Antiphospholipid syndrome (APLS, also called APS) is an autoimmune disorder in which the immune system produces antibodies that make blood clot too easily. These abnormal clots can form in veins or arteries anywhere in the body, leading to serious complications like deep vein thrombosis, stroke, and recurrent pregnancy loss. About 10 in every 100,000 people in the U.S. have the condition, and roughly 83% of them are women.
How APLS Causes Blood Clots
In a healthy immune system, antibodies target foreign invaders like bacteria and viruses. In APLS, the immune system mistakenly produces antibodies that attack certain proteins on the surface of blood vessel walls and blood cells. These antibodies aren’t just passive markers floating in the bloodstream. They actively drive clot formation through a process researchers describe as a “two-hit” model: the antibodies first damage the lining of blood vessels, then amplify the clotting response at that injury site.
Several things go wrong at the cellular level. The antibodies reduce the body’s production of nitric oxide, a molecule that normally keeps blood vessels relaxed and open. Without enough of it, vessels become stiff and prone to inflammation. At the same time, the antibodies ramp up production of tissue factor, a protein that kickstarts the clotting cascade, on the surface of immune cells and blood vessel walls. They also disrupt the energy-producing machinery inside certain white blood cells, generating harmful reactive oxygen molecules that cause further damage. On top of all this, the antibodies activate the complement system (a branch of immune defense) and interfere with the body’s ability to break down clots once they form.
Common Symptoms and Where Clots Form
APLS can affect virtually any organ, but some patterns are far more common than others. Venous blood clots, particularly deep vein thrombosis in the legs and pulmonary embolism in the lungs, are the most frequent vascular events. On the arterial side, stroke and transient ischemic attacks (mini-strokes) are the hallmark complications, even in younger adults who have no traditional risk factors for cardiovascular disease.
Beyond major clots, APLS can cause subtler problems. Many people develop livedo reticularis, a net-like purplish discoloration of the skin caused by sluggish blood flow in small vessels. Low platelet counts are also common, which can seem paradoxical in a condition defined by excessive clotting. Heart valve abnormalities, kidney damage from tiny clots in the filtering units, and cognitive difficulties from reduced blood flow to the brain are additional features that can develop over time.
The Link to Lupus and Other Conditions
APLS can occur on its own (primary APLS) or alongside another autoimmune disease, most commonly systemic lupus erythematosus (SLE). Between 20% and 40% of people with lupus carry antiphospholipid antibodies, and of those, 50% to 70% will eventually develop full APLS over the following two decades. In one large study of 554 lupus patients, about 20% had definitive APLS while another 45% tested positive for the antibodies without yet showing clinical signs of the syndrome. This overlap means that people diagnosed with lupus are routinely screened for these antibodies.
Pregnancy Complications
APLS is one of the leading treatable causes of recurrent pregnancy loss. The antibodies can damage the placenta’s blood supply, leading to miscarriage (especially after the 10th week of pregnancy), preterm birth, dangerously low amniotic fluid, poor fetal growth, preeclampsia, and HELLP syndrome, a serious condition involving liver and blood abnormalities.
Treatment during pregnancy typically involves a combination of low-dose aspirin and a blood-thinning injection. A meta-analysis found that this combination produced a significantly higher live birth rate than aspirin alone. For women who have a high-risk antibody profile but no prior clots or pregnancy losses, low-dose aspirin (75 to 100 mg daily) during pregnancy is generally recommended as a preventive step. If complications recur despite standard treatment, doctors may adjust the blood thinner dose or add other medications during the first trimester.
How APLS Is Diagnosed
Diagnosing APLS requires both a qualifying clinical event (a confirmed blood clot or specific pregnancy complication) and laboratory evidence of antiphospholipid antibodies. Three blood tests are used: the lupus anticoagulant test, anticardiolipin antibody test, and anti-beta-2 glycoprotein I antibody test. At least one of these must come back positive on two separate occasions, at least 12 weeks apart. That waiting period is critical because infections, medications, and other temporary conditions can cause a one-time positive result that doesn’t reflect true APLS.
The 2023 classification criteria from the American College of Rheumatology and EULAR introduced a weighted scoring system across six clinical categories: large-vein clots, arterial clots, small-vessel damage, obstetric complications, heart valve disease, and a laboratory domain. Each category assigns points based on severity and certainty, and a minimum combined score is needed for classification. The antibody test must be positive within three years of the clinical event to count. This scoring approach helps distinguish people with clear-cut APLS from those with borderline or uncertain findings.
Long-Term Treatment
For people who have had a blood clot, the cornerstone of APLS treatment is long-term anticoagulation with warfarin, a vitamin K antagonist that slows the clotting process. Unlike some other clotting disorders, APLS does not respond well to the newer direct oral anticoagulants (sometimes called blood thinners like rivaroxaban or apixaban). Clinical trials showed higher rates of recurrent clots with these newer drugs in APLS patients, so European guidelines specifically recommend against them for this condition.
For people who test positive for antiphospholipid antibodies but have never had a clot or pregnancy complication, the approach is more conservative. Low-dose aspirin (75 to 100 mg daily) is recommended for those with a high-risk antibody profile, particularly if they also have traditional cardiovascular risk factors like high blood pressure, smoking, or high cholesterol. Managing those conventional risk factors is equally important, since they can act as the “first hit” that sets the stage for a clot.
Catastrophic Antiphospholipid Syndrome
In rare cases, APLS can escalate into a life-threatening emergency called catastrophic antiphospholipid syndrome (CAPS). This involves widespread clotting across multiple organs simultaneously, often within days, leading to rapid organ failure. The kidneys, lungs, brain, heart, and liver are the most commonly affected. CAPS historically carried a mortality rate above 50%, though aggressive treatment strategies have brought that down to roughly 33%.
CAPS requires intensive hospital care combining multiple therapies at once: anticoagulation, high-dose steroids to suppress the immune response, plasma exchange to physically remove the harmful antibodies from the blood, and sometimes intravenous immunoglobulins. The rarity of CAPS (it accounts for less than 1% of all APLS cases) means it can be difficult to recognize quickly, which is part of what makes it so dangerous. Infections, surgery, and stopping anticoagulant medication are among the known triggers.