There is a condition present in approximately one in five women with recurrent miscarriage.
It is fully treatable. The treatment is inexpensive. The evidence behind it is strong and consistent.
And a significant proportion of women who have it have never been tested for it.
It is called antiphospholipid syndrome (APS ) and if you have experienced recurrent pregnancy loss, this post could be one of the most important things you read.
WHAT IS ANTIPHOSPHOLIPID SYNDROME?
Antiphospholipid syndrome is an autoimmune condition in which the immune system produces antibodies called antiphospholipid antibodies that attack phospholipids, the fatty molecules that form the membranes of every cell in the body.
In most contexts the body tolerates this quietly. But in pregnancy, where a rich network of tiny blood vessels must develop rapidly to supply the growing placenta, the consequences of these antibodies become critical.
Antiphospholipid antibodies promote a prothrombotic state they make blood more likely to clot than normal. In the placental vessels, where blood flow must be smooth and uninterrupted to deliver oxygen and nutrients to the developing embryo, even microscopic clots can be catastrophic.
The result is impaired placental development, reduced blood supply to the embryo, and in many cases miscarriage.
APS is found in approximately 15-20% of women with recurrent miscarriage. It is one of the most common identifiable and treatable causes of recurrent pregnancy loss.
And yet it is routinely missed because the testing is incomplete, because a single negative result is taken as definitive, and because not all three antibodies are always checked.
THE THREE ANTIBODIES WHY ALL THREE MUST BE TESTED
This is the most critical point in this entire post. Please read it carefully.
Antiphospholipid syndrome is diagnosed based on the presence of antiphospholipid antibodies. But there are three separate antibodies that can cause APS and missing any one of them can result in a missed diagnosis.
The three antibodies are:
1. Lupus anticoagulant (LA)
Despite its name, lupus anticoagulant has nothing to do with lupus in most cases it is simply a historical naming convention. It is the most strongly associated of the three antibodies with miscarriage and thrombosis. It is detected through clotting time tests rather than a direct antibody measurement, which means it requires specific laboratory request and interpretation.
2. Anticardiolipin antibodies (aCL) IgG and IgM
These antibodies target cardiolipin, a phospholipid found in cell membranes. Both IgG and IgM subtypes must be tested IgG is more strongly associated with clinical events but IgM is also clinically significant.
3. Anti-beta-2-glycoprotein-I antibodies (anti-β2GPI) IgG and IgM
These antibodies target a protein that binds to phospholipids. They are the most specific marker for APS and are associated with both thrombosis and obstetric complications. Again, both IgG and IgM subtypes should be tested.
A woman can have a negative anticardiolipin result and a positive lupus anticoagulant. She can have negative lupus anticoagulant and positive anti-β2GPI. Each antibody can be present independently.
Testing only one or two of the three means a proportion of APS cases will be missed.
If you have been told your antiphospholipid test was negative ask which antibodies were tested. If the full panel was not run, request it.
THE DIAGNOSTIC CRITERIA WHY ONE POSITIVE TEST IS NOT ENOUGH
APS is diagnosed when both clinical criteria and laboratory criteria are met.
Clinical criteria include one or more of the following:
•One or more unexplained deaths of a morphologically normal foetus at or beyond 10 weeks
•One or more premature births before 34 weeks due to placental insufficiency or severe preeclampsia
•Three or more unexplained consecutive miscarriages before 10 weeks
Laboratory criteria require:
• Positive antiphospholipid antibody on at least two separate occasions
At least 12 weeks apart
This second point is critical. A single positive test is not sufficient for diagnosis. Antiphospholipid antibodies can be transiently positive following infection, illness, or other acute events. A persistently positive result on repeat testing is required to confirm the diagnosis.
This means that if your first antiphospholipid test is positive, a repeat test 12 weeks later is essential before a diagnosis can be confirmed and before treatment can be formally initiated.
Conversely, if you have had only one test and it was negative, it is worth repeating in a different clinical context at a different time, in a different laboratory, ensuring all three antibody types are included.
HOW APS CAUSES MISCARRIAGE : THE MECHANISMS
Understanding how APS causes pregnancy loss helps explain why the treatment works.
The primary mechanism is thrombosis, the formation of small clots in the developing placental vasculature. The placenta is a highly vascular organ that begins developing in the first weeks of pregnancy. It relies on an intricate network of maternal blood vessels remodelling to allow adequate blood flow to the foetus. Antiphospholipid antibodies interfere with this remodelling and promote clot formation in these vessels, impairing placental blood supply.
But thrombosis is not the only mechanism. Research has identified direct effects of antiphospholipid antibodies on:
Trophoblast cells, the cells that form the placenta impairing their invasion into the uterine wall
•Complement activation, triggering an inflammatory cascade at the placental interface
• Endothelial cell function, damaging the lining of blood vessels directly
•Annexin V, a protein that normally forms a protective anticoagulant shield over placental cells; antiphospholipid antibodies displace this shield
This is why early miscarriages occur in APS not just the later losses that were historically associated with the condition. The mechanisms of early placental damage and direct embryotoxicity are now well established.
WHO SHOULD BE TESTED?
Every woman with recurrent miscarriage should be tested for the full antiphospholipid antibody panel.
But testing is also warranted in women with:
• A single late first trimester or second trimester loss (after 10 weeks)
•A history of severe preeclampsia or placental insufficiency
• Unexplained infertility or recurrent implantation failure in IVF
•A personal history of deep vein thrombosis or pulmonary embolism
• A personal or family history of autoimmune conditions lupus, rheumatoid arthritis, Sjögren's syndrome
• Unexplained thrombocytopenia (low platelet count)
• Livedo reticularis (a mottled, net-like skin pattern)
You do not need to have had three miscarriages to warrant this investigation. A single second trimester loss or a pattern of IVF implantation failure in the presence of good quality embryos is sufficient clinical reason.
THE TREATMENT: WHAT WORKS AND WHY
This is where the story becomes genuinely hopeful.
APS is one of the most treatable causes of recurrent miscarriage. The standard treatment protocol, low-dose aspirin combined with low molecular weight heparin has been shown in multiple randomised controlled trials to significantly improve live birth rates in women with APS and recurrent pregnancy loss.
Low-dose aspirin (75-100 mg daily) inhibits platelet aggregation and reduces the prothrombotic effects of antiphospholipid antibodies. It is typically started before conception either when trying to conceive or at a positive pregnancy test and continued through pregnancy.
Low molecular weight heparin (LMWH, such as enoxaparin) is an anticoagulant injected subcutaneously under the skin once daily. It is started at a positive pregnancy test and continued through pregnancy, typically until 34-36 weeks. Heparin does not cross the placenta and is safe for the developing baby.
The combination of aspirin and LMWH has been shown to increase live birth rates in women with APS and recurrent miscarriage from approximately 10-20% (without treatment) to 70-80% (with treatment).
That is not a marginal improvement. That is a transformative one.
Hydroxychloroquine, an antimalarial medication with well-established anti-inflammatory and immunomodulatory effects is increasingly used as an adjunct treatment in APS, particularly in women who do not respond fully to aspirin and heparin alone. It has a strong safety profile in pregnancy and is used routinely in lupus pregnancies.
WHAT TO EXPECT IN A TREATED PREGNANCY
If you are diagnosed with APS and become pregnant, your pregnancy will be managed as high risk not because the outlook is poor, but because careful monitoring significantly improves outcomes.
You can expect:
° Regular ultrasound surveillance for foetal growth and placental blood flow
° Uterine artery Doppler assessment to monitor placental vascular resistance
°Close monitoring for signs of preeclampsia
°Continued aspirin and LMWH throughout pregnancy
° Planned delivery timing based on placental function
Many women with APS go on to have healthy pregnancies and healthy babies with appropriate treatment and monitoring. The diagnosis is not a barrier to a successful pregnancy. It is, in most cases, the explanation that finally makes treatment possible.
QUESTIONS TO ASK YOUR DOCTOR
If you suspect APS or have not yet been fully tested, here is what to say:
"I would like the full antiphospholipid antibody panel including lupus anticoagulant, anticardiolipin antibodies IgG and IgM, and anti-beta-2-glycoprotein-I antibodies IgG and IgM. I understand that all three antibodies need to be tested and that a positive result needs to be confirmed on repeat testing 12 weeks later."
If you have already had one positive test:
"My antiphospholipid antibody came back positive. I understand that a repeat test 12 weeks later is required to confirm the diagnosis. Can we arrange this and discuss treatment options for my next pregnancy?"
If you have been told your test was negative but only one antibody was checked:
"I understand that APS requires testing of three separate antibodies, lupus anticoagulant, anticardiolipin, and anti-beta-2-glycoprotein-I. Can you confirm which were included in my panel and arrange testing for any that were not?"
THE LAB INTERPRETATION GUIDE
The inflammatory and immune markers section of the Lab Interpretation Guide for Fertility Health covers the key markers relevant to antiphospholipid syndrome and the broader immune picture in fertility and miscarriage including hsCRP, fibrinogen, and the thyroid autoimmunity markers that frequently coexist with APS.
If you are navigating recurrent miscarriage and want to understand your complete picture this guide was written for you.
→ Get the Lab Interpretation Guide here — $47
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A FINAL WORD
Antiphospholipid syndrome is present in one in five women with recurrent miscarriage.
It is treatable. The treatment is evidence-based. The outcomes with treatment are genuinely good.
And it is missed every day, in clinics around the world because the testing is incomplete, because one negative result is taken as definitive, and because women are not told what questions to ask.
You now know what to ask.
The information in this post is for educational purposes only and does not constitute medical advice.
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