Antiphospholipid syndrome
Antiphospholipid syndrome is an acquired autoimmune thrombophilia in which antiphospholipid antibodies cause recurrent venous and arterial thrombosis and pregnancy morbidity, paradoxically prolonging the aPTT in vitro while promoting clotting in vivo. Diagnosis requires a qualifying clinical event plus a laboratory antibody confirmed positive on two occasions at least 12 weeks apart, and thrombotic disease is treated with indefinite warfarin rather than a DOAC.
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What this article covers
- Overview
Definition: antiphospholipid syndrome (APS) is an acquired autoimmune clotting disorder in which circulating antiphospholipid antibodies cause recurrent venous, arterial, or small-vessel thrombosis and characteristic pregnancy morbidity.
- Epidemiology
Antibody prevalence versus disease: antiphospholipid antibodies occur in a meaningful fraction of the general population, but only a minority of antibody-positive individuals develop the clinical syndrome.
- Risk factors
Underlying SLE or another autoimmune disease: the strongest association for secondary APS; anti-double-stranded DNA or antiphospholipid antibodies predict an SLE flare in pregnancy.
- Pathophysiology
Antibody targets: antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta2-glycoprotein I) bind phospholipid-binding plasma proteins, chiefly beta2-glycoprotein I, on cell membranes and clotting-cascade components.
- Clinical features
Venous thromboembolism: deep vein thrombosis of the leg is the single most common manifestation, with pulmonary embolism as a frequent complication.
- Differential diagnosis
Thrombotic thrombocytopenic purpura: thrombocytopenia and microangiopathic hemolysis with schistocytes and severely reduced ADAMTS13 activity (below 10%), distinguishing it from antibody-driven…
- Diagnosis
Establish the diagnosis with the revised Sapporo (2006) classification criteria: definite APS requires at least one clinical criterion plus at least one laboratory criterion.
- Management
Acute venous or arterial thrombosis: begin LMWH (enoxaparin 1 mg/kg SC every 12 hours) or unfractionated heparin, overlapped with warfarin until the INR is therapeutic for at least 24 hours, then stop the heparin.
- Complications
Recurrent thrombosis: the dominant long-term risk, especially with triple-positive serology or inadequate anticoagulation intensity.
- Prognosis
Thrombosis-free survival depends on anticoagulation adherence and intensity: patients maintained on lifelong warfarin at the correct INR target have substantially lower recurrence rates than those undertreated or switched to a DOAC.
- Prevention
Confirm before treating: never diagnose or treat based on a single positive antibody result; repeat testing at 12 weeks or more, since transient positivity from infection or inflammation is common.
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