2.9.2.1. Coagulation Inhibitors Protein C plays crucial role in controlling anticoagulation and is a vitamin K-dependent serine protease (zymogen). Protein S (a vitamin K- dependent glycoprotein) acts as a cofactor for APC (activated protein C) [133]. Protein C and S slow the coagulation cascade with inactivating coagulation factors such as factor Va and VIIIa. Protein C and protein S are division of a feedback control mechanism, in which excess thrombin production causes protein C activation, which in turn assists to stop the enlarging fibrin clot from occluding the vascular lumen. Particularly, thrombomodulin (the endothelial cell-surface protein) is a receptor for thrombin and protein C in the blood [134]. Thrombin loses
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This combination of properties makes AT III a very powerful and important endogenous anticoagulant molecule [133]. AT III inactivates thrombin and other coagulation factors such as IXa, Xa, XIa, and XIIa (where “a” denotes an “activated” factor) by forming a stoichiometric complex with the coagulation factor [134]. The catalytic-site serine of thrombin reacts with an arginine in the active center of AT III to form a covalent inactive complex [133]. These interactions are enhanced by a heparin-like molecule that is expressed at the surface of intact endothelial cells, ensuring that this mechanism is operative at all locations in the vascular tree except where endothelium is denuded at the site of vascular injury. These endothelial cell surface proteoglycans are referred to as “heparin-like” because they are the physiologic equivalent of the pharmacologic agent heparin. Heparin-like molecules on the endothelial cells bind to and activate AT III, which is thus primed to form a complex with the activated coagulation factors thereby making them inactive [134]. Once thrombin is bound to fibrin, it is resistant to AT III and even more so to ATIII-heparin complex
This combination of properties makes AT III a very powerful and important endogenous anticoagulant molecule [133]. AT III inactivates thrombin and other coagulation factors such as IXa, Xa, XIa, and XIIa (where “a” denotes an “activated” factor) by forming a stoichiometric complex with the coagulation factor [134]. The catalytic-site serine of thrombin reacts with an arginine in the active center of AT III to form a covalent inactive complex [133]. These interactions are enhanced by a heparin-like molecule that is expressed at the surface of intact endothelial cells, ensuring that this mechanism is operative at all locations in the vascular tree except where endothelium is denuded at the site of vascular injury. These endothelial cell surface proteoglycans are referred to as “heparin-like” because they are the physiologic equivalent of the pharmacologic agent heparin. Heparin-like molecules on the endothelial cells bind to and activate AT III, which is thus primed to form a complex with the activated coagulation factors thereby making them inactive [134]. Once thrombin is bound to fibrin, it is resistant to AT III and even more so to ATIII-heparin complex