs. Hepatic VKDPs include coagulation factors II, VII, IX, X, and anticoagulant protein C, protein S, and protein Z, all of which are involved in regulating blood coagulation. Extra-hepatic VKDPs include Matrix Gla protein (MGP), Osteocalcin, and Gla-rich protein (GRP). These VKDPs are primarily involved in maintaining bone homeostasis, as well as inhibiting ectopic calcification.”

In basic terms, what this means is that vitamin K, whether in K1 or K2 form, is an essential component of blood clotting processes, maintenance of bone health, and prevention of vessel mineralisation, depending on how and where they are metabolised. Whilst it’s important to be aware of vitamin K, I won’t deep dive into it in this post as I’d like to focus on medications and Antiphospholipid Syndrome.

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Vitamin K Antagonists (VKAs)

Vitamin K antagonists (VKAs) are a class of medications used for the treatment and prevention of thrombosis. The most well-known and commonly used VKA is warfarin. For the sake of interest, other types of VKAs include: ethyl biscoumacetate, phenindione, anisindione, dicoumarol, phenprocoumon and diphenadione. There is a reason why warfarin is the most commonly used, as many of these other VKAs are erratic, highly toxic, or can cause other adverse side effects (Vardanyan and Hruby, 2006).

The administration of VKAs is convenient and practical, as they can be taken orally, and have a long half-life (warfarin has a half-life of 36 – 42 hours). Doctors are also able to adjust dosages for more precision in individual patients as needed, based on risk factors and medical history. VKAs work by antagonising the enzyme vitamin K epoxide reductase (VKOR) to prevent vitamin K from being recycled. This results in inhibition of the coagulation cascade, as many clotting factors rely on vitamin K to synthesise (Schein et al., 2016).

Coumarins

Vitamin K antagonists such as warfarin, acenocoumarol and phenprocoumon are derivatives of coumarin, which can be of natural or synthetic origin. In 1945, Karl Link experimented with 150 naturally occurring coumarin derivatives, before concluding that one compound was particularly active – warfarin. For a rare subset of patients with mutations in VKOR, VKAs are unfortunately low in efficacy or ineffective due to coumarin resistance (Kasperkiewicz et al., 2020). Read more about coumarins in the A to Z APS resource guide here.

Warfarin – THE Medication for Antiphospholipid Syndrome

Warfarin is a vitamin K antagonist, and is probably the most important drug for the management of Antiphospholipid Syndrome, and for the prevention of thrombosis. There are two brands of warfarin available – Coumadin and Marevan. It is important to stick to the same brand, as the formulation is not an exact match. What that means is that the anticoagulation effects can vary between each brand, and might mess your INR up. Do discuss with your doctor first, should you need to switch brands for any reason.

(Not so) fun fact: Warfarin also first started out as rat poison, but has declined in usage for such purposes due to an increase in resistance from these rodents, which is inheritable (Thijssen, 1995).

How Warfarin Works to Prevent Blood Clotting

Warfarin inhibits vitamin K dependent clotting factors II, VII, IX, and X, and also the anticoagulant proteins C and S (Crader et al., 1 May, 2023). This means that it inhibits multiple pathways in the blood clotting process, as compared to DOACs, which only disrupt a specific point. Specifically, prothrombin, FVII, FIX, protein C, and protein S are strictly related to blood coagulation processes (Girolami et al., 2018). Approximately 10% – 40% of factors II, VII, IX and X are inhibited by warfarin (Wadelius et al., 2004).

Vitamin K ‘activates’ these clotting factors via the enzyme, epoxide reductase, which is inhibited by warfarin. In rare cases, patients who are first taking warfarin may experience warfarin-induced skin necrosis. This is especially true for patients who are deficient in protein C, as it has the shortest half-life amongst them all. In such cases, patients are often co-administered heparin, as it has a quicker effect (Barmore et al., 24 February, 2023).

How Warfarin is Metabolised

Warfarin is a potent anticoagulant that is well absorbed by the body via the intestine with 90% bioavailability, and also offers high water solubility. It is then metabolised in the liver (hepatic), primarily through the CYP2C9 enzyme, with a half-life of approximately 20 – 60 hours. Other minor enzymatic pathways for metabolism include: CYP2C8, 2C18, 2C19, 1A2, and 3A4. How much of the drug gets metabolised is also dependent on each individual’s genetic variations (Patel et al., 24 March, 2023; Kasperkiewicz et al., 2020).

The warfarin molecule is further broken down into two forms – S- and R-warfarin, with S-warfarin 3 – 5 times more potent than R-warfarin. They are mainly broken down in the liver; metabolism of active S-warfarin is mainly via the CYP2C9 enzyme, and CYP enzymes CYP1A2 and CYP3A for R-warfarin.

Does Warfarin Interact with Other Medications?

The issue with warfarin is that it is also highly bound to serum albumin, which when combined with cytochrome P450 (CYP) metabolism, interacts with many drugs and foods. This results in warfarin either becoming more or less potent – thus increasing or decreasing its anticoagulatory effects, which can be risky either way for a patient with Antiphospholipid Syndrome (Tay et al., 2013).

Some drugs that interact with the CYP450 2C9 are cardiovascular medications such as amiodarone, and anti-infectives such as fluconazole. Some drugs that interact with CYP1A2 or CYP3A4 are quinolones and macrolides (bactericidal antibiotics). Inhibition of these enzymes can enhance the effects of warfarin, thus increasing the risk for bleeding further. Other drugs such as rifampicin (an antibiotic), carbamazepine (an anticonvulsant) and azathioprine (a DMARD) on the other hand, induces these enzymes and can decrease the potency of warfarin (Tay et al., 2013).

Highly Probable to Highly Improbable Interactions

In a systematic review by Holbrook et al. (2005), they categorise drugs that might potentially interact with warfarin from level 1 (highly probable) to level 4 (highly improbable). According to Holbrook et al. (2005):

“Of all 184 reviewed reports, 128 (70%) described a potentiation of warfarin’s effect, while inhibition and “no effect” reports each comprised 28 (15%). There were 34 reports of a major interaction—3 case reports of thrombosis associated with trazodone, sulfasalazine, and propofol and 31 case reports describing a major potentiation.”

Some drugs also yielded conflicting evidence for interaction with warfarin, i.e. terbinafine, ritonavir, and influenza vaccine. Linkins (2013) breaks down these medication categories by Holbrook et al. (2005) into a table according to type – antibiotics, antifungals, cardiovascular, cholesterol lowering agents, analgesics or antiinflammatory agents, and others. This is definitely not an exhaustive list of medications that interact with warfarin – there are way too many to be listed in one post, plus many others whose interactions are yet unknown.

What if I Have No Choice but to Take a Medication That Interacts with Warfarin?

Sometimes, taking medications that interact with warfarin is unavoidable, such as antibiotics for an infection, or an essential drug for another medical condition. For example, I was on carbamazepine and azathioprine for a period of time in the past, in a bid to control my epilepsy and Lupus (SLE) activity.

First, your rheumatologist (or doctor who manages your warfarin and Antiphospholipid Syndrome) should be consulted. They will then monitor and adjust your warfarin dose as needed, in combination with the other medications. As the medications I took were on a daily basis, that makes things easier as the main strategy to maintaining your target INR range is consistency in medication and food intake.

I eventually had to stop taking those medications not because they interacted with warfarin, but because they were ineffective or unsuitable for me for various reasons. Your doctor will also work with you to retitrate your warfarin dose when and if you need to stop taking these other medications. Remember that this applies to major dietary changes as well.

The main takeaway that I’d like to highlight is to always inform and work with your doctor when introducing a new medication that might potentially interfere with warfarin. Another important point is to always state that you’re on warfarin when you visit any new healthcare professional, including (especially) at the A&E/ER. In fact, you should have received a medical card that states that you are on warfarin – laminate this and keep it with you at all times so that you can show it to them.

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How to Check for Warfarin Interaction with Other Medications

Often, it can be a hassle and impractical to consult your doctor every time you need to take a new medication or food product. I personally use the MedScape app on my phone to do a quick check for medication interactions on the fly (I’ve seen doctors use it as well!). It tells you if there are minor or major contraindications, and why. It’s especially handy when I’m travelling. You can also tap into its comprehensive database to learn more about any other medication.

They also have a browser version here that you can use, plus other educational tools and resources on their website. Do note that it’s still important to cross-check with other verified sources and your doctor whenever possible, as not everything may be 100% accurate – that is impossible as research can sometimes be conflicting, and is also being constantly updated with new discoveries. (You can check out the latest research on Antiphospholipid Syndrome in this post.)

Screenshot Examples of the MedScape App:

How Much Warfarin Do I Need to Take with Antiphospholipid Syndrome?

The dose requirement of warfarin varies more than 10-fold amongst patients, due to genetic polymorphisms of CYP2C9, dietary differences, and other factors. According to Takahashi and Echizen (2003):

“Therapeutic targets measured by international normalized ratio (INR) of prothrombin time appear to differ between populations: INR of 2–3 for most indications in Caucasian patients¹ and 1.5–2.5 for Asian patients.”

And according to Wadelius et al. (2004):

“CYP2C9 variants, age, weight, concurrent drug treatment and indication for treatment significantly influenced warfarin dosing in these patients, explaining 29% of the variation in dose. CYP3A5 did not affect warfarin dosing.”

Thus, there is no hard and fast rule as to how much warfarin one should take, as that needs to be titrated on an individual basis. Apart from the diverse genetic and dietary differences amongst patients, other factors need to be taken into account as well, such as comorbidities and the medications used to treat them, medical history, and other risk factors. If you’ve had had a thrombosis in the past, your INR target range might need to be higher as well, as that is an indication of an increased risk for blood clotting.

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Tecarfarin – A Novel Vitamin K Antagonist in Phase III Trials

Tecarfarin is a novel VKA with a structural analog of warfarin, and can be measured via INR just like warfarin. It is being developed by Cardrenal Therapeutics for patients with implanted medical devices, end-stage renal disease (ESRD) and atrial fibrillation (AFib), although they are looking to expand its scope to include other patients who require anticoagulation too, such as in APS.

It has orphan drug with fast track designation from the FDA – meaning to say that it has governmental support for its development as a pharmaceutical agent for rare diseases. It is currently in Phase III clinical trials and in fact, since the time I drafted this section, it has already completed the ARIES-HM3 trial and presented its findings at the International Society for Heart & Lung Transplantation (ISHLT) 44th Annual Meeting & Scientific Sessions on June 3, 2024.

There are over hundreds of medications and foods that warfarin can interact with, due to the way it is metabolised by CYP2C9. Genetic variability in CYP2C9 gene can also affect the instability of INR. Tecarfarin on the other hand is metabolised by hCE-2, a pathway with no significant drug interactions, or genetic variability (Albrecht et al., 2017). It however, does not display any advantages over warfarin for people with VKORC1 polymorphisms.

In a multicentre study of 66 AFib patients for up to 12 weeks in a phase IIA trial, tecarfarin was shown to be well-tolerated without any adverse effects (Ellis et al., 2009). It was also shown to be well-tolerated in a small study of 40 healthy Chinese volunteers in a phase I trial (Zhou et al., 2023).

This means that tecarfarin might be a potential warfarin alternative or even replacement in future, as research has shown thus far similar effects as warfarin, minus the many interactions with other foods and drugs. I guess only time will tell, after it jumps through all the hoops of the essential clinical trials! (You can check out the latest research in this post.)

Enoxaparin – Another Important Medication in the APS Treatment Arsenal

We’ve covered quite a bit on warfarin, because it is so important when it comes to medications and Antiphospholipid Syndrome. Another important drug is enoxaparin (brand names: Lovenox and Clexane), which is also known as a “low molecular weight heparin” (LMWH). Two other FDA approved LMWHs in the USA are dalteparin (Fragmin) and tinzaparin (Innohep). Note that they should not be used interchangeably.

Enoxaparin is a medication that’s commonly substituted for warfarin, when APS patients need to pause their warfarin intake for whatever reason. It is often used as a bridge medication between surgical operations, where there is a higher chance of excessive bleeding.

This does not only include major surgeries, but also minor ones such as dental procedures, implantation of contraceptive devices, and procedures that require intramuscular injections such as the HPV vaccine. Enoxaparin has a quicker onset as compared to warfarin, and only has a half-life of about 4.5 – 7 hours (Cook, 2010). Hence, it is safer to be on enoxaparin during periods where excessive bleeding might be anticipated. You will need to do a warfarin reversal when switching to enoxaparin, which your doctor and gynaecologist will guide you through.

Whilst derived from heparin, the final formulation of enoxaparin is different. It has a bioavailability of 90% when given in the subcutaneous form (injection into the fat just under the skin), and is a more stable and predictable drug that can be self-administered by patients at home (Jupalli and Iqbal, 28 August, 2023). Pregnant women with APS generally need to substitute warfarin for enoxaparin/LMWH during the term of their pregnancy, as warfarin can be harmful to foetuses. You can read more about pregnancy with Antiphospholipid Syndrome here.

How Does Enoxaparin / LMWH Work?

According to Lawrence (2011):

“[LMWHs and fondaparinux] target anti–factor Xa activity rather than AT [antithrombin]. With LMWH and fondaparinux, there is a reduced risk of heparin-induced thrombocytopenia (HIT), and monitoring of the aPTT is also not required, because the aPTT is insensitive to alterations in factor Xa.”

This means that the anticoagulatory mechanisms of LMWH differs from that of vitamin K antagonists, and that patients do not need to measure their INR like they do when on warfarin. I actually prefer being on enoxaparin as compared to warfarin despite the hassle of injections, because it gives me a chance to indulge in all the foods I love (yes, like broccoli and tofu…), as it does not interact with foods in the same way as VKAs do. Sadly, enoxaparin is not a good long-term medication as it is known to impair bone health and bone healing (Li et al., 2022). You can learn more about musculoskeletal manifestations in APS here.

Having said that, that does not mean that there are no drug interactions with enoxaparin. Mayo Clinic has listed some medications that can interact with enoxaparin here, and also certain medical conditions that should be highlighted to your doctor if you have them.

Differences Between ‘Standard’ Heparin and Low Molecular Weight Heparin

It is easy to get confused between enoxaparin/LMWH and heparin, since technically enoxaparin is derived from heparin. Many patients and sometimes even doctors refer to enoxaparin as heparin in casual speech. However, whilst enoxaparin can be self-administered by the patient via subcutaneous injections, unfractionated heparin (UFH) is usually given intravenously within a hospital setting, as there is a risk of Heparin Induced Thrombocytopenia (HIT).

HIT is a life-threatening condition where massive activation of platelets take place, with multi-cellular release of micro particles that contribute to hypercoagulability (Gruel et al., 2020). Compared to LMWH, unfractionated heparin is a highly variable drug as well, where almost 75% of patients fail to achieve the intended aPTT. Hence, patients need to be closely monitored when on unfractionated heparin (Krishnaswamy et al., 2010).

According to Krishnaswamy et al. (2010):

“Unfractionated heparin (UFH) exerts its effect by binding and inducing a conformational change in antithrombin (AT), converting AT to a more efficient inhibitor of circulating thrombin (factor IIa), factor Xa, factor IXa, factor XIIa, and kallikrein. Contributing to its efficiency, heparin can dissociate from the thrombin: AT complex and catalyze the activity of other AT molecules.”

Referring back to Lawrence’s (2011) explanation of the mechanisms of LMWHs, in comparison unfractionated heparin readily binds to antithrombin as well. This makes unfractionated heparin a more potent anticoagulant as compared to LMWH – but also brings with it more complications and bleeding risks. It is still an important medication to combat acute cases and medical emergencies however, such as pulmonary embolisms and heart attacks.

Learn more about pulmonary and cardiovascular manifestations in APS, and also more about thrombocytopenia in this post.

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DOACs & Antiphospholipid Syndrome

DOACs stands for ‘Direct Oral Anticoagulants’, and they can be categorised into these main classifications: oral direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban, and betrixaban), and direct thrombin inhibitors (i.e. dabigatran) (Nasiri et al., 2022).

You can actually skip this entire section with a main takeaway – warfarin is still the mainstay drug for patients with Antiphospholipid Syndrome, especially for those who are high risk, or who have had a thrombosis before. However knowing me, I went down the research rabbit hole and found a lot of interesting information about these anticoagulants. I’ve actually asked my own rheumatologist before why I can’t be on DOACs as opposed to warfarin, as their benefits seemed much better. Now I know clearly why. If you’re interested to learn how DOACs work as an anticoagulant and why they aren’t quite recommended for APS patients, then read on!

What are DOACs and How do They Work?

DOACs are anticoagulants like VKAs, but their mechanism differs. The main advantages are that patients who are on DOACs need not monitor their diet or INR, and they have a rapid onset and offset of action (Pastori et al., 2021). One interesting finding about DOACs is that beyond their anticoagulation properties, they may also have an anti-inflammatory, anti-fibrotic and anti-angiogenic properties (Signorelli et al., 2018).

That might sound great, but APS patients are advised to use VKAs such as warfarin instead, especially if you’ve had a history of arterial thrombosis, or are triple positive, or even maybe double positive for antiphospholipid antibodies (Girón-Ortega and Girón-González, 2023; also see Bejjani et al., 2024). I personally have had multiple DVTs and a PE before, so my target INR with warfarin needs to be higher than the average APS patient, as I am at a greater risk of clotting. That can be better achieved via VKAs as compared to DOACs.

VKAs also target all phases of thrombin generation, whereas DOACs target only the initiation and/or propagation process. Rivaroxaban and apixaban in particular were found to be significantly inferior to VKAs for the prevention of recurrent thrombosis in APS patients (Girón-Ortega and Girón-González, 2023). DOACs also showed an increased risk of stroke amongst APS patients, and they may also be at a higher risk of thrombotic events (Shah et al., 2023).

Another problem with DOACs is that not all of them have an antidote at present, and more studies are yet to be done as to their safety and efficacy in actual patients. There are also specific groups of individuals whom DOACs are not suitable for, such as those with poor renal function, who have a prosthetic heart valve, a disorder of haemostasis, amongst others (Tran et al., 2014).

What is Thrombin?

A blood clot is also known as a thrombus, and thrombin plays an important role in the blood clotting process. Thrombin converts fibrinogen to fibrin, which is a tough protein that forms blood clots to seal wound sites. Thrombin is also the most potent platelet agonist (i.e. clots the blood). The more technical explanation, according to Posma et al. (2019):

“Activation of the blood coagulation cascade leads to fibrin deposition and platelet activation that are required for hemostasis. However, aberrant activation of coagulation can lead to thrombosis. Thrombi can cause tissue ischemia, and fibrin degradation products and activated platelets can enhance inflammation.”

DOACs: Direct Thrombin Inhibitors (DTIs)

According to Eriksson et al. (2011):

“DTIs directly neutralize thrombin by occupying the catalytic binding site, fibrinogen binding site, or both. DTIs also inhibit both fluid-phase and fibrin-bound thrombin.”

They do pretty much what their name states – inhibition of thrombin, which results in a reduction of blood clotting. A key advantage of DTIs is their ability to bind directly to thrombin, and they do not bind to other plasma proteins either (Lee and Ansell, 2011).

Dabigatran – The Only Approved DTI

The only approved DTI for use at present is dabigatran etexilate, which is a prodrug that metabolises into dabigatran in the body. Other DTIs such as ximelagatran have been withdrawn due to hepatotoxicity reports (Posma et al., 2019; van Ryn et al., 2013). Dabigatran is approved in over 70 countries, for the purpose of stroke prevention in patients with atrial fibrillation, and for the prevention of thrombosis after orthopaedic hip and knee surgery (van Ryn et al., 2013).

Whilst dabigatran seems to be a highly effective anticoagulant with a good safety profile thus far, it is important to note that it is primarily used in patients who don’t have Antiphospholipid Syndrome. International guidelines still indicate VKAs as the choice drug for patients with APS, especially if they have experienced a blood clotting event before, or are a high-risk patient, such as being triple positive (Pastori et al., 2021).

DOACs: Factor Xa Inhibitors

Factor Xa inhibitors on the other hand, reduces thrombin generation, and thus interferes with the process of fibrinogen to fibrin conversion. They also have no direct effect on platelet aggregation. It is theorised that this targeted action on factor Xa serves to limit the cascade of thrombin generation, and therefore less of the drug may be needed as compared to a DTI. Factor Xa also has minimal functions outside of coagulation, unlike thrombin, and side effects may be more contained (Cabral and Ansell, 2015).

Apixaban (Eliquis) – A Highly Selective Factor Xa Inhibitor

Apixaban (brand name: Eliquis) is a DOAC originally approved for atrial fibrillation (Afib) patients to reduce the risk of strokes and blood clots. It was later approved to treat DVTs and PEs (pulmonary embolisms) as well. It is a highly selective factor Xa inhibitor that exerts no effect on platelet aggregation, and mainly binds to plasma protein (Agrawal et al., 22 February, 2024). Side effects of taking apixaban are similar to other anticoagulant drugs, and include: bleeding, red or black, tarry stools, red, pink or brown urine, trouble breathing, dizziness, coughing up blood or material that looks like coffee grounds, and more.

Rivaroxaban (Xarelto) – Another Factor Xa Inhibitor

Rivaroxaban (brand name: Xarelto) is another type of DOAC under the factor Xa class. Based on the data available to date, rivaroxaban is less effective than VKAs in the prevention of recurrent thrombosis, but more research needs to be done as to its efficacy (Girón-Ortega and Girón-González, 2023).

A study of 120 high risk APS patients was terminated early due to the higher incidence of thromboembolic events for those who were on rivaroxaban, whereas none occurred in the group on warfarin (Pengo et al., 2018).

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Current Reversal Agents Available for Anticoagulant Drugs

Patients who are on anticoagulants ironically run the risk of excessive bleeding or a haemorrhage, and not all DOACs have an antidote; the antidotes that are available are also expensive. In cases of severe bleeding, patients need to undergo reversal of their anticoagulant medication via a haemostatic agent.

According to Tomaselli et al. (2020) and Kustos and Fasinu (2019), these are the current reversal agents used for anticoagulant drugs during emergencies:

1. Vitamin K Antagonists (warfarin) – Intravenous or oral vitamin K1. In addition, prothrombin complex concentrate (PCC) is preferred for immediate reversal, as compared to fresh frozen plasma (FFP) (Tran et al., 2013). Compared to FFP, 4F-PCCs contain approximately 25 times the concentration of vitamin K-dependent factors, and thus can be given at a smaller volume with a faster infusion rate.
2. Vitamin K Antagonists (heparin) – Protamine.
3. Indirect Thrombin Inhibitors (LMWH) – Protamine.
4. DTI (dabigatran) – Idarucizumab (Praxbind). If unavailable, PCC or aPCC (activated prothrombin complex concentrate).
5. Factor Xa Inhibitors (apixaban & rivaroxaban) – Andexanet Alfa. If unavailable, PCC or aPCC.
6. Factor Xa (betrixaban & edoxaban) – Off-label treatment with high dose Andexanet Alfa. If unavailable, PCC or aPCC.
7. In addition for the DOACs, activated charcoal may be considered for known recent ingestion in the last 2 – 4 hours.

This is just a brief, general guideline, and many more considerations need to be taken into account on an individual basis during an emergency. Please work with your own doctors and emergency care team for the best outcome.

A Bit More About Andexanet Alfa as a Reversal Agent

Andexanet alfa is administered via intravenous infusion with an onset time of 2 minutes. Side effects are primarily hot flashes and antibody development; they may also induce blood clotting ironically and result in strokes, DVTs, PEs, cardiac failure and more (Kustos and Fasinu, 2019; also see Escal et al., 2024). It is currently only approved for use as an antidote for apixaban and rivaroxaban, whilst its safety and efficacy is still being evaluated in relation to edoxaban and betrixaban.

Learn more about how APS affects major organs such as the lungs, brain and heart in this post.

Ciraparantag & Other Non-Specific Pharmacokinetic Antidotes to DOACs

Ciraparantag is a reversal agent still undergoing clinical trials, but shows promise as a non-immunogenic antidote for a wide array of anticoagulants (all types of DOACs, heparins and fondaparinux) (Escal et al., 2024).

Non-specific pharmacokinetic antidotes are sometimes used in addition to reversal agents to increase coagulation effects. According to Escal et al. (2024), these include:

• Activated Charcoal – Activated charcoal has the ability to absorb various substances in the body within the gastrointestinal tract. It may help to reduce blood concentrations of DOACs and thus its bioavailability. It also remains active for a long time and is low in cost.
• Haemodialysis – This is more for patients on DTIs (dabigatran), and especially if they have renal impairment. They are ineffective for Factor Xa inhibitors as they mainly bind to plasma proteins. It can be difficult to access during emergency situations however, as it requires trained healthcare professionals who know how to use specific equipment.
• Haemostatic Agents – These are useful when the type of DOAC the patient is on is unknown, or when standard reversal agents are unavailable. They include naPCC (non-activated prothrombin complex concentrates), FEIBA (factor eight inhibitor bypassing activity), rFVIIa (recombinant activated factor VII) and tranexamic acid. Note that these are second-line treatments and that more research still needs to be done to determine their exact effects and safety profile.

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Proteases & Protease-Activated Receptor (PAR) Antagonists

Proteases are important regulators of cellular activity, and they communicate directly to cells via protease-activated receptors (PARs). There are four different PAR profiles, from PAR1 to PAR4, which are expressed widely in the body, from the brain to lungs, muscles, bones, bladder and more (Han et al., 2021). PAR1, PAR3 and PAR4 are activated by thrombin, whereas Factor Xa activates PAR2, although other proteases can also contribute to activation (Posma et al., 2019).

Cleavage of PARs

Inflammation is at the tail end of the blood coagulation cascade, as can be seen from a graphic in this paper by Posma et al. (2019).

According to Burzynski et al. (2019):

“The current principal link between coagulation and immunity is cleavage of PARs by thrombin, which produces cytokines and inflammation.”

This reveals a direct link between coagulation and the immune system, which is an exciting perspective. What this means is that future Antiphospholipid Syndrome treatments might shift to an immunological one, instead of merely targeting anticoagulation. Unfortunately, despite the implication of PARs in Antiphospholipid Syndrome, there are no ongoing trials for APS patients (Signorelli et al., 2018). Let’s keep our fingers crossed! (Read this post for the latest research on APS.)

Vorapaxar – An FDA-Approved PAR Antagonist

Vorapaxar is a first-in-class PAR1 antagonist approved for use by the FDA, for patients with coronary artery disease. Unfortunately, it is contraindicated for patients who have had thrombotic or bleeding events in the past. Like all antiplatelet agents, vorapaxar increases the risk of bleeding, which can be fatal. It also has a long half-life and no antidote (Han et al., 2021; Signorelli et al., 2018).

Another PAR-1 antagonist is atopaxar, but research has been discontinued as clinical trials in phase II demonstrated a high risk for bleeding with the drug (Zhao et al., 2013).

NSAIDs & Antiphospholipid Syndrome

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are a class of anti-inflammatories that people often take for generic pain relief. You’re probably familiar with these over-the-counter drugs that go by the names of: Ibuprofen, Naproxen and Aspirin. Brand names include Neurofen, Advil, Motrin, Aleve, Alka-Seltzer, Pepto-Bismol, and more.

To be honest, NSAIDS would probably work better for my Lupus and Sjögren’s pains because of their anti-inflammatory properties, but I can’t take them due to interactions with warfarin. As I’m also allergic to paracetamol (Panadol), I can only rely on opioid classes of painkillers for pain relief.

NSAIDs interfere with blood clotting by inhibiting platelet function. Platelets (also known as thrombocytes) are essential components in our blood that help with clotting. Hence, patients who are on blood thinning medications have a higher risk of bleeding with NSAIDs.

There is also an increased risk of gastrointestinal bleeding and peptic ulcers with NSAIDs due to the mechanisms of the medication (Drini, 2017), which is also the biggest concern my rheumatologist has with them. I only use NSAIDs when absolutely necessary, such as during a high fever, and inform my healthcare team when I do so. I also take extra measures to protect my stomach such as eating proper meals, and check my own INR regularly.

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• What’s it Like to be on a High Dose of Steroids? (And the First Question You Will Definitely Ask)
• Drink Pure Wine Review (A Product That Excites Me as a Person with Chronic Illness)
• 12 Visible Evidence of a Body Gone Rogue (Is Invisible Illness Truly Invisible?)

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Conclusion to Medications and Antiphospholipid Syndrome

In this post, we have covered medications and Antiphospholipid Syndrome, as well as some of the important drugs that can interact with warfarin, and new medications that are undergoing clinical trials.

I hope that this post on medications and Antiphospholipid Syndrome has been insightful and useful to you whether as an APS patient, or someone who is caring for one. Should you have any questions, experiences to share, or corrections (I am not a doctor, after all!), feel free to leave a comment below. Don’t forget to check out the rest of the posts in the Antiphospholipid Syndrome series listed below as well. Wishing you all the best that life can still bring!

P.s. If you’d like to support the work I do, you can keep me fueled with coffee using the button below. You can also sign up for our mailing list so you don’t miss out on our latest posts. You will receive an e-book full of uplifting messages, quotes and illustrations, as a token of appreciation!

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Read Related Posts in the Antiphospholipid Syndrome Diagnosis Series:
• Antiphospholipid Syndrome Diagnosis: The A to Z Guide as a Patient
• Latest Research on Antiphospholipid Syndrome (2024 Edition)
• Pregnancy, Miscarriage & Women’s Health in Antiphospholipid Syndrome
• How Does Antiphospholipid Syndrome Affect The Body? (Beyond the Blood to Major Organs)
• The Annoying Thing About Living with Antiphospholipid Syndrome (My Personal Experiences)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• http://What it Feels Like to be Refused Treatment by a Hospital’s A&E / ER

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References:

1. Agrawal, A., Kerndt, C. C., & Manna, B. (22 February, 2024). Apixaban. In StatPearls. StatPearls Publishing. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK507910/
2. Albrecht, D., Ellis, D., Canafax, D. M., Combs, D., Druzgala, P., Milner, P. G., & Midei, M. G. (2017). Pharmacokinetics and pharmacodynamics of tecarfarin, a novel vitamin K antagonist oral anticoagulant. Thrombosis and Haemostasis, 117(04), 706-717. https://doi.org/10.1160/TH16-08-0623
3. Barmore, W., Bajwa, T., & Burns, B. (24 February, 2023). Biochemistry, Clotting Factors. In StatPearls. StatPearls Publishing. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK507850/
4. Bejjani, A., Khairani, C. D., Assi, A., Piazza, G., Sadeghipour, P., Talasaz, A. H., Fanikos, J., Connors, J. M., Siegal, D. M., Barnes, G. D., Martin, K. A., Angiolillo, D. J., Kleindorfer, D., Monreal, M., Jimenez, D., Middeldorp, S., Elkind, M. S. V., Ruff, C. T., Goldhaber, S. Z., … Bikdeli, B. (2024). When Direct Oral Anticoagulants Should Not Be Standard Treatment. Journal of the American College of Cardiology, 83(3), 444–465. https://doi.org/10.1016/j.jacc.2023.10.038
5. Burzynski, L. C., Humphry, M., Pyrillou, K., Wiggins, K. A., Chan, J. N. E., Figg, N., Kitt, L. L., Summers, C., Tatham, K. C., Martin, P. B., Bennett, M. R., & Clarke, M. C. H. (2019). The Coagulation and Immune Systems Are Directly Linked through the Activation of Interleukin-1α by Thrombin. Immunity, 50(4), 1033-1042.e6. https://doi.org/10.1016/j.immuni.2019.03.003
6. Cabral, K. P., & Ansell, J. E. (2015). The role of factor Xa inhibitors in venous thromboembolism treatment. Vascular Health and Risk Management, 11, 117–123. https://doi.org/10.2147/VHRM.S39726
7. Cadrenal Therapeutics, Inc. (3 June, 2024). Cadrenal Therapeutics Highlights Presentation Of New Trial Data at Ishlt Conference Demonstrating The Importance Of Anticoagulation Quality In LVAD Patients. Cadrenal Therapeutics, Inc. Retrieved from: https://www.cadrenal.com/investors/press-releases/detail/cadrenal-therapeutics-provides-third-quarter-2023-corporate-update
8. Cadrenal Therapeutics, Inc. (9 November, 2023). Cadrenal Therapeutics Provides Third Quarter 2023 Corporate Update. U.S. Securities And Exchange Commission. Retrieved from: https://www.sec.gov/Archives/edgar/data/1937993/000121390023084969/ea187953ex99-1_cadrenal.htm
9. Cadrenal Therapeutics, Inc. (n.d.). Tecarfarin. A late-stage novel therapy with orphan drug and Fast Track designations. Cadrenal Therapeutics, Inc. Retrieved from: https://www.cadrenal.com/tecarfarin/
10. Cleveland Clinic. (28 April, 2022). Platelets. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/body/22879-platelets
11. Cook, B. W. (2010). Anticoagulation Management. Seminars in Interventional Radiology, 27(4), 360–367. https://doi.org/10.1055/s-0030-1267849
12. Crader, M. F., Johns, T., & Arnold, J. K. (1 May, 2023). Warfarin Drug Interactions. In StatPearls. StatPearls Publishing. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK441964/
13. Department of Health, Government of Western Australia. (n.d.). Warfarin. HealthyWA. Retrieved from: https://www.healthywa.gov.au/Articles/A-Z/Warfarin
14. Drini, M. (2017). Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Australian Prescriber, 40(3), 91–93. https://doi.org/10.18773/austprescr.2017.037
15. Drugs .com. (n.d.). Enoxaparin (Ingredient). Drugs .com. Retrieved from: https://www.drugs.com/ingredient/enoxaparin.html
16. Ellis, D. J., Usman, M. H., Milner, P. G., Canafax, D. M., & Ezekowitz, M. D. (2009). The First Evaluation of a Novel Vitamin K Antagonist, Tecarfarin (ATI-5923), in Patients With Atrial Fibrillation. Circulation, 120(12), 1029–1035. https://doi.org/10.1161/CIRCULATIONAHA.109.856120
17. Eriksson, B. I., Quinlan, D. J., & Eikelboom, J. W. (2011). Novel Oral Factor Xa and Thrombin Inhibitors in the Management of Thromboembolism. Annual Review of Medicine, 62(Volume 62, 2011), 41–57. https://doi.org/10.1146/annurev-med-062209-095159
18. Escal, J., Lanoiselée, J., Poenou, G., Zufferey, P., Laporte, S., Mismetti, P., & Delavenne, X. (2024). Latest advances in the reversal strategies for direct oral anticoagulants. Fundamental & Clinical Pharmacology. https://doi.org/10.1111/fcp.12992
19. Girolami, A., Ferrari, S., Cosi, E., Santarossa, C., & Randi, M. L. (2018). Vitamin K-Dependent Coagulation Factors That May be Responsible for Both Bleeding and Thrombosis (FII, FVII, and FIX). Clinical and Applied Thrombosis/Hemostasis, 24(9 Suppl), 42S-47S. https://doi.org/10.1177/1076029618811109
20. Girón-Ortega, J. A., & Girón-González, J. A. (2023). Direct-acting oral anticoagulants in antiphospholipid syndrome: A systematic review. Medicina Clínica (English Edition), 161(2), 65–77. https://doi.org/10.1016/j.medcle.2023.03.017
21. Gruel, Y., De Maistre, E., Pouplard, C., Mullier, F., Susen, S., Roullet, S., Blais, N., Le Gal, G., Vincentelli, A., Lasne, D., Lecompte, T., Albaladejo, P., Godier, A., Albaladejo, P., Belisle, S., Blais, N., Bonhomme, F., Borel-Derlon, A., Borg, J. Y., … Zufferey, P. (2020). Diagnosis and management of heparin-induced thrombocytopenia. Anaesthesia Critical Care & Pain Medicine, 39(2), 291–310. https://doi.org/10.1016/j.accpm.2020.03.012
22. Halder, M., Petsophonsakul, P., Akbulut, A. C., Pavlic, A., Bohan, F., Anderson, E., Maresz, K., Kramann, R., & Schurgers, L. (2019). Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. International Journal of Molecular Sciences, 20(4), Article 4. https://doi.org/10.3390/ijms20040896
23. Han, X., Nieman, M. T., & Kerlin, B. A. (2020). Protease‐activated receptors: An illustrated review. Research and Practice in Thrombosis and Haemostasis, 5(1), 17–26. https://doi.org/10.1002/rth2.12454
24. Harvard Medical School. (16 December, 2019). Bad mix: Blood thinners and NSAIDs. Harvard Health Publishing. Retrieved from: https://www.health.harvard.edu/diseases-and-conditions/bad-mix-blood-thinners-and-nsaids
25. Holbrook, A. M., Pereira, J. A., Labiris, R., McDonald, H., Douketis, J. D., Crowther, M., & Wells, P. S. (2005). Systematic Overview of Warfarin and Its Drug and Food Interactions. Archives of Internal Medicine, 165(10), 1095–1106. https://doi.org/10.1001/archinte.165.10.1095
26. Jupalli, A., & Iqbal, A. M. (28 August, 2023). Enoxaparin. In StatPearls. StatPearls Publishing. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK539865/
27. Kasperkiewicz, K., Ponczek, M. B., Owczarek, J., Guga, P., & Budzisz, E. (2020). Antagonists of Vitamin K—Popular Coumarin Drugs and New Synthetic and Natural Coumarin Derivatives. Molecules, 25(6), 1465. https://doi.org/10.3390/molecules25061465
28. Krishnaswamy, A., Lincoff, A. M., & Cannon, C. P. (2010). The Use and Limitations of Unfractionated Heparin. Critical Pathways in Cardiology, 9(1), 35. https://doi.org/10.1097/HPC.0b013e3181d29713
29. Kustos, S. A., & Fasinu, P. S. (2019). Direct-Acting Oral Anticoagulants and Their Reversal Agents-An Update. Medicines (Basel, Switzerland), 6(4), 103. https://doi.org/10.3390/medicines6040103
30. Lawrence, P. F. (2011). Chapter 78—Pharmacologic Adjuncts to Endovascular Procedures. In W. S. Moore & S. S. Ahn (Eds.), Endovascular Surgery (Fourth Edition) (pp. 807–813). W.B. Saunders. https://doi.org/10.1016/B978-1-4160-6208-0.10078-3
31. Lee, C. J., & Ansell, J. E. (2011). Direct thrombin inhibitors. British Journal of Clinical Pharmacology, 72(4), 581–592. https://doi.org/10.1111/j.1365-2125.2011.03916.x
32. Li, Y., Liu, L., Li, S., Sun, H., Zhang, Y., Duan, Z., & Wang, D. (2022). Impaired bone healing by enoxaparin via inhibiting the differentiation of bone marrow mesenchymal stem cells towards osteoblasts. Journal of Bone and Mineral Metabolism, 40(1), 9–19. https://doi.org/10.1007/s00774-021-01268-5
33. Mayo Clinic. (1 February, 2024). Enoxaparin (Intravenous Route, Subcutaneous Route, Injection Route). Mayo Clinic. Retrieved from: https://www.mayoclinic.org/drugs-supplements/enoxaparin-intravenous-route-subcutaneous-route-injection-route/side-effects/drg-20063670?p=1
34. MedlinePlus. (15 April, 2023). Rivaroxaban. Bethesda (MD): National Library of Medicine (US). Retrieved from: https://medlineplus.gov/druginfo/meds/a611049.html
35. MedlinePlus. (15 November, 2023). Apixaban. Bethesda (MD): National Library of Medicine (US). Retrieved from: https://medlineplus.gov/druginfo/meds/a613032.html
36. Nasiri, A., AlQahtani, A., Rayes, N. H., AlQahtani, R., Alkharras, R., & Alghethber, H. (2022). Direct oral anticoagulant: Review article. Journal of Family Medicine and Primary Care, 11(8), 4180–4183. https://doi.org/10.4103/jfmpc.jfmpc_2253_21
37. Office of Dietary Supplements. (29 March, 2021). Vitamin K Fact Sheet for Health Professionals. National Institutes of Health. Retrieved from: https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/
38. Pastori, D., Menichelli, D., Cammisotto, V., & Pignatelli, P. (2021). Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines. Frontiers in Cardiovascular Medicine, 8. https://doi.org/10.3389/fcvm.2021.715878
39. Pengo, V., Denas, G., Zoppellaro, G., Jose, S. P., Hoxha, A., Ruffatti, A., Andreoli, L., Tincani, A., Cenci, C., Prisco, D., Fierro, T., Gresele, P., Cafolla, A., De Micheli, V., Ghirarduzzi, A., Tosetto, A., Falanga, A., Martinelli, I., Testa, S., … Banzato, A. (2018). Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood, 132(13), 1365–1371. https://doi.org/10.1182/blood-2018-04-848333
40. Patel, S., Singh, R., Preuss, C. V., & Patel, N. (24 March, 2023). Warfarin. In StatPearls. StatPearls Publishing. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK470313/
41. Posma, J. J., Grover, S. P., Hisada, Y., Owens, A. P., Antoniak, S., Spronk, H. M., & Mackman, N. (2019). Roles of Coagulation Proteases and PARs (Protease-Activated Receptors) in Mouse Models of Inflammatory Diseases. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(1), 13–24. https://doi.org/10.1161/ATVBAHA.118.311655
42. Ruff, C. T. (17 May, 2022). Direct Oral Anticoagulants (DOACs) vs. Warfarin: Key Differences. North American Thrombosis Forum [NATF]. Retrieved from: https://thrombosis.org/2020/11/doacs-vs-warfarin/
43. Schein, J. R., White, C. M., Nelson, W. W., Kluger, J., Mearns, E. S., & Coleman, C. I. (2016). Vitamin K antagonist use: Evidence of the difficulty of achieving and maintaining target INR range and subsequent consequences. Thrombosis Journal, 14(1), 14. https://doi.org/10.1186/s12959-016-0088-y
44. Shah, B. B., Shankar, A., Kumar, V., Kumar, S., Malik, U. A., Majeed, A., … & Ahmed, S. (2023). Direct oral anticoagulants vs. vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis. Annals of Medicine and Surgery, 85(7), 3574-3582. https://doi.org/10.1097/MS9.0000000000000903
45. Signorelli, F., Balbi, G. G. M., Domingues, V., & Levy, R. A. (2018). New and upcoming treatments in antiphospholipid syndrome: A comprehensive review. Pharmacological Research, 133, 108–120. https://doi.org/10.1016/j.phrs.2018.04.012
46. Takahashi, H., & Echizen, H. (2003). Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. The Pharmacogenomics Journal, 3(4), 202–214. https://doi.org/10.1038/sj.tpj.6500182
47. Tay, K. H., Shantsila, E., & Lip, G. Y. H. (2013). The Coagulation Pathway and Approaches to Anticoagulation. In G. Y. Lip & E. Shantsila (Eds.), Handbook of Oral Anticoagulation (pp. 1–5). Springer Healthcare Ltd. https://doi.org/10.1007/978-1-908517-96-8_1
48. Thijssen, H. H. W. (1995). Warfarin-based rodenticides: Mode of action and mechanism of resistance. Pesticide Science, 43(1), 73–78. https://doi.org/10.1002/ps.2780430112
49. Tomaselli, G. F., Mahaffey, K. W., Cuker, A., Dobesh, P. P., Doherty, J. U., Eikelboom, J. W., Florido, R., Gluckman, T. J., Hucker, W. J., Mehran, R., Mess, é S. R., Perino, A. C., Rodriguez, F., Sarode, R., Siegal, D. M., & Wiggins, B. S. (2020). 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. Journal of the American College of Cardiology, 76(5), 594–622. https://doi.org/10.1016/j.jacc.2020.04.053
50. Tran, H., Joseph, J., Young, L., McRae, S., Curnow, J., Nandurkar, H., Wood, P., & McLintock, C. (2014). New oral anticoagulants: A practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Internal Medicine Journal, 44(6), 525–536. https://doi.org/10.1111/imj.12448
51. Tran, H. A., Chunilal, S. D., Harper, P. L., Tran, H., Wood, E. M., & Gallus, A. S. (2013). An update of consensus guidelines for warfarin reversal. Medical Journal of Australia, 198(4), 198–199. https://doi.org/10.5694/mja12.10614
52. U.S. Food & Drug Administration. (2 June, 2018). Generic Enoxaparin Questions and Answers. FDA. Retrieved from: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/generic-enoxaparin-questions-and-answers
53. van Ryn, J., Goss, A., Hauel, N., Wienen, W., Priepke, H., Nar, H., & Clemens, A. (2013). The Discovery of Dabigatran Etexilate. Frontiers in Pharmacology, 4, 12. https://doi.org/10.3389/fphar.2013.00012
54. Vardanyan, R. S., & Hruby, V. J. (2006). 24—Anticoagulants, Antiaggregants, Thrombolytics, and Hemostatics. In R. S. Vardanyan & V. J. Hruby (Eds.), Synthesis of Essential Drugs (pp. 323–335). Elsevier. https://doi.org/10.1016/B978-044452166-8/50024-8
55. Wadelius, M., Sörlin, K., Wallerman, O., Karlsson, J., Yue, Q.-Y., Magnusson, P. K. E., Wadelius, C., & Melhus, H. (2004). Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. The Pharmacogenomics Journal, 4(1), 40–48. https://doi.org/10.1038/sj.tpj.6500220
56. Zhao, H.-P., Jiang, H.-M., & Xiang, B.-R. (2013). Discontinued drugs in 2012: Cardiovascular drugs. Expert Opinion on Investigational Drugs, 22(11), 1437–1451. https://doi.org/10.1517/13543784.2013.832198
57. Zhou, Q., Wang, Z., Wang, H., Chen, Z., Li, X., Dai, X., Zhang, Y., Yu, X., Zhou, R., & Hu, W. (2023). Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial. American Journal of Cardiovascular Drugs, 23(1), 101–112. https://doi.org/10.1007/s40256-022-00562-5

I have taken the time to research relevant medical journals, and also share my personal experiences where appropriate. I hope you find it useful, whether as a patient or as a supporter. If there are specific terms used in this post that you were wondering about, such as antiphospholipid antibodies (aPLs), correlations with other autoimmune diseases such as Lupus, the reversal protocol and more, then I’d recommend that you check out the complete A – Z guide plus other resources in the series below.

Antiphospholipid Syndrome Diagnosis: The A – Z Guide as a Patient

Read Related Posts in the Antiphospholipid Syndrome Diagnosis Series:
• Latest Research on Antiphospholipid Syndrome (2024 Edition)
• The Lowdown on Medications & Antiphospholipid Syndrome (Warfarin, Enoxaparin, DOACs, NSAIDs & More)
• How Does Antiphospholipid Syndrome Affect The Body? (Beyond the Blood to Major Organs)
• The Annoying Thing About Living with Antiphospholipid Syndrome (My Personal Experiences)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• What it Feels Like to be Refused Treatment by a Hospital’s A&E / ER

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

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Women’s Health in Antiphospholipid Syndrome

The terms for ‘women’ and ‘female’ used in this article will mostly be referring to those who were assigned female at birth, and will take into account genetic differences and their links with autoimmunity. Females typically have two X chromosomes, whereas males have an X and Y chromosome. Females account for around 80% of all autoimmune disease cases as well, and recent studies have shown that specific X-linked genes may be contributors to autoimmune disease. According to Dou et al. (2024):

“To make the gene expression output roughly equivalent between females and males, every cell in a female’s body epigenetically silences one of two X chromosomes via the action of the long non-coding RNA (lncRNA) Xist. Xist is an ∼17-kb lncRNA (19 kb in human) that is transcribed only from the inactive X chromosome and thus not expressed in males.”

Whilst exactly how, when and where is still sketchy, there is no doubt that there can be further Antiphospholipid Syndrome related complications simply by being female. After all, APS is a blood clotting autoimmune disorder, and as women we get periods every month on average, and also need to go through the pregnancy process if we so choose to – all of which involves the immune system and blood.

Epidemiology of APS – Males vs Females

Antiphospholipid Syndrome is more commonly found in women than in men, with a ratio of about 3.5:1. It is also more often secondary APS (SAPS) in women, whereas men are more prone to primary APS (PAPS). Women present with strokes, livedo and headaches more frequently than in men. Whereas male PAPS patients present more with myocardial infarction, mesenteric and hepatic vein thrombosis (Kaul and Hughes, 2023).

Other studies have also shown greater cerebrovascular disease in women, whilst men had gastrointestinal involvement more frequently (Jara et al., 2005). This is also an interesting table which shows the comorbidities associated with APS and antiphospholipid antibodies (aPLs) positivity in the general population, from a compilation of various research papers (p.s. link sometimes needs to be clicked twice to open for some unknown reason). It includes the various aPLs found in women in different types of pregnancy incidents, ages when women first experienced a stroke, patients with comorbidities, and more (Dabit et al., 2021).

Read this post for more information on how Antiphospholipid Syndrome can affect the entire body.

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Menstruation & Antiphospholipid Syndrome

It is not unusual for us ladies to experience heavier periods whilst taking anticoagulants, or to see some blood clots discharged. Something important to know about are ovarian cysts. Most of these cysts are common and harmless, and occur even in healthy women. They usually get reabsorbed into the body or are passed out, but sometimes they can rupture.

When this happens, it is called an Ovarian Cyst Rupture, and I can tell you from two first-hand experiences that it is not pleasant. I nearly died both times. This was also the reason why my healthcare team decided to put me on birth control (Nexplanon), to prevent further episodes. A benefit of being on birth control, at least for me, is that I have experienced lighter periods with fewer period cramps since then.

The Relation Between Oestrogen & APS

Or estrogen, depending on where you come from! Oestrogen is a steroid hormone associated with menstruation (Delgado and Lopez-Ojeda, 2023). There are a few different types – estrone (E1), estradiol (E2), estriol (E3), and etestrol (E4) – and they collectively regulate the development and function of the female reproductive system. Males also produce oestrogen, primarily in the testis (Harding and Heaton, 2022).

Beyond its role as a sex hormone, oestrogens and their receptors also play a role in modulating innate immune responses against infections, from viral to bacterial, parasitic and fungal. They display anti-inflammatory effects and also help the body with wound healing and repair (Harding and Heaton, 2022). A powerful hormone, no doubt!

However, oestrogen also plays a role in pain flares for rheumatoid autoimmune disorders, such as SLE (Lupus) and Rheumatoid Arthritis. Oestrogens also increase the risk of both arterial and venous thrombosis, and have effects on almost every cell in the body. The technical explanation, according to Abou-Ismail et al. (2020):

“Estrogen leads to increased thrombin generation and fibrin clot formation by increasing the levels of variable coagulation proteins and decreasing the levels of anticoagulant proteins.”

And according to Manukyan et al. (2020):

“Our findings show the ability of E2 [high-17β-estradiol] to promote proinflammatory and procoagulatory phenotype of innate immune cells in individuals with aPL [antiphospholipid antibodies] positivity. Our data highlights the significant impact of female hormones on the activation of immune cells in the presence of aPL.”

Oestrogen also increases the risk of blood clots when used in contraceptives or as postmenopausal hormone replacement therapy. This can also happen in men who use them as treatment for coronary disease, or in sex-change treatment (Rosendaal et al., 2002). Thus, it is best to avoid treatments and forms of contraception that contain oestrogen if you have Antiphospholipid Syndrome.

Ovarian Cyst Ruptures in Women with Antiphospholipid Syndrome

Ovarian cyst ruptures are extremely painful and can be life-threatening. For women with Antiphospholipid Syndrome who are on some form of anticoagulation treatment, the blood thinning effects of the medication(s) can compound the problem. Let’s take a closer look at how and why they happen.

Types of Functional Cysts

There are two types of functional cysts that your ovaries grow every month – a follicle cyst and a corpus luteum cyst. A follicular cyst occurs when the follicle doesn’t rupture during ovulation. A corpus luteum cyst occurs after the egg is released, and the opening becomes blocked in the corpus luteum. Most functional ovarian cysts are harmless and resolve on their own.

However, an ovarian cyst rupture can occur sometimes during menstruation. For a healthy female, usually this gets passed out as a blood clot, or reabsorbed by the body, with few to no incidences. If there are symptoms, they may include sudden abdominal or pelvic pain, pain with fever and vomiting, or signs of shock and weakness.

Hemoperitoneum in Females with APS

For a female with Antiphospholipid Syndrome, such ruptures can sometimes cause internal bleeding, no thanks to their blood thinning medications. This is also known as a hemoperitoneum, where excess blood accumulates in the abdominal or pelvic cavity, and it is a medical emergency.

This doesn’t happen every period of course, but I’ve been unlucky to have had two ovarian cyst rupture episodes that were of life-threatening status. The pain was acute and came on suddenly. Within 4 hours I was doubled over, swollen and bloated with pain, and had to crawl to the hospital.

They will usually do an abdominal ultrasound at the A&E/ER to check for free fluid. Emergency surgery is usually required, but generally avoided for patients who are on anticoagulants, until the blood thinning effects of their medications have been counteracted.

The second time I had an ovarian cyst rupture, the nurses at the A&E were rather junior, so I had to insist on the ultrasound. The senior doctor later confirmed the diagnosis, and I was immediately placed in the high emergency section, given strong painkillers, and injected with three different types of blood clotting agents. RBC (red blood cell) counts may fall, but this can be due to dehydration as well.

Read this post for more information on reversal agents and medications related to Antiphospholipid Syndrome.

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Birth Control as Prevention for Bleeding Risk in Women with Antiphospholipid Syndrome

As a result of these ovarian cyst rupture episodes, my gynaecologist suggested birth control to prevent ovulation, which would reduce the chances of a reoccurrence.

There are a few types of birth controls, and they contain the hormones oestrogen, or progestin, or both. As mentioned previously, oestrogen increases the risk of blood clots. Studies have also demonstrated that progestins in combination oral contraceptives also play a role to a lesser degree (Rosendaal, 2002). You can view a table of contraceptive recommendations for women with APS here (Sammaritano, 2021).

As I have many comorbidities such as Lupus and Sjögren’s disease and am severely immunocompromised, my gynaecologist did not recommend intrauterine devices (IUDs) either due to the higher chance for infections. I personally use Nexplanon, as suggested by my own gynaecologist.

Etonogestrel (Implanon & Nexplanon) – What I Use for Birth Control as a Female with APS

Etonogestrel is a progestin hormone under the brand names of Implanon and Nexplanon. It comes in the form of a small implant, and your gynaecologist will make a small cut in your arm to insert it subdermally. You will most likely need to do a reversal of your blood thinning medication beforehand, just in case of excessive bleeding. Your rheumatologist/doctor and gynaecologist will work closely with you to do the reversal protocol, which you can read more about here.

What I like about the etonogestrel implant is that once it’s inserted, it lasts for 3 years and you can go about your life as per usual. And should you wish to try for pregnancy, you can simply remove it and start trying pretty much immediately.

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Pregnancy with Antiphospholipid Syndrome

Pregnancy is a tricky and touchy topic when it comes to Antiphospholipid Syndrome. I’ve known people who have had miscarriages at 8 months, because they didn’t know that they had APS. The incidence of pregnancy loss for women with Antiphospholipid Syndrome is reported to be between 34% – 76% (Xu et al., 2019).

Women with APS need to work closely with their rheumatologist, a high-risk gynaecologist, and their entire healthcare team – before even getting pregnant. Your healthcare team should assess your risk factors, and work with you to implement preventive strategies, as well as come up with a plan that is tailored to your specific circumstances and health status (Andreoli et al., 2017).

So Why Not Screen Every Woman Before Pregnancy for Antiphospholipid Antibodies?

I used to think that every woman should be tested for APS before pregnancy to save us the grief of a miscarriage. But having done more research, I can understand why it isn’t such a good idea to do so. In general, asymptomatic patients should not be screened for aPLs as there is a risk of false positivity of up to 3 – 20% (Rand and Wolgast, 2012). This not only subjects the individual to unnecessary treatment, but increases the risk of bleeding complications.

Before screening for aPLs, the patient’s medical history (such as recurrent miscarriages), as well as comorbidities (such as SLE), need to make sense medically too. False positive aPLs tests can also be triggered by many types of infections, such as Lyme Disease, Syphilis and EBV (Rand and Wolgast, 2012).

Will I Pass Antiphospholipid Syndrome on to My Child?

Like many other autoimmune diseases, Antiphospholipid Syndrome is polygenic, where multiple genes are involved, and can also be influenced by environmental factors. The individual contribution of each gene may even be unnoticeable, and requires multiple contributing factors to activate (Lvovs et al., 2012). Whilst yes, the genes are still there, APS is not commonly inherited from parent to child, as compared to other conditions such as sickle cell anaemia or cystic fibrosis.

According to Barinotti et al. (2020):

“The etiology of APS is still unknown, but similarly to other autoimmune diseases, it seems to be linked to a complex interplay between genetic predisposition, antigenic stimuli, and the presence of specific autoantibodies.” ….. “APS is a complex rare disease with the great majority of the cases being sporadic. Rarely, the condition has been reported to run in families.”

There is still much to be understood as to how Antiphospholipid Syndrome ultimately develops, but according to Ortiz-Fernández and Sawalha (2019), recent studies have identified some of the genetic components that contribute to APS, such as: “antigen receptor-mediated signaling, interferon-gamma-mediated signaling, T cell receptor signaling, and regulation of B cell receptor signaling pathways”. Genetic susceptibility to APS is also dependent on ethnic, gene-gene, gene-environment, and a multitude of other factors that are still not completely understood (Horita and Merrill, 2004).

Medication Interactions During Pregnancy with Antiphospholipid Syndrome

It is important to inform your medical team before even trying for pregnancy, as certain medications that you’re on might be harmful to either yourself or the foetus. Some medications take a while to be completely eradicated from your bodily system as well. Your doctor will usually switch you to a safer alternative for pregnancy, and monitor you closely for adverse effects.

Here are some important medications to take note of in relation to APS and pregnancy. If you have other medications that you take for other chronic illnesses, they should also be taken into account.

Warfarin & Pregnancy

Warfarin medication should be paused during pregnancy, as it can be harmful to foetuses. Apart from a rare disease called Foetal Warfarin Syndrome (Starling et al., 2012), warfarin can also cause other complications during pregnancy such as developmental problems or haemorrhages (Abadi et al., 2002).

Hydroxychloroquine, Low Molecular Weight Heparin (LMWH) & Aspirin in Pregnant APS Patients

Recent studies have also shown that the current standard for pregnancy in APS patients, which uses aspirin and LMWH, are limited in efficacy of late-term pregnancy complications. Interestingly, hydroxychloroquine, which is an anti-malarial drug commonly used to treat Lupus (SLE), showed benefits for APS patients in pregnancy.

A study on 176 pregnancies (96 with aPLs) reflected a higher rate of live births, and a lower prevalence of aPLs-related pregnancy morbidity whilst on hydroxychloroquine (Sciascia et al., 2016). Another European multicentre study of 35 APS patients who were put on hydroxychloroquine, showed a decrease in pregnancy losses from 81% to 19%, as compared to previous usage of aspirin and/or LMWH only (Mekinian, 2015).

These findings by Marchetti et al. (2014) explain why hydroxychloroquine may be beneficial for APS patients who are pregnant:

“Here, we observed that HCQ completely reversed the effects of the plasma of APS patients (free from anti–annexin V antibodies) and the anti‐β2GP1 antibodies on trophoblastic cell fusion and differentiation.”

Something interesting I found whilst doing research on this topic, is that in Japan, APS-complicated pregnancies from the usage of LMWH is not covered by medical insurance. Thus, unfractionated heparin (UFH) and/or low-dose aspirin (LDA) are used instead (Deguchi et al., 2017). In addition, there is also something known as aspirin-heparin resistant APS (AHRAPS), where other therapies such as high-dose intravenous immunoglobulin (IVIG) may need to be included (Arumugham and Rayi, 2023).

Should you be interested to learn more, this paper by Schreiber and Hunt (2019) does an excellent job of listing out the management of APS during pregnancy. You can also learn more about warfarin, LMWH and other medications related to APS in this post.

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Pregnancy Complications with Antiphospholipid Syndrome

Whilst it is important not to worry yourself sick(er), it is also important to be aware of potential pregnancy complications as a result of Antiphospholipid Syndrome, in order to better care and advocate for yourself. These complications can arise from a combination of factors – from the disease itself, comorbidities, hormonal changes, decreased mobility, stage of pregnancy, and method of delivery, with caesarean section carrying a higher risk of thrombosis than vaginal delivery (Lee et al., 2021).

Whilst there are certain guidelines sketched out for the management of APS during pregnancy, more studies still need to be done in order to determine the best course of action. Thus, it is critical to ensure that your pregnancy care is individualised based on your medical history, comorbidities such as SLE, lifestyle factors and more.

Trophoblasts

Pregnancy complications do not just stem from a single factor; Antiphospholipid Syndrome can attack from different pathways. For one, they can interact with trophoblasts, which interfere with nutrients transmitted to the embryo in the placenta. Apart from nutrients, trophoblasts also produce numerous growth factors and hormones that support healthy foetal and placental development (Wang and Zhao, 2010).

According to a study by Mulla et al. (2009):

“Our findings suggest that early pregnancy loss and late obstetric complications in APS may arise from anti-β2GPI Abs acting on first trimester trophoblast cells, thereby triggering placental inflammation and cell death.”

Meaning to say that antiphospholipid antibodies trigger an inflammatory response in the placenta, which interferes with trophoblasts. Studies have found that hydroxychloroquine, an anti-malarial drug commonly used to treat Lupus (SLE), has beneficial effects against this.

Preeclampsia

Preeclampsia is also associated with Antiphospholipid Syndrome, and can also be associated with shallow cytotrophoblast invasion (Skoura et al., 2022). Preeclampsia manifests as hypertension and sometimes with protein in the urine (proteinuria). It is vital to work with your obstetrician closely, as this can be a deadly condition.

Venous Thromboembolism (VTE)

Another severe complication of pregnancy for APS patients is venous thromboembolism (VTE), especially in the legs (DVTs). This can manifest systemically with mild to life-threatening symptoms, from pain and swelling, to blood clots in the lungs (pulmonary embolism). Left-sided DVTs are also more common at 70% – 90%, due to the involvement of certain veins during pregnancy. VTE is also still a risk during the postpartum period (Varrias et al., 2023).

In general, LMWH is used for the prevention and treatment of VTEs in pregnant women, although that depends on the individual as well. Here are some guidelines based on observational studies and extrapolation from Bates et al. (2012).

Read more about cardiovascular and pulmonary embolisms in general relation to APS here.

Intrauterine Growth Restriction (IUGR)

Intrauterine Growth Restriction (IUGR) – also known as Foetal Growth Restriction – is another pregnancy complication with APS, where the foetus is estimated to be below the 10th percentile for its gestational age. Women with APS were found to have a higher rate of IUGR, with anticardiolipin (aCL) positivity highly associated with it (Xi et al., 2020).

In another systematic meta-analysis, anticardiolipin antibodies (aCLs) and anti-beta2 glycoprotein 1 antibodies (anti-β2GP1) were also found to be associated with IUGR, whilst lupus anticoagulant (LA) did not increase the chances of it (Xu et al., 2022). This further demonstrates the complexity of antiphospholipid antibodies and APS in general, as each type of antibody affects the body differently, yet are all indicators towards an Antiphospholipid Syndrome diagnosis.

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Miscarriages & Antiphospholipid Syndrome

Sadly, many women only discover that they have Antiphospholipid Syndrome after recurrent miscarriages. According to Di Prima et al. (2011):

“Obstetric complications are the hallmark of antiphospholipid syndrome. Recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, Foetal distress, Foetal or neonatal thrombosis, pre-eclampsia/eclampsia, HELLP syndrome, arterial or venous thrombosis and placental insufficiency are the most severe APS-related complication for pregnant women.”

Foetal loss over 10 weeks of gestation is more common in women with Antiphospholipid Syndrome, although about half of recurrent miscarriages occur during the first trimester. The lupus anticoagulant also plays a big role in recurrent miscarriages before the 24th week of gestation (Di Prima et al., 2011).

The rate of successful births is more than 80% although there are still risks, such as preeclampsia and preterm delivery (Abrahams et al., 2017). I can’t emphasise this enough, but it is extremely important to work closely with a high-risk obstetrician and your entire healthcare team throughout your pregnancy journey.

The Stigma Associated with Women’s Health in Antiphospholipid Syndrome, and the Perceived Inability to Conceive

I have always known that I want to be a mother – since I was 14 in fact. In my young teenage mind, I would get married at 27, have a few children, and devote myself to bringing them up as well as I can. I was prepared to suffer through all pains and risks to do so. Unfortunately, life doesn’t work that way. It is not to be dictated – it sets the direction and pace, and you can either choose to adapt, or struggle double.

I am now 38, with neither partner nor child. My biological clock is ticking, but there is nothing I can do about it. After all, marriage and/or pregnancy takes two hands to clap. Partners and potential partners have also written me off due to my multitude of chronic illnesses; they do not even want to begin with the slightest possibility of me being unable to conceive.

This is a phenomenological study that might resonate with you, if you have experienced foetal loss as a woman with Antiphospholipid Syndrome (Mahmoud et al., 2020). It illustrates the social burdens felt by patients, with some marriages ending in divorce due to expectations from husbands and mother-in-laws. The psychological suffering of the patient is huge as well, with many women feeling sad and frustrated. Some choose to delay subsequent pregnancies, and many live in constant fear due to the unpredictability.

It is important for healthcare professionals to educate their patients on potential complications, from the physical to emotional. In my opinion, it is also the responsibility of loved ones to educate themselves on women’s health in Antiphospholipid Syndrome, and to understand that it is not their partner’s fault. As a patient, know that you are not alone, and that you are not to be blamed.

Read Related Posts:
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• Loss of Identity with Chronic Illness & The Plot Twist: Sharpened Self-Worth
• Sometimes, Physical Pain Isn’t the Worst Part About Chronic Illness
• Life with Chronic Illness: Happiness & Pain Can Co-exist

Ongoing Research on Recurrent Miscarriages in APS

A systematic review and meta-analysis has been done to try and determine which antiphospholipid antibodies play a bigger role in recurrent miscarriages for female patients with APS. Whilst it has been found that anticardiolipin antibodies, lupus anticoagulant, anti-β2-glycoprotein I antibodies and antiphosphatidylserine (which is just about all of them…) are related to recurrent miscarriages, more studies still need to be done to learn more about what they truly do (da Silva Santos et al., 2017).

Up to 15% of unexplained stillbirths might be due to aPLs (antiphospholipid antibodies), with women with lupus anticoagulant or who are ‘triple apL positive’ at the highest risk (Herrera et al., 2017).

Menopause and Antiphospholipid Syndrome

There are not many studies done on APS and menopause but in general, menopause is a period of immune changes within the female body, amongst other events. Levels of oestrogen and DHEA sulfate decrease, which may lead to: an increase in proinflammatory cytokines, a decrease in certain anti-inflammatory cytokines, decreased lymphocyte levels (CD4+ T cells and B cells), and a decrease in cytotoxic activity of NK cells (Bove, 2013).

Depending on the individual, type of autoimmune diseases they have, and other factors such as epigenetics and environment, the menopause transition can occur quite differently. There are some reports of decreased frequency of pain flares in patients with SLE, yet at the same time, greater damage accrual in affected organs (Bove, 2013).

In one controlled study, premenopausal women with APS/SLE were also found to have an increased risk of atherosclerosis, which is a buildup of fats, cholesterol and other substances in and on the artery walls (Vlachoyiannopoulos et al., 2003). As per Mayo Clinic, whilst atherosclerosis is often considered a heart problem, it can also occur in any other artery in the human body. The plaque not only cause the arteries to narrow, they may also burst and lead to blood clots. Learn more about cardiovascular manifestations in APS patients here.

Conclusion to Women’s Health in Antiphospholipid Syndrome

I hope that this article provides you with the added knowledge to better care for yourself as a female with Antiphospholipid Syndrome. From menstruation to child birth to menopause – the journey of womanhood is intertwined with blood, so it’s vital to be aware of how APS can interact with each stage of your life.

Should you have any questions, corrections, experiences, or more knowledge to share – feel free to leave a comment below so we can all learn together. Don’t forget to check out the other posts in the series listed below, too!

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Read Related Posts in the Antiphospholipid Syndrome Diagnosis Series:
• Antiphospholipid Syndrome Diagnosis: The A to Z Guide as a Patient
• Latest Research on Antiphospholipid Syndrome (2024 Edition)
• The Lowdown on Medications & Antiphospholipid Syndrome (Warfarin, Enoxaparin, DOACs, NSAIDs & More)
• How Does Antiphospholipid Syndrome Affect The Body? (Beyond the Blood to Major Organs)
• The Annoying Thing About Living with Antiphospholipid Syndrome (My Personal Experiences)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• What it Feels Like to be Refused Treatment by a Hospital’s A&E / ER

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References:

1. Abadi, S., Einarson, A., & Koren, G. (2002). Use of warfarin during pregnancy. Canadian Family Physician, 48(4), 695-697. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/12046363
2. Abou-Ismail, M. Y., Sridhar, D. C., & Nayak, L. (2020). Estrogen and thrombosis: a bench to bedside review. Thrombosis research, 192, 40-51. https://doi.org/10.1016/j.thromres.2020.05.008
3. Abrahams, V. M., Chamley, L. W., & Salmon, J. E. (2017). Emerging Treatment Models in Rheumatology: Antiphospholipid Syndrome and Pregnancy: Pathogenesis to Translation. Arthritis & Rheumatology, 69(9), 1710–1721. https://doi.org/10.1002/art.40136
4. Andreoli, L., Bertsias, G. K., Agmon-Levin, N., Brown, S., Cervera, R., Costedoat-Chalumeau, N., Doria, A., Fischer-Betz, R., Forger, F., Moraes-Fontes, M. F., Khamashta, M., King, J., Lojacono, A., Marchiori, F., Meroni, P. L., Mosca, M., Motta, M., Ostensen, M., Pamfil, C., … Tincani, A. (2017). EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Annals of the Rheumatic Diseases, 76(3), 476–485. https://doi.org/10.1136/annrheumdis-2016-209770
5. APS Support UK. (n.d.). APS and Women’s Health. APS Support UK. Retrieved from: https://aps-support.org.uk/self-help/living-with-aps/aps-and-womens-health
6. Arumugham, V. B., & Rayi, A. (2023). Intravenous immunoglobulin (IVIG). In StatPearls [Internet]. StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK554446/
7. Bates, S. M., Greer, I. A., Middeldorp, S., Veenstra, D. L., Prabulos, A. M., & Vandvik, P. O. (2012). VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2), e691S–e736S. https://doi.org/10.1378/chest.11-2300
8. Barinotti, A., Radin, M., Cecchi, I., Foddai, S. G., Rubini, E., Roccatello, D., Sciascia, S., & Menegatti, E. (2020). Genetic Factors in Antiphospholipid Syndrome: Preliminary Experience with Whole Exome Sequencing. International journal of molecular sciences, 21(24), 9551. https://doi.org/10.3390/ijms21249551
9. Bove, R. (2013). Autoimmune diseases and reproductive aging. Clinical Immunology, 149(2), 251-264. https://doi.org/10.1016/j.clim.2013.02.010
10. Cleveland Clinic. (2023). Hemoperitoneum. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/hemoperitoneum
11. Cleveland Clinic. (2022). Intrauterine Device (IUD). Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/treatments/24441-intrauterine-device-iud
12. Cleveland Clinic. (2022). Intrauterine Growth Restriction. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/24017-intrauterine-growth-restriction
13. Cleveland Clinic. (n.d.). Etonogestrel Implant. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/drugs/18407-etonogestrel-implant
14. Cunha, J. P. (Ed.). (2022). Implanon. RxList. Retrieved from: https://www.rxlist.com/implanon-drug.htm
15. Dabit, J. Y., Valenzuela-Almada, M. O., Vallejo-Ramos, S., & Duarte-García, A. (2021). Epidemiology of antiphospholipid syndrome in the general population. Current rheumatology reports, 23(12), 85. https://doi.org/10.1007/s11926-021-01038-2
16. da Silva Santos, T., Ieque, A. L., de Carvalho, H. C., Sell, A. M., Lonardoni, M. V. C., Demarchi, I. G., … & Teixeira, J. J. V. (2017). Antiphospholipid syndrome and recurrent miscarriage: A systematic review and meta-analysis. Journal of reproductive immunology, 123, 78-87. https://doi.org/10.1016/j.jri.2017.09.007
17. Deguchi, M., Yamada, H., Sugiura-Ogasawara, M., Morikawa, M., Fujita, D., Miki, A., … & Murashima, A. (2017). Factors associated with adverse pregnancy outcomes in women with antiphospholipid syndrome: a multicenter study. Journal of reproductive immunology, 122, 21-27. https://doi.org/10.1016/j.jri.2017.08.001
18. Delgado, B. J., & Lopez-Ojeda, W. (2023). Estrogen. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK538260/
19. Di Prima, F. A., Valenti, O., Hyseni, E., Giorgio, E., Faraci, M., Renda, E., De Domenico, R., & Monte, S. (2011). Antiphospholipid Syndrome during pregnancy: the state of the art. Journal of prenatal medicine, 5(2), 41–53. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165/
20. Dou, D. R., Zhao, Y., Belk, J. A., Zhao, Y., Casey, K. M., Chen, D. C., … & Chang, H. Y. (2024). Xist ribonucleoproteins promote female sex-biased autoimmunity. Cell, 187(3), 733-749. https://doi.org/10.1016/j.cell.2023.12.037
21. Graham, F. (2024). Daily briefing: Autoimmune disease linked to X chromosome. Nature. Retrieved from: https://www.nature.com/articles/d41586-024-00342-y
22. Harding, A. T., & Heaton, N. S. (2022). The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection. Cancers, 14(4), 909. https://doi.org/10.3390/cancers14040909
23. Herrera, C. A., Heuser, C. C., & Branch, D. W. (2017). Stillbirth: the impact of antiphospholipid syndrome?. Lupus, 26(3), 237-239. https://doi.org/10.1177/0961203316671815
24. Hindorff, L. (2024). Polygenic Trait. National Human Genome Research Institute. Retrieved from: https://www.genome.gov/genetics-glossary/Polygenic-Trait
25. Horita, T., & Merrill, J. T. (2004). Genetics of antiphospholipid syndrome. Current rheumatology reports, 6(6), 458–462. https://doi.org/10.1007/s11926-004-0025-0
26. Jara, L. J., Medina, G., Vera-Lastra, O., & Barile, L. (2005). The impact of gender on clinical manifestations of primary antiphospholipid syndrome. Lupus, 14(8), 607-612. https://doi.org/10.1191/0961203305lu2176oa
27. Kaul, A., Jawad, A., & Hughes, G. (2023). Antiphospholipid syndrome, thrombosis and multidisciplinary management. Trends in Urology & Men’s Health, 14(3), 31-35. https://doi.org/10.1002/tre.911
28. Lee, E. E., Jun, J. K., & Lee, E. B. (2021). Management of women with antiphospholipid antibodies or antiphospholipid syndrome during pregnancy. Journal of Korean Medical Science, 36(4). https://doi.org/10.3346/jkms.2021.36.e24
29. Lvovs, D., Favorova, O. O., & Favorov, A. V. (2012). A Polygenic Approach to the Study 
of Polygenic Diseases. Acta naturae, 4(3), 59–71. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491892/
30. Mekinian, A., Lazzaroni, M. G., Kuzenko, A., Alijotas-Reig, J., Ruffatti, A., Levy, P., … & Fain, O. (2015). The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmunity reviews, 14(6), 498-502. https://doi.org/10.1016/j.autrev.2015.01.012
31. Mahmoud, F. Z., Elsayed, Y. A., & Eswi, A. S. (2020). The Lived Experience of Hospitalized Pregnant Women Having Antiphospholipid Syndrome with a Previous Fetal Loss: A Phenomenological Study. Rehabilitation, 5(1), 5-11. https://doi.org/10.11648/j.rs.20200501.12
32. Manukyan, G., Martirosyan, A., Slavik, L., Ulehlova, J., Dihel, M., Papajik, T., & Kriegova, E. (2020). 17β-Estradiol Promotes Proinflammatory and Procoagulatory Phenotype of Innate Immune Cells in the Presence of Antiphospholipid Antibodies. Biomedicines, 8(6), 162. https://doi.org/10.3390/biomedicines8060162
33. Marchetti, T., Ruffatti, A., Wuillemin, C., De Moerloose, P., & Cohen, M. (2014). Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies. Journal of Thrombosis and Haemostasis, 12(6), 910-920. https://doi.org/10.1111/jth.12570
34. Mayo Clinic. (2023). Ovarian cysts. Mayo Clinic. Retrieved from: https://www.mayoclinic.org/diseases-conditions/ovarian-cysts/symptoms-causes/syc-20353405
35. Mayo Clinic. (2022). Arteriosclerosis / atherosclerosis. Mayo Clinic. Retrieved from: https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/symptoms-causes/syc-20350569
36. Mulla, M. J., Brosens, J. J., Chamley, L. W., Giles, I., Pericleous, C., Rahman, A., … & Abrahams, V. M. (2009). Antiphospholipid antibodies induce a pro‐inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. American Journal of Reproductive Immunology, 62(2), 96-111. https://doi.org/10.1111/j.1600-0897.2009.00717.x
37. NHS. (2022). Pregnancy, breastfeeding and fertility while taking warfarin. NHS. Retrieved from: https://www.nhs.uk/medicines/warfarin/pregnancy-breastfeeding-and-fertility-while-taking-warfarin/
38. Ortiz-Fernández, L., & Sawalha, A. H. (2019). Genetics of Antiphospholipid Syndrome. Current Rheumatology Reports, 21(12), 65. https://doi.org/10.1007/s11926-019-0869-y
39. Rand, J. H., & Wolgast, L. R. (2012). Dos and don’ts in diagnosing antiphospholipid syndrome. Hematology 2010, the American Society of Hematology Education Program Book, 2012(1), 455-459. https://doi.org/10.1182/asheducation.V2012.1.455.3806865
40. Rosendaal, F. R., Helmerhorst, F. M., & Vandenbroucke, J. P. (2002). Female hormones and thrombosis. Arteriosclerosis, thrombosis, and vascular biology, 22(2), 201-210. https://doi.org/10.1161/hq0202.102318
41. Sammaritano, L. R. (2021). Which hormones and contraception for women with APS? Exogenous hormone use in women with APS. Current Rheumatology Reports, 23(6), 44. https://doi.org/10.1007/s11926-021-01006-w
42. Schreiber, K., & Hunt, B. J. (2019). Managing antiphospholipid syndrome in pregnancy. Thrombosis research, 181, S41-S46. https://doi.org/10.1016/S0049-3848(19)30366-4
43. Sciascia, S., Hunt, B. J., Talavera-Garcia, E., Lliso, G., Khamashta, M., & Cuadrado, M. J. (2016). The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. American journal of obstetrics and gynecology, 214(2), 273-e1. https://doi.org/10.1016/j.ajog.2015.09.078
44. Skoura, R., Andronikidi, P. E., Anestakis, D., Petanidis, S., Orovou, E., Tzitiridou, M., & Eskitzis, P. (2022). Antiphospholipid Syndrome and Preeclampsia in Pregnancy: A Case Report. Cureus, 14(8), e28458. https://doi.org/10.7759/cureus.28458
45. Starling, L. D., Sinha, A., Boyd, D., & Furck, A. (2012). Fetal warfarin syndrome. Case Reports, 2012, bcr2012007344. https://doi.org/10.1136/bcr-2012-007344
46. Varrias, D., Spanos, M., Kokkinidis, D. G., Zoumpourlis, P., & Kalaitzopoulos, D. R. (2023). Venous Thromboembolism in Pregnancy: Challenges and Solutions. Vascular health and risk management, 19, 469–484. https://doi.org/10.2147/VHRM.S404537
47. Vlachoyiannopoulos, P. G., Kanellopoulos, P. G., Ioannidis, J. P. A., Tektonidou, M. G., Mastorakou, I., & Moutsopoulos, H. M. (2003). Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Rheumatology, 42(5), 645-651. https://doi.org/10.1093/rheumatology/keg182
48. Wang, Y., & Zhao, S. (2010). Chapter 4 – Cell types of the placenta. In: Vascular biology of the placenta. Morgan & Claypool Life Sciences. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK53245/
49. Xi, F., Cai, Y., Lv, M., Jiang, Y., Zhou, F., Chen, Y., … & Luo, Q. (2020). Anticardiolipin positivity is highly associated with intrauterine growth restriction in women with antiphospholipid syndrome. Clinical and Applied Thrombosis/Hemostasis, 26, 1076029620974455. https://doi.org/10.1177/1076029620974455
50. Xu, J., Chen, D., Tian, Y., Wang, X., & Peng, B. (2022). Antiphospholipid Antibodies Increase the Risk of Fetal Growth Restriction: A Systematic Meta-Analysis. International journal of clinical practice, 2022, 4308470. https://doi.org/10.1155/2022/4308470
51. Xu, J., Chen, D., Duan, X., Li, L., Tang, Y., & Peng, B. (2019). The association between antiphospholipid antibodies and late fetal loss: A systematic review and meta‐analysis. Acta obstetricia et gynecologica Scandinavica, 98(12), 1523-1533. https://doi.org/10.1111/aogs.13665
52. Yu, R. Z. (2021). Is Antiphospholipid Syndrome (APS) Hereditary? If I Have APS, Should My Family Members Be Tested? Michigan Medicine, University of Michigan. Retrieved from: https://medicine.umich.edu/dept/intmed/antiphospholipid-syndrome-aps-hereditary-if-i-have-aps-should-my-family-members-be-tested

The bad news about Antiphospholipid Syndrome (APS) is that it’s chronic. The good news is that there are quite a number of exciting new treatments in the works. This article is part of the APS resource library that I’m building up on the site for patients, as a patient who has lived with it for more than 20 years myself.

This post will focus on the latest research on Antiphospholipid Syndrome as of 2024, and I aim to update it as frequently as I can. The ultimate A to Z resource guide on Antiphospholipid Syndrome has also been released, so don’t forget to check that out for more in-depth information about APS.

*Disclaimer: This article is meant for educational purposes, and is based on my personal experiences as a patient. Whilst I have done my utmost to be meticulous in research, I am not a doctor, and nothing in this article should be substituted for medical advice. Please consult your own doctor before changing or adding any new treatment protocols. This post may also contain affiliate links. It will cost you nothing to click on them. I will get a small referral fee from purchases you make, which helps with the maintenance of this blog. Read our Privacy Policy page for more information. Thank you!

Last Updated:
• 7 June 2024: Discovery of 2 Missing Enzymes in People with Antiphospholipid Syndrome

Read Related Posts in the Antiphospholipid Syndrome Diagnosis Series:
• Antiphospholipid Syndrome Diagnosis: The A to Z Guide as a Patient
• Pregnancy, Miscarriage & Women’s Health in Antiphospholipid Syndrome
• The Lowdown on Medications & Antiphospholipid Syndrome (Warfarin, Enoxaparin, DOACs, NSAIDs & More)
• How Does Antiphospholipid Syndrome Affect The Body? (Beyond the Blood to Major Organs)
• The Annoying Thing About Living with Antiphospholipid Syndrome (My Personal Experiences)
• An Experience from Hell: Pulmonary Embolism, DVTs & Antiphospholipid Syndrome
• What it Feels Like to be Refused Treatment by a Hospital’s A&E / ER

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Personal Research is Important as a Patient

Before I begin, I just wanted to emphasise that it is important that you do your own research as a patient with Antiphospholipid Syndrome. This can feel like a colossal task in the beginning, with a long list of foods, drinks, medications and activities that you need to moderate. It took me a long time to figure out what works for me through trial and error, often unwittingly. But trust me, you will learn over time, and become more confident with living with this autoimmune disease. Knowledge is power, and doing your own research on Antiphospholipid Syndrome in relation to its impact on your personal life can also help to make you feel more empowered.

“Knowledge is power, and doing your own #research on #AntiphospholipidSyndrome in relation to its impact on your personal life can also help to make you feel more #empowered.” #ChronicIllness #APS
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There are also a few things you can do online to ensure that you don’t miss out on the latest research on Antiphospholipid Syndrome. I personally subscribe to Google Alerts for keywords related to: “Antiphospholipid Syndrome”, “Lupus”, “autoimmune disease”, “chronic illness” and the likes.

Another tool I use is Feedly, an RSS (Really Simple Syndication) feed, where I subscribe to specific websites and news to browse through on a daily basis. If you’re curious as to how an RSS feed looks like, this is the one for this website. You simply need to add the URL to Feedly, and everything published on my blog will be in your reader. The best part is that these tools are free to use, and you can add any other topic that you’re interested in as well!

Finally, I also rely quite a bit on Google Scholar to learn more about various aspects of Antiphospholipid Syndrome from a medical and scientific perspective. In fact, all of the latest research on Antiphospholipid Syndrome that you will read about in this post can be found on Google Scholar – so it is indeed possible to keep up with the research on your own, too! There are many websites on ‘regular’ Google search, but it’s important to note that not all of these sources are verified, whereas articles on Google Scholar are. If you do choose to do your own research via ‘regular’ Google, do ensure that the source is from an established organisation, such as the NHS or Cleveland Clinic.

A Breakdown of the Latest Research on Antiphospholipid Syndrome

Whilst there are quite a number of promising new research and clinical trials for Antiphospholipid Syndrome, it is still a rare disease that could use more public awareness and research funding. The American College of Rheumatology (ACR) holds an annual convergence that showcases the latest research and knowledge into all areas of rheumatology. Here are the new Antiphospholipid Syndrome findings that were presented at the ACR convergence in 2023, and I can’t wait to see what will be shared in the next one in November 2024!

“Check out the latest #research on #AntiphospholipidSyndrome, from diagnosis tools to proteins, NETs, DNA molecules and more.” #APS #AutoimmuneDisease #ChronicIllness
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Peptide Libraries for Diagnosing Antiphospholipid Syndrome

Let’s begin with exciting new advancements in the diagnosis stage of APS. The current tests available for the detection of autoantibodies that target prothrombin (aPT) are aPS/PT, and aPT-A assays. However, it has been difficult to standardise their detection in lab tests, due to variability in platforms and protocols.

One new diagnostic tool in the works is a novel ELISA assay, ProTS525A-Biot (aPT-Bio). In a study of 27 high-risk APS patients, the ProTS525A-Biot was able to identify 24 triple-positive APS patients. ProTS525A-Biot may also be useful in future for the detection of other prothrombotic conditions apart from APS, such as COVID-19 (Chinnaraj et al., 2021).

Another diagnostic tool in the works is based on peptide IIa‐8.0‐biot‐2x, which is able to interact with antiphospholipid antibodies (aPLs) to a much larger extent (Moghbel et al., 2022).

Research on B Cells & T Cells in Autoimmune Diseases

If you live with an autoimmune disease, chances are that you’ve heard of T cells and B cells, and might even have underwent a biologic infusion to try and eliminate them, as they often trigger autoimmune disease activity when they go awry. T cells and B cells are lymphocytes, which are a type of white blood cell. As per the National Human Genome Research Institute, B cells produce antibodies that target invading bacteria, viruses and toxins, whilst T cells destroy the body’s own cells that have become infected, or have turned cancerous.

There has been some fascinating research into T cells and B cells, although they are still in the preclinical stages. According to Taylor et al. (2023):

“One such therapy is redirecting T cells to selectively kill anti-β2GPI antibody-producing B cells using chimeric autoantigen-TCRs (CATCRs), allowing T cells to bind autoantigen-specific B-cell receptors (BCRs) and induce selective cell death. Other B-cell therapies include monoclonal antibodies to B-cell activating factor (BAFF), which has been shown to exist at higher levels in many types of autoimmune diseases, including APS.”

In brief, T cells and B cells go hand in hand in the body, and targeting one will affect the other for better or for worse. Within the thymus gland, B cells play an active role in ‘training’ T cells on which cells to attack, and which to leave alone.

According to Afzali et al. (2024) in this latest research paper:

“CD40-induced B cell antigens, which, besides AQP4, comprise additional potentially disease-relevant autoantigens such as Anxa2, App and Cpd. Autoantibodies to ANXA2 and APP are associated with antiphospholipid syndrome and cerebral amyloid angiopathy-related inflammation.”

Thus, perhaps future treatments for Antiphospholipid Syndrome might target B cells and T cells more specifically, by ‘switching off’ the bad stuff whilst leaving the good alone.

Disruption of Neutrophilic Involvement in Antiphospholipid Syndrome

According to Papayannopoulos (2018), “Neutrophils are the most abundant innate immune effector cells of the human immune system”, and come with antimicrobials on a broad spectrum. Neutrophil extracellular traps (NETs) are a combination of chromatin fibres, DNA and histones, and they play an important role in immobilising and killing invasive microorganisms, thereby protecting against infection.

However, NETS are also sources of autoantigens and immunostimulatory proteins, and can stimulate autoimmune diseases such as Lupus (SLE), vasculitis and psoriasis (Kaplan and Radic, 2012). Apart from that, NETs play a role in blood coagulation both through platelet and coagulation cascade activation, and can contribute to the formation of both arterial and venous blood clots (Kmeťová et al., 2023).

Clinical trials in Primary Antiphospholipid Syndrome patients with no comorbidities have also shown that these individuals had high levels of anti-NET antibodies, which can potentially trigger the complement cascade (Zuo et al., 2023). Another study found that APS patients with a high risk of thrombosis had more NETs and activated protein C resistance (Foret et al., 2022).

With NETs being drivers of thromboinflammation in APS, research into disruption of this pathway is underway. Two FDA-approved medications with antineutrophilic properties are being studied, as well as selective modulation of immune cell activity. This could potentially result in neutralisation of adhesive properties of cells, thus reducing thrombosis in both arterial and venous vascular beds (Taylor et al., 2023).

Beta-2-Glycoprotein I (β2GPI) & Future Therapeutic Research in Relation to APS

There are only three proteins in the body that are able to up and down regulate the complement and coagulation systems, namely: C-reactive protein (CRP), thrombomodulin and Beta-2-Glycoprotein I (β2GPI). β2GPI is a unique five domain protein, and exists in open (J-shaped), S-twisted, and closed (O-shaped) conformations (McDonnell et al., 2020), and according to Ağar et al. (2010):

“In contrast to the circular conformation, the open fishhook-like conformation of β2GPI has a profound effect on the aPTT. Therefore, we propose that the conformation of β2GPI in plasma is predominantly circular.”

Coagulation from β2GPI is dependent on the surrounding environment, and can have an anticoagulant, antiplatelet and procoagulant effect (McDonnell et al., 2020). β2GPI is also known to bind to phospholipids and DNA, where interactions with DNA further extend to NETs (which we touched on previously) (Kmeťová et al., 2023).

According to McDonnell et al. (2020):

“These actions of β2GPI can be influenced by aβ2GPI antibodies present in patients with APS and may be potential therapeutic targets. Assays to measure levels of antibodies to β2GPI and to DI show promise in improving diagnosis and risk stratification of patients with APS. A number of proposed therapeutic agents that target β2GPI/aβ2GPI interactions are in development.”

In basic terms, what this means is that β2GPI has implications in coagulation and Antiphospholipid Syndrome. Future therapies may target the blocking of these interactions, in order to reduce the cascade of thrombosis.

One of these new potential therapeutics is A1-A1, which is a peptide that targets the fifth domain of β2GPI, in order to prevent binding to cell surfaces. Another potential therapeutic is TIFI, a cytomegalovirus capsid peptide, which also targets the fifth domain of β2GPI, and might be able to inhibit the thrombotic effects of IgG antibodies.

1N11 is a monoclonal antibody that has also been shown to target ß2GP1 to decrease binding of antiphospholipid antibodies (aPLs) to proteins. Recombinant domain I molecule is also able to bind to aPLs, which in turn prevents their adverse effects. Researchers are still trying to understand the full role of β2GPI as well as Antiphospholipid Syndrome. So whilst these therapeutics sound exciting, it will probably still be many years before we see them in practice (McDonnell et al., 2020; Fierro et al., 2022).

Aptamers / Next-Generation Thrombin Inhibitor Consisting of DNA Molecules

Finally, let’s take a look at aptamers. Aptamers are single-stranded oligonucleotides (DNA or RNA molecules) that are capable of binding to proteins or other cellular targets with great specificity (Arbuthnot, 2015; Ni et al., 2011). They are small in size, non-immunogenic, and there are different kinds that show promise in a variety of immune related treatments – from antibiotic alternatives, to autoimmune diseases such as Sjögren’s disease, to suppression of tumour growth. The good news is that many of these therapeutic aptamers are in the mid to late stage of clinical trials, and might be ready within 5 – 10 years (Yasmeen et al., 2020).

In relation to Antiphospholipid Syndrome and its potential complications, a new DNA drug to fight blood clots has been discovered. Heparin is used as an anticoagulation drug in APS patients during emergencies, but up to 3% of patients who are on heparin for various medical reasons develop heparin-induced thrombocytopenia (HIT), which causes the blood to clot instead. HIT is a life-threatening complication where platelet counts drop, and the patient is at risk of thrombosis. The medications used to treat HIT – argatroban and bivalirudin – have no antidotes.

Recently it has been found that the anti-thrombin DNA aptamer, M08s-1, might act as a promising antidote for HIT. It also does not cross over into the placenta of pregnant women. According to Nagano et al. (2023):

“The dimerized M08s-1-based aptamers had about 100-fold increased binding affinity to human and mouse thrombin compared with the monomer counterparts.”

Discovery of 2 Missing Enzymes in People with Antiphospholipid Syndrome

According to NaveenKumar et al. (2024):

“Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.”

Goodwin from Michigan Medicine explains this unexpected research finding in simpler terms here. In brief, the enzymes CD39 and CD73 which normally work together to cool down inflammatory molecules known as adenosine triphosphate were not found in patients with APS. This results in instigation of cells like neutrophils and platelets that contribute to the blood coagulation cascade.

NaveenKumar et al. (2024) has also discovered that the receptors P2X7 and P2Y2, which play a role in platelets and neutrophils respectively, are key components in the inflammatory response from the accumulated adenosine triphosphate. Blocking these receptors on cells related to Antiphospholipid Syndrome returned them to a healthy state.

Research such as this matters so much even if there is little funding for research into Antiphospholipid Syndrome specifically. Every bit of knowledge helps medicine to advance as a whole.

Conclusion to the Latest Research on Antiphospholipid Syndrome

Currently the main form of APS management and treatment is with the use of blood thinning medications, which come their own sets of problems. So it’s interesting to see that the future direction of APS treatment delves quite a bit into more targeted therapies on a biological level.

I hope that this peek into the latest research on Antiphospholipid Syndrome has granted you some insight and hope into the possibilities of more effective APS diagnosis, prevention and treatments on the horizon. Perhaps some day, these fantastic researchers and doctors will find a cure as well. For now, take good care of yourself, and keep an eye out for the A – Z Antiphospholipid Syndrome guide to be released soon!

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References:

1. Afzali, A. M., Nirschl, L., Sie, C., Pfaller, M., Ulianov, O., Hassler, T., … & Korn, T. (2024). B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4. Nature, 627, 407-415. https://doi.org/10.1038/s41586-024-07079-8
2. Ağar, Ç., van Os, G. M., Mörgelin, M., Sprenger, R. R., Marquart, J. A., Urbanus, R. T., … & de Groot, P. G. (2010). β2-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood, The Journal of the American Society of Hematology, 116(8), 1336-1343. https://doi.org/10.1182/blood-2009-12-260976
3. Arbuthnot, P. (2015). Chapter 5 – Delivery of Antiviral Nucleic Acids with Nonviral Vectors. Gene Therapy for Viral Infections. 127-150. https://doi.org/10.1016/B978-0-12-410518-8.00005-3
4. Chinnaraj, M., Pengo, V., & Pozzi, N. (2021). A novel ELISA assay for the detection of anti-prothrombin antibodies in antiphospholipid syndrome patients at high risk of thrombosis. Frontiers in Immunology, 12, 741589. https://doi.org/10.3389/fimmu.2021.741589
5. Cleveland Clinic. (2022). Heparin-Induced Thrombocytopenia. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/diseases/24014-heparin-induced-thrombocytopenia
6. Fierro, J. J., Velásquez, M., Cadavid, A. P., & de Leeuw, K. (2022). Effects of anti‐beta 2‐glycoprotein 1 antibodies and its association with pregnancy‐related morbidity in antiphospholipid syndrome. American Journal of Reproductive Immunology, 87(1), e13509. https://doi.org/10.1111/aji.13509
7. Foret, T., Dufrost, V., Salomon du Mont, L., Costa, P., Lakomy, C., Lagrange, J., … & Wahl, D. (2022). A new pro-thrombotic mechanism of neutrophil extracellular traps in antiphospholipid syndrome: impact on activated protein C resistance. Rheumatology, 61(7), 2993-2998. https://doi.org/10.1093/rheumatology/keab853
8. Goodwin, V. (April 18, 2024). Helpful enzymes vanish in many patients with antiphospholipid syndrome. Michigan Medicine. Retrieved from: https://www.michiganmedicine.org/health-lab/helpful-enzymes-vanish-many-patients-antiphospholipid-syndrome
9. Hospital for Special Surgery. (2023). New Antiphospholipid Syndrome Research Findings Presented at ACR Convergence 2023. Hospital for Special Surgery. Retrieved from: https://news.hss.edu/new-antiphospholipid-syndrome-research-findings-presented-at-acr-convergence-2023/
10. Kaplan, M. J., & Radic, M. (2012). Neutrophil extracellular traps: double-edged swords of innate immunity. The Journal of Immunology, 189(6), 2689-2695. https://doi.org/10.4049/jimmunol.1201719
11. Kmeťová, K., Lonina, E., Yalavarthi, S., Levine, J. S., Hoy, C. K., Sarosh, C., … & Knight, J. S. (2023). Interaction of the antiphospholipid syndrome autoantigen beta-2 glycoprotein I with DNA and neutrophil extracellular traps. Clinical Immunology, 255, 109714. https://doi.org/10.1016/j.clim.2023.109714
12. McDonnell, T., Wincup, C., Buchholz, I., Pericleous, C., Giles, I., Ripoll, V., … & Rahman, A. (2020). The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS. Blood reviews, 39, 100610. https://doi.org/10.1016/j.blre.2019.100610
13. Moghbel, M., Roth, A., Baptista, D., Miteva, K., Burger, F., Montecucco, F., … & Brandt, K. J. (2022). Epitope of antiphospholipid antibodies retrieved from peptide microarray based on R39‐R43 of β2‐glycoprotein I. Research and Practice in Thrombosis and Haemostasis, 6(7), e12828. https://doi.org/10.1002/rth2.12828
14. Nagano, M., Kubota, K., Sakata, A., Nakamura, R., Yoshitomi, T., Wakui, K., & Yoshimoto, K. (2023). A neutralizable dimeric anti-thrombin aptamer with potent anticoagulant activity in mice. Molecular Therapy-Nucleic Acids, 33, 762-772. https://doi.org/10.1016/j.omtn.2023.07.038
15. National Human Genome Research Institute. (2024). Lymphocyte. National Human Genome Research Institute. Retrieved from: https://www.genome.gov/genetics-glossary/Lymphocyte
16. NaveenKumar, S. K., Tambralli, A., Fonseca, B. M., Yalavarthi, S., Liang, W., Hoy, C. K., Sarosh, C., Rysenga, C. E., Ranger, C. H., Vance, C. E., Madison, J. A., Orsi, F. A., Sood, S. L., Schaefer, J. K., Zuo, Y., & Knight, J. S. (2024). Low ectonucleotidase activity and increased neutrophil-platelet aggregates in patients with antiphospholipid syndrome. Blood, 143(12), 1193–1197. https://doi.org/10.1182/blood.2023022097
17. Ni, X., Castanares, M., Mukherjee, A., & Lupold, S. E. (2011). Nucleic acid aptamers: clinical applications and promising new horizons. Current medicinal chemistry, 18(27), 4206-4214. https://doi.org/10.2174/092986711797189600
18. Papayannopoulos, V. (2018). Neutrophil extracellular traps in immunity and disease. Nature Reviews Immunology, 18(2), 134-147. https://doi.org/10.1038/nri.2017.105
19. Taylor, A., Kumar, S., & Pozzi, N. (2023). Forecasting the Future of Antiphospholipid Syndrome: Prospects and Challenges. Missouri Medicine, 120(5), 359-366. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/37841574
20. Technical University of Munich (TUM). (2024). Possible trigger for autoimmune diseases discovered : B cells teach T cells which targets must not be attacked. ScienceDaily. Retrieved from: https://www.sciencedaily.com/releases/2024/02/240221160321.htm
21. University of Tokyo. (2023). A new DNA drug to fight blood clots. ScienceDaily. Retrieved from: https://www.sciencedaily.com/releases/2023/08/230821114401.htm
22. Yasmeen, F., Seo, H., Javaid, N., Kim, M. S., & Choi, S. (2020). Therapeutic interventions into innate immune diseases by means of aptamers. Pharmaceutics, 12(10), 955. https://doi.org/10.3390/pharmaceutics12100955
23. Zuo, Y., Navaz, S., Tsodikov, A., Kmetova, K., Kluge, L., Ambati, A., … & Branch, D. W. (2023). Anti–Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody–Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. Arthritis & Rheumatology, 75(8), 1407-1414. https://doi.org/10.1002/art.42489