[Protein C, protein S and heparin cofactor II--their significance as the regulatory factors in the blood coagulation cascade].
One of the major regulatory mechanisms operating in the blood coagulation cascade is the thrombomodulin-protein C anticoagulant pathway. It consists of thrombin, thrombomodulin, protein C (PC) and protein S (PS), and is initiated when the circulating zymogen PC is converted to activated PC (APC) by a thrombin-thrombomodulin complex on the surface of endothelial cells. The formed APC in the presence of its co-factor PS, downregulates the coagulation cascade by proteolytic inactivation of the procoagulant cofactors Va and VIIIa, and also enhances the fibrinolysis system by inhibition of plasminogen activator inhibitor 1. PS circulates in plasma in two forms in dynamic equilibrium. One is the free protein (approximately 40% of total PS in normal plasma) which has the APC cofactor activity; the other is the protein reversibly complexed to C4b-binding protein (C4bp), a regulatory component of the complement system. When bound to C4bp, PS can no longer function as a cofactor of APC. As complexing of PS with C4bp is regulated by the law of mass action, elevation of C4bp leads to reduced levels of free (active) PS. In comparison with antithrombin III, heparin cofactor II contributes less in neutralizing thrombin and has higher affinity to dermatan sulfate on the surface of vascular smooth muscle cells. Therefore, it is regarded as an extravascular antithrombin. Clinical evidence that these regulatory factors function as natural anticoagulants derives from the observation of patients with congenital deficiency of each factor suffering from severe venous and anterial thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Shinmyozu
K
K
Division of Blood Transfusion Medicine, Kagoshima University Hospital.
D001777:Blood Coagulation / Q000502:physiology*; D015844:Heparin Cofactor II / Q000502:physiology*; D006801:Humans; D011486:Protein C / Q000502:physiology*; D017293:Protein S / Q000502:physiology*
D011486:Protein C; D017293:Protein S; D015844:Heparin Cofactor II