The Regulation of Natural Anticoagulant Pathways

TLDR

Vascular endothelium prevents clotting by expressing thrombomodulin, which converts thrombin into activated protein C that inactivates factors Va and VIIIa, linking coagulation to inflammation. Homozygous protein C deficiency in infants causes severe thrombotic complications, confirming the physiological importance of the protein C anticoagulant pathway.

Abstract

Vascular endothelium plays an active role in preventing blood clot formation in vivo. One mechanism by which prevention is achieved involves a cell surface thrombin-binding protein, thrombomodulin, which converts thrombin into a protein C activator. Activated protein C then functions as an anticoagulant by inactivating two regulatory proteins of the coagulation system, factors Va and VIIIa. The physiological relevance of the protein C anticoagulant pathway is demonstrated by the identification of homozygous protein C-deficient infants with severe thrombotic complications. Recent studies suggest that this pathway provides a link between inflammation and coagulation.