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