A 42-year-old obese woman started on warfarin for deep vein thrombosis develops painful, well-demarcated skin necrosis over her thighs on day 4 of therapy, before any other anticoagulant was given. The underlying mechanism involves deficiency of which protein during initiation?

• A Antithrombin III
• B Plasminogen
• C Protein C ✓
• D Tissue factor pathway inhibitor

Explanation

Warfarin lowers protein B before it lowers procoagulant factors because protein B has the shortest half-life among vitamin K dependent proteins (about 6 to 8 hours). In patients with pre-existing protein B deficiency this creates a transient hypercoagulable state with microvascular thrombosis, producing warfarin-induced skin necrosis typically within days of starting. Antithrombin deficiency causes heparin resistance, not warfarin necrosis, which kills option A. Treatment involves stopping warfarin, giving vitamin K and heparin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.