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Updated: Jan 1 2022

Protein C/S Deficiency

  • 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
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