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. 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. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
CITATION STYLE
Castoldi, E., & Hackeng, T. M. (2008, September). Regulation of coagulation by protein S. Current Opinion in Hematology. https://doi.org/10.1097/MOH.0b013e328309ec97
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