Regulation of coagulation by protein S.

Abstract

PURPOSE OF REVIEW:

Protein S has been one of the least mechanistically understood amongst the vitamin K-dependent coagulation proteins, and diagnosis of protein S deficiency and quantification of the associated thrombotic risk are not straightforward. In this review, the regulation of thrombin generation by protein S and the pathophysiological implications of protein S deficiency are discussed in the light of recent findings on the anticoagulant function(s) of protein S.

RECENT FINDINGS:

Protein S expresses both activated protein C-dependent and activated protein C-independent anticoagulant activities, but the former is generally believed to be lost upon binding of protein S to C4b-binding protein. Recently it has been shown that protein S acts as a cofactor of tissue factor pathway inhibitor in the down regulation of factor X-activation, which provides a mechanistic basis for the activated protein C-independent anticoagulant activity of protein S in plasma. In addition, reevaluation of the role of the protein S/C4b-binding protein complex has demonstrated that C4b-binding protein-bound protein S does express activated protein C-cofactor activity, especially during the inactivation of factor Va Leiden.

SUMMARY:

These findings underscore the central role of protein S in the regulation of coagulation and may have important implications for the evaluation of the thrombotic risk associated with protein S deficiency.

• Authors: Elisabetta Castoldi, Tilman M Hackeng
• Journal: Current opinion in hematology (Curr Opin Hematol) Vol. 15 Issue 5 Pg. 529-36 (Sep 2008) ISSN: 1531-7048 [Electronic] United States
• PMID: 18695379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Protein S
• Thrombin

Topics

• Blood Coagulation
• Humans
• Protein S (physiology)
• Protein S Deficiency (physiopathology)
• Thrombin (metabolism)