A 32-year-old woman is started on warfarin for deep vein thrombosis. On the third day of therapy she develops painful, necrotic skin lesions over her breasts and buttocks. The mechanism responsible for this complication is:

• A Direct toxic effect of warfarin on dermal capillary endothelium
• B Transient hypercoagulability from rapid fall of protein C before factors II, IX and X decline ✓
• C Type III hypersensitivity reaction to warfarin metabolites deposited in subcutaneous fat
• D Vitamin K excess causing microvascular platelet plugging

Explanation

Protein C has the shortest half-life among vitamin K dependent factors (about 6 hours). When warfarin is started without bridging heparin, anticoagulant protein C falls before procoagulant factors II, IX and X, producing a transient prothrombotic state that occludes microvessels in adipose-rich areas such as breast and buttock. Treatment is heparin bridging and vitamin K. Hypersensitivity and direct endothelial toxicity are not mechanisms of this classic entity.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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