Coagulation - Protein C / Protein S anticoagulant pathway

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Coagulation

General

Protein C / Protein S anticoagulant pathway

Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 9 June 2012, last major update June 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● 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
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Protein C / Protein S anticoagulant pathway

Additional references
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● Arch Pathol Lab Med 2002;126:1337, Goodnight & Hathaway (Eds) (2000). Disorders of hemostasis & thrombosis: A clinical guide: McGraw-Hill

End of Coagulation > General > Protein C / Protein S anticoagulant pathway

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