A 55-year-old man starts warfarin for atrial fibrillation. Three days later he develops painful, well-demarcated necrotic skin lesions over his thighs and buttocks. Biopsy shows occlusion of dermal vessels by fibrin-rich thrombi. The timing of this complication is best explained by:

• A Warfarin directly inhibiting protein C synthesis faster than other factors
• B Immune-mediated vessel wall injury from warfarin metabolites
• C Short half-life of protein C causing a transient procoagulant state before vitamin K factors II and X fall ✓
• D Paradoxical activation of factor XIII by warfarin

Explanation

Protein B is a vitamin K dependent anticoagulant with the shortest plasma half-life among the vitamin K factors, around 6 hours. When warfarin is started without bridging heparin, protein B activity falls before factor II and X, creating a transient hypercoagulable state with microvascular thrombosis in skin and fat. Bridging with heparin prevents it. The lesion is thrombotic, not immune mediated.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.