Snapshot A newborn baby girl with no birth complications develops red purpuric lesions on the buttocks, elbows, and heels. She is lethargic and does not respond to soothing ointments. A pediatric dermatologist is consulted. By the time, the specialist sees the newborn, black eschars have formed on the pressure points. She is diagnosed with purpura fulminans and dies shortly after. Introduction Hypercoagulable state/thrombophilia caused by deficiency in protein C or S Genetics inherited protein C deficiency - autosomal recessive protein S deficiency – autosomal dominant (much less common) acquired decreased synthesis vitamin K antagonist administration severe liver disease with synthetic dysfunction 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 In severe cases purpura fulminans in newborns red purpuric lesions at pressure points progresses to painful black eschars Evaluation Protein C or S functional assay (preferred) ↓ protein C or S activity levels Plasma protein C or S antigen levels ↓ protein C or S antigen 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 administer protein C concentrate or fresh frozen plasma Prognosis, Prevention, and Complications Prognosis severe disease associated with neonatal mortality risk of warfarin-induced skin necrosis Prevention avoid warfarin avoid conditions that increase risk of thrombosis OCPs Complications miscarriage thrombosis neonatal purpura fulminans