Antiphospholipid syndrome (APS) is not directly inherited in the way conditions like sickle cell disease or cystic fibrosis are passed from parent to child. It does, however, have a genetic component. APS is a complex autoimmune condition where genetic predisposition combines with environmental triggers to produce the disease, meaning your genes can raise your risk without guaranteeing you’ll develop it.
Genetic Predisposition, Not Direct Inheritance
APS does not follow a simple inheritance pattern where one or two genes from a parent cause the condition. Instead, the genetic background is multifactorial, involving variations across many genes that each contribute a small amount of risk. This is typical of autoimmune diseases: no single gene is responsible, and having a family member with APS does not mean you will develop it yourself.
What researchers have identified are specific immune system gene variants that make a person more likely to produce antiphospholipid antibodies, the rogue proteins at the heart of APS. Certain variants in the HLA system (a group of genes that help your immune system distinguish your own cells from invaders) are consistently linked to higher antibody production. The variants HLA-DR4, HLA-DR7, and HLA-DQB1*0302 appear across different populations and in both primary APS and APS that develops alongside lupus. Importantly, these gene variants increase the likelihood of producing the problematic antibodies regardless of whether a person has any other autoimmune disease.
Primary APS (occurring on its own) and secondary APS (occurring alongside lupus or another autoimmune condition) also appear to have distinct genetic profiles. Research has found differences in genes related to mitochondrial function, oxidative stress, and inflammatory signaling between the two forms. This suggests that while they share some genetic ground, the specific constellation of gene variants may influence which form a person develops.
Genes Alone Don’t Cause APS
Even with a genetic predisposition, APS typically requires an environmental trigger to develop. Researchers describe this through a “two-hit” model. The first hit is some form of injury or activation of the blood vessel lining. The second hit amplifies the process, pushing the body toward abnormal clot formation.
Known triggers include:
- Infections: Viral infections are particularly associated with the production of antiphospholipid antibodies. Hepatitis C, HIV, COVID-19, Epstein-Barr virus, and several bacterial infections have all been linked to antibody formation.
- Medications: Certain drugs, including some used for heart rhythm problems and seizures, can trigger antibody production in susceptible people.
- Smoking: Tobacco use damages blood vessel linings and increases clotting tendencies, particularly in people who already carry antiphospholipid antibodies.
- Surgery and immobility: Surgical procedures are among the most common triggers for the severe, rapidly progressing form of APS known as catastrophic APS.
This explains why many people carry the genetic variants associated with APS but never develop the syndrome. Without the right environmental circumstances, the genetic predisposition stays silent.
What Happens During Pregnancy
One question that comes up frequently is whether a mother with APS can pass the condition to her baby. About 30% of children born to mothers with antiphospholipid antibodies do acquire these antibodies through the placenta during pregnancy. However, this is passive transfer, not genetic inheritance. The antibodies are the mother’s, temporarily circulating in the newborn’s blood, and they clear on their own as the baby’s system matures. Thrombosis (blood clotting) in these newborns is extremely rare, in part because placental passage appears to filter or limit the amount of antibody that reaches the baby.
There are rare documented cases of newborns producing their own antiphospholipid antibodies independently of any maternal transfer. In at least one case, a neonate had antiphospholipid antibodies in their blood that were absent from both cord blood and maternal serum, pointing to genuinely new antibody production. That infant also carried a separate inherited clotting gene variant (factor V Leiden), which likely compounded the risk. These cases are exceptional and don’t represent a typical pattern of hereditary transmission.
How Common APS Actually Is
APS affects roughly 10 per 100,000 people in the United States, based on 2019 prevalence data. It is far more common in women: the annual incidence rate for women is about 4.5 per 100,000, compared to roughly 0.9 per 100,000 for men. The most common form is thrombotic APS, involving abnormal blood clots, with a prevalence of about 5.4 per 100,000. Among women specifically, obstetric APS (causing pregnancy complications like recurrent miscarriage) affects about 3.7 per 100,000.
These numbers make APS relatively uncommon in the general population, which is worth keeping in mind if you have a family member with the condition and are concerned about your own risk. Having a relative with APS may mean you share some of the predisposing gene variants, but the overall likelihood of developing the full syndrome remains low.
What a Family History Means for You
If a close family member has APS, you may carry some of the same immune system gene variants that raise susceptibility. This does not mean you will develop APS, and there is no routine genetic test that predicts whether someone will go on to have the condition. The gene variants identified so far increase risk modestly and are common enough in the general population that most carriers never develop problems.
What a family history does warrant is awareness. Knowing that autoimmune conditions cluster in families can be useful context if you ever experience unexplained blood clots, recurrent pregnancy losses, or other symptoms that might prompt a clinician to test for antiphospholipid antibodies. The blood tests themselves are straightforward: they look for specific antibodies (anticardiolipin, lupus anticoagulant, and anti-beta-2 glycoprotein I) and need to be positive on at least two occasions, spaced at least 12 weeks apart, to be considered meaningful.
The 2023 classification criteria from the American College of Rheumatology and EULAR use a weighted scoring system that considers both the type of antibody findings and the clinical events a person has experienced, such as blood clots or pregnancy complications. A positive antibody test alone, without any clinical events, does not meet the threshold for an APS diagnosis.