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Pregnancy, Miscarriage & Women’s Health in Antiphospholipid Syndrome

Pregnancy, Miscarriage & Women's Health in Antiphospholipid Syndrome

This post is part of the Antiphospholipid Syndrome (APS) resource library that I’m building up on my site for patients, as a patient who’s lived with it for more than two decades myself. This article in particular will focus on all things related to the female sex and women’s health in Antiphospholipid Syndrome. It will cover topics such as pregnancy, miscarriage, menstruation, menopause, risk factors, birth control and other general knowledge.

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. The comprehensive A – Z Antiphospholipid Syndrome guide is taking me longer to complete but will be out soon, so keep an eye out for that!

*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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Pregnancy, Miscarriage and Women’s Health in Antiphospholipid Syndrome

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 where women first experienced a stroke, patients with comorbidities, and more (Dabit et al., 2021).

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APS - Women’s Health in Antiphospholipid Syndrome

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 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.

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.

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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From Birth to Menopause - The Life of a Female with Antiphospholipid Syndrome

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, unfractioned 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.

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Pregnancy Complications in Antiphospholipid Syndrome and Other Must Knows - Women’s Health and APS

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).

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 (ACA) 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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The Problems of Being a Female with Antiphospholipid Syndrome

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.

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.

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!

If you liked this article, sign up for our mailing list so you don’t miss out on our latest posts! You will also receive an e-book full of uplifting messages, quotes and illustrations, as a token of appreciation!

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Pregnancy, Miscarriage and Women’s Health in Antiphospholipid Syndrome

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