APS 101 Series: Obstetric Antiphospholipid Syndrome

The APS 101 Series, written by Jacqueline Madison, MD, takes you through the ins and outs of APS, providing facts and key information to help you better understand the disorder. In this month’s edition, Dr. Madison discusses obstetric antiphospholipid syndrome, issues that can arise, and treatment strategies.

Obstetric Antiphospholipid Syndrome

In this blog series, I have talked a lot about thrombotic APS including different types of blood clots, how to figure out if you have a blood clot, and ways to treat and prevent blood clots. It is important that we also discuss obstetric (pregnancy-related) problems associated with APS.

For some patients, their APS is identified when they have difficulties with pregnancy, either becoming or staying pregnant. Others may already know they have APS, but need to learn about potential pregnancy issues as they approach pregnancy.

Potential pregnancy issues

So, what are the different issues that arise in APS pregnancies? The new 2023 ACR/EULAR APS classification criteria identify several problems in pregnancy known to be related to APS¹. While the criteria do not cover every possible scenario, they highlight the most common issues we see in our patients.

One reminder: these criteria are made for classification, which means defining APS for research purposes, not diagnosis. Diagnosis can only be done by your doctor.

These new criteria are different than the previous criteria, which I discussed in a blog post in December 2021, so now is a good time to review.

Early pregnancy losses

Sometimes APS is first identified when someone has recurrent early miscarriages and no other reason for them. Different terms are used for these early losses. In the APS criteria, they are defined as being either pre-fetal (under 10 weeks gestation) or early fetal (10 weeks through 15 weeks gestation). Multiple losses “count,” so to speak, towards a classification of APS if they are consecutive, or all in a row.

If there are healthy pregnancies in between miscarriages, that is a pattern less specific for APS. If early pregnancy losses are the first symptoms of APS, the issue is most likely to be identified by our colleagues in obstetrics and gynecology. If antiphospholipid antibodies are detected, we, rheumatologists specializing in APS, typically get the call to evaluate the situation.

Because there are unfortunately many other causes of early miscarriages, this pattern of problems is not as specific for APS as they are for severe preeclampsia or placental insufficiency, which I talk about below.

Later pregnancy loss without another cause

Unfortunately, sometimes APS is not identified until after a late pregnancy loss, which can be devastating. Testing after a case of late fetal death (defined in the APS criteria as 16 weeks or later) is sometimes how APS is identified. However, in the absence of preeclampsia or placental insufficiency, it is important to look carefully for other causes of the loss because there are a lot of other possible causes.

Severe preeclampsia or placental insufficiency

These types of problems are felt to be the most specific for APS, especially when they lead to delivery before 34 weeks gestation.

For our purposes, preeclampsia means that a pregnant patient has both high blood pressure (>140/90) and high protein in their urine. It is considered “severe” when there is one additional problem: even higher blood pressure (>160/110), new headache, change in vision, fluid in the lungs, liver problems, kidney dysfunction, or low platelets (<100).

Placental insufficiency means that the placenta, which provides oxygen and nutrients to the growing fetus, is not working normally. Placental insufficiency is called “severe” when there are signs that the fetus is not growing well based on their size (under the 10th percentile) combined with at least one other problem: abnormal fetal surveillance test (like a non-stress test), abnormal testing of blood flow to the baby (Doppler testing), severe growth restriction (less than the 3rd percentile), or not enough amniotic fluid (oligohydramnios).

Sometimes it can be difficult to diagnose a patient with obstetric APS if they have not also had blood clots. That’s because many of these obstetric problems are also seen in patients with difficult pregnancies for other reasons.

We feel most definite about the APS diagnosis when blood testing for antiphospholipid antibodies is strongly positive or other parts of the person’s history also point toward a diagnosis of APS. We have seen patients who had some of these obstetric problems years ago and then developed blood clots later in life. Only then, after putting the whole history together, did the medical team test for antiphospholipid antibodies.

Treatment strategies

There are treatment strategies to help patients achieve healthy (or at least healthier) pregnancies, so the first step is to identify obstetric APS. Our colleagues in obstetrics and gynecology often do an excellent job finding these at-risk patients, and when we work together, often with hematology also, we can diagnose obstetric APS and then come up with an individualized management plan².

In patients with antiphospholipid antibodies, but no history of obstetric or thrombotic problems, low-dose aspirin is often the recommended treatment. For other patients, we recommend a combination of low-dose aspirin and a prophylactic dose of low-molecular-weight heparin (Lovenox). If patients have a history of a blood clot, then the dose of low-molecular-weight heparin will likely be higher. We always work very closely with hematology and obstetrics when making these decisions. 

When patients need additional support, we sometimes recommend hydroxychloroquine, which is a lupus drug with a long track record of use during pregnancy. In addition to a diagnosis of lupus, other factors that point us toward hydroxychloroquine are very high antibody levels or ongoing difficulties despite aspirin and low-molecular-weight heparin.

Like for all patients with APS, we hope to increasingly personalize the treatment of obstetric APS, attacking underlying immune-mediated mechanisms. There is hope we will have new treatment options in the future.

For example, an ongoing trial is enrolling North American patients to test whether certolizumab (Cimzia) improves outcomes for obstetric APS. For pregnant individuals with APS and positive lupus anticoagulant testing, the trial is adding certolizumab to the usual treatments. Certolizumab inhibits an inflammatory molecule called TNF. It is commonly used for rheumatoid arthritis, especially during pregnancy where it is safer than alternative medications. More information can be found at ClinicalTrials.gov.

Pregnancy is a time of significant physiologic stress on the body, and it takes a team approach to diagnose and successfully treat this important and life-changing aspect of APS. We and others are working hard to improve outcomes even further.

References:

1. Barbhaiya M, Zuily S, Naden R, et al. The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria. Arthritis Rheumatol 2023;75(10):1687-702. doi: 10.1002/art.42624 [published Online First: 2023/08/28]

2. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol 2020;72(4):529-56. doi: 10.1002/art.41191 [published Online First: 2020/02/25]

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