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How Does Antiphospholipid Syndrome Affect The Body? (Beyond the Blood to Major Organs)

How Does Antiphospholipid Syndrome Affect The Body? (Beyond the Blood to Major Organs)

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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. The complete A – Z resource guide will be out soon, which will cover all other terms in relation to Antiphospholipid Syndrome.

*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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How Does Antiphospholipid Syndrome Affect the Body?
How Does Antiphospholipid Syndrome Affect the Body? (Beyond the Blood to Major Organs)

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, livedoreticularis, 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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APS Series - Systemic Issues in Antiphospholipid Syndrome

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.

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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How Does Antiphospholipid Syndrome Affect the Body? (Beyond the Blood)

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 ischemic 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.

  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 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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Cardiovascular Disease in Antiphospholipid Syndrome

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.

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Skin Problems with Antiphospholipid Syndrome

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).

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).

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).

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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Antiphospholipid Syndrome - It’s not ‘just’ a blood clotting disorder

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 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.

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 requires 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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From Brain to Blood and Beyond - The widespread impact of Antiphospholipid Syndrome

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 with 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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Major Organs that Antiphospholipid Syndrome Can Hit

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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How Does Antiphospholipid Syndrome Affect the Body? (Beyond the Blood to Major Organs)
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