tailieunhanh - Chapter 059. Bleeding and Thrombosis (Part 3)

Sites of action of the four major physiologic antithrombotic pathways: antithrombin (AT); protein C/S (PC/PS); tissue factor pathway inhibitor (TFPI); and the fibrinolytic system, consisting of plasminogen, plasminogen activator (PA), and plasmin. PT, prothrombin; Th, thrombin; FDP, fibrin(ogen) degradation products. [Modified from BA Konkle, AI Schafer, in DP Zipes et al (eds): Braunwald's Heart Disease, 7th ed. Philadelphia, Saunders, 2005.] Antithrombin (or antithrombin III) is the major plasma protease inhibitor of thrombin and the other clotting factors in coagulation. Antithrombin neutralizes thrombin and other activated coagulation factors by forming a complex between the active site of the enzyme and the. | Chapter 059. Bleeding and Thrombosis Part 3 Sites of action of the four major physiologic antithrombotic pathways antithrombin AT protein C S PC PS tissue factor pathway inhibitor TFPI and the fibrinolytic system consisting of plasminogen plasminogen activator PA and plasmin. PT prothrombin Th thrombin FDP fibrin ogen degradation products. Modified from BA Konkle AI Schafer in DP Zipes et al eds Braunwald s Heart Disease 7th ed. Philadelphia Saunders 2005. Antithrombin or antithrombin III is the major plasma protease inhibitor of thrombin and the other clotting factors in coagulation. Antithrombin neutralizes thrombin and other activated coagulation factors by forming a complex between the active site of the enzyme and the reactive center of antithrombin. The rate of formation of these inactivating complexes increases by a factor of several thousand in the presence of heparin. Antithrombin inactivation of thrombin and other activated clotting factors occurs physiologically on vascular surfaces where glycosaminoglycans including heparan sulfates are present to catalyze these reactions. Inherited quantitative or qualitative deficiencies of antithrombin lead to a lifelong predisposition to venous thromboembolism. Protein C is a plasma glycoprotein that becomes an anticoagulant when it is activated by thrombin. The thrombin-induced activation of protein C occurs physiologically on thrombomodulin a transmembrane proteoglycan binding site for thrombin on endothelial cell surfaces. The binding of protein C to its receptor on endothelial cells places it in proximity to the thrombin-thrombomodulin complex therefore enhancing its activation efficiency. Activated protein C acts as an anticoagulant by cleaving and inactivating activated factors V and VIII. This reaction is accelerated by a cofactor protein S which like protein C is a glycoprotein that undergoes vitamin K-dependent posttranslational modification. Quantitative or qualitative deficiencies of protein C or protein