antiphospholipid

Antiphospholipid refers to a group of autoimmune responses directed against phospholipid-binding proteins. The most clinically relevant manifestations arise when antiphospholipid antibodies persistently target proteins such as lupus anticoagulant, anticardiolipin antibodies, and anti-beta2 glycoprotein I. When these antibodies are present with clinical events, the condition is called antiphospholipid syndrome (APS). APS can be primary, occurring without another autoimmune disease, or secondary, most often in association with systemic lupus erythematosus or other autoimmune conditions. Antibodies may also be detected in healthy individuals, infections, or certain drugs, but a diagnosis of APS requires both laboratory positivity on two occasions at least 12 weeks apart and a compatible clinical history.

The pathogenic mechanism is thought to involve immune-mediated activation of endothelial cells, platelets, and coagulation pathways, creating a prothrombotic state. Paradoxically, some antibodies can prolong certain clotting tests in vitro, yet promote clotting in vivo. The clinical spectrum includes venous or arterial thrombosis and obstetric complications.

Clinical features commonly include thrombosis in veins (deep vein thrombosis, pulmonary embolism) or arteries (stroke, myocardial infarction), as well as pregnancy morbidity such as recurrent miscarriages, fetal death, or placental insufficiency. Additional features may include thrombocytopenia, livedo reticularis, or valve abnormalities.

Diagnosis relies on the Sydney criteria: a history of vascular thrombosis or pregnancy morbidity plus persistent laboratory positivity for lupus anticoagulant, anticardiolipin antibodies, or anti-beta2 glycoprotein I antibodies, confirmed on two occasions at least 12 weeks apart.

Management focuses on preventing thrombosis and optimizing pregnancy outcomes. Anticoagulation is standard after a thrombotic event (usually vitamin K antagonists with target INR around 2-3 for venous events; higher targets or adjunctive therapies may be used for arterial events). In pregnancy, low-dose aspirin combined with heparin improves live birth rates. For asymptomatic individuals with antibodies but no clinical events, monitoring and risk reduction are advised, with treatment tailored to overall risk. DOACs are generally avoided in high-risk APS.