A 35-year-old woman with SLE has recurrent arterial and venous thromboses, three second-trimester pregnancy losses, and a prolonged aPTT that does not correct on mixing study. The diagnosis and pathogenic mechanism are:

• A Heparin-induced thrombocytopenia — IgG antibodies against PF4-heparin complexes activating platelets
• B Antiphospholipid syndrome — antiphospholipid antibodies activating endothelium and platelets, impairing natural anticoagulants ✓
• C Factor V Leiden — resistance to activated protein C
• D Prothrombin G20210A mutation — elevated prothrombin levels

Explanation

Antiphospholipid syndrome (APS) causes recurrent thromboses and pregnancy losses due to antibodies against beta2-glycoprotein I and cardiolipin. These antibodies paradoxically prolong aPTT in vitro (lupus anticoagulant) but cause thrombosis in vivo by activating endothelium and platelets and impairing natural anticoagulants. HIT involves PF4-heparin antibodies with thrombocytopenia; Factor V Leiden and prothrombin mutations are hereditary thrombophilias without autoantibodies.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.