Hereditary thrombophilia / hypercoagulopathies
Protein C deficiency

Topic Completed: 1 June 2012

Revised: 7 January 2019, last major update June 2012

Copyright: (c) 2002-2016,, Inc.

PubMed Search: Protein C deficiency [title]

Page views in 2019: 231
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Cite this page: Parsons J. Protein C deficiency. website. Accessed June 7th, 2020.
Definition / general
  • Hereditary deficiencies occur in 0.14 - 0.5% of general population (the clinically significant incidence is much lower)
  • > 160 mutations exist, either type I (76%, usually quantitative) or type II (dysfunctional protein, normal protein levels)
  • Causes 1 - 11% of cases of venous thrombosis
  • These patients are also at risk for warfarin-induced skin necrosis if treated with warfarin and no heparin until warfarin levels are therapeutic; this paradoxical clotting is due to a faster fall in natural anticoagulant proteins than procoagulant proteins in these patients
  • Heterozygotes have levels 35 - 65% of normal
  • First thrombotic event occurs between ages 10 - 50 years
  • Only 30% have thromboembolism, increasing to 75% if coexisting factor V Leiden
  • Homozygotes (1 per 500 - 750K births) with severely decreased levels present as newborns with DIC and purpura fulminans neonatorum, leading to death unless anticoagulation and replacement therapy with fresh frozen plasma is started
  • Homozygous protein C deficiency can be cured with liver transplant; however, this is usually too risky so replacement is preferred treatment
  • Must exclude acquired causes of protein C deficiency
  • Acquired causes of low protein C levels:
    • Clot formation
    • Surgery
    • Liver disease
    • Warfarin (should be discontinued at least 10 days prior to testing) or Vitamin K antagonist therapy
    • DIC
    • Vitamin K deficiency
    • L-asparaginase therapy

  • Acquired causes of increased protein C (may mask protein C deficiency):
    • Ischemic heart disease
    • Pregnancy
    • Postmenopausal women
    • Hormone replacement therapy
    • Oral contraceptives
Clinical images

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Warfarin induced skin necrosis

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