A 35-year-old woman with systemic lupus erythematosus presents with recurrent miscarriages and a new deep vein thrombosis. Laboratory evaluation shows prolonged aPTT that does not correct on mixing study. Lupus anticoagulant is positive. Despite the prolonged aPTT in vitro, why is this patient thrombotic rather than bleeding?

• A Lupus anticoagulant directly activates platelets
• B Lupus anticoagulant inhibits tissue factor pathway inhibitor (TFPI)
• C The aPTT prolongation reflects factor VIII deficiency, but platelet activation causes thrombosis
• D Antiphospholipid antibodies bind endothelial cell annexin V, exposing procoagulant phospholipids in vivo ✓

Explanation

Antiphospholipid antibodies (including lupus anticoagulant) target phospholipid-binding proteins such as beta-2 glycoprotein I and annexin V on endothelial cells and trophoblasts. Displacement of annexin V exposes procoagulant phospholipids, promoting thrombosis in vivo. The in vitro aPTT prolongation is a laboratory artifact that does not reflect the in vivo hypercoagulable state.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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