Protein C / Protein S anticoagulant pathway

Topic Completed: 1 June 2012

Revised: 4 January 2019, last major update June 2012

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

PubMed Search: Anticoagulant pathway [title]

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Cite this page: Parsons J. Protein C / Protein S anticoagulant pathway. website. Accessed July 13th, 2020.
Definition / general
  • Pathway is a physiologic anticoagulant system to limit blood clot formation (i.e. fibrinogen to fibrin conversion) to site of vessel injury
  • Major anticoagulant systems are protein C and protein S, antithrombin and tissue factor pathway inhibitor (TFPI, see extrinsic pathway)
  • Protein C and S: Vitamin K dependent anticoagulant proteins produced mainly in liver ("C" because was third peak to elute from a diethylaminoethyl affinity column and "S" because it was discovered in Seattle, WA)
  • Activation:
    • Endothelial cell protein C receptor binds thrombin-thrombomodulin complex, which activates protein C, which binds to free protein S on endothelial or platelet phospholipids surfaces
    • This protein C / protein S complex degrades factors Va and VIIIa, which reduces fibrin formation
    • Activated protein C also indirectly promotes fibrinolysis
    • 60 - 70% of protein S is bound to and inactivated by C4b binding protein, an acute phase reactant
  • Clinical note:
    • Since C4b increases during pregnancy, the protein S level will routinely fall below the normal non-pregnant range
    • Protein C has the shortest half life of the vitamin K dependent proteins
      • When placed on warfarin the patient loses the anticoagulant properties of protein C much more quickly than the pro-coagulation effects of factor VII, II, IX and X
      • This leads to warfarin necrosis which can be prevented by bridging with heparin
Diagrams / tables

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Protein C / S anticoagulant pathway

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