Snapshot A 40-year-old woman is bridged from heparin to warfarin for a recent provoked DVT. Soon after receiving warfarin, she develops dark lesions on her arms. They are large, dark, and necrotic. Warfarin is stopped and vitamin K and heparin are administered. Suspicious, her physician orders a specific assay that measures the activity of protein C. Overview Introduction Hypercoagulable state/thrombophilia caused by deficiency in protein C or S Genetics protein C deficiency - autosomal dominant protein S deficiency - autosomal dominant (much less common) Pathogenesis review of anticoagulation pathway protein C (with cofactor protein S) inactivates factors V and VIII remember, both are vitamin K-dependent both are synthesized in the liver deficiency of either protein C or S → active factors V and VIII thrombosis Mnemonics skin or subcutaneous necrosis after administration of warfarin remember, warfarin affects protein C and S first protein C deficiency is more common than protein S deficiency “protein C Cancels Coagulation” Presentation Symptoms of thrombosis after warfarin initiation skin and subcutaneous necrosis DVT or PE at a young age increased risk of DIC Evaluation Protein C or S functional assay (preferred) ↓ protein C or S activity levels Genetic testing not routinely done Differential Diagnosis Factor V Leiden mutation Antithrombin deficiency Antiphospholipid syndrome HIT Treatment For thrombosis protein C concentrate anticoagulate with heparin For warfarin-induced necrosis stop warfarin administer IV vitamin K administer heparin Prognosis, Prevention, and Complications Prognosis risk of thrombosis risk of warfarin-induced skin necrosis Prevention avoid warfarin avoid conditions that increase risk of thrombosis Complications miscarriage