A 60-year-old man presents with recurrent venous thromboembolism despite adequate anticoagulation with heparin and warfarin. Laboratory evaluation reveals resistance to activated protein C (APC resistance). Which genetic mutation is most likely responsible?

• A Antithrombin III deficiency
• B Factor V Leiden mutation ✓
• C Prothrombin G20210A mutation
• D Protein C deficiency

Explanation

Factor V Leiden (Arg506Gln) is the most common inherited thrombophilia, causing activated protein B resistance. The mutation removes the cleavage site on factor V where APC normally inactivates factor Va, leading to sustained thrombin generation. It is autosomal dominant and present in approximately 5% of Caucasians. Antithrombin deficiency, prothrombin mutation, and protein B deficiency are other inherited thrombophilias but do not cause APC resistance.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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