TAILIEUCHUNG - Chapter 059. Bleeding and Thrombosis (Part 2)

Coagulation is initiated by tissue factor (TF) exposure, which, with factor (F)VIIa, activates FIX and FX, which in turn, with FVIII and FV as cofactors, respectively, results in thrombin formation and subsequent conversion of fibrinogen to fibrin. Thrombin activates FXI, FVIII, and FV, amplifying the coagulation signal. Once the TF/FVIIa/FXa complex is formed, tissue factor pathway inhibitor (TFPI) inhibits the TF/FVIIa pathway, making coagulation dependent on the amplification loop through FIX/FVIII. Coagulation requires calcium (not shown) and takes place on phospholipid surfaces, usually the activated platelet membrane. The immediate trigger for coagulation is vascular damage that exposes blood to TF. | Chapter 059. Bleeding and Thrombosis Part 2 Coagulation is initiated by tissue factor TF exposure which with factor F VIIa activates FIX and FX which in turn with FVIII and FV as cofactors respectively results in thrombin formation and subsequent conversion of fibrinogen to fibrin. Thrombin activates FXI FVIII and FV amplifying the coagulation signal. Once the TF FVIIa FXa complex is formed tissue factor pathway inhibitor TFPI inhibits the TF FVIIa pathway making coagulation dependent on the amplification loop through FIX FVIII. Coagulation requires calcium not shown and takes place on phospholipid surfaces usually the activated platelet membrane. The immediate trigger for coagulation is vascular damage that exposes blood to TF that is constitutively expressed on the surfaces of subendothelial cellular components of the vessel wall such as smooth-muscle cells and fibroblasts. TF is also present in circulating microparticles presumably shed from cells including monocytes and platelets. TF binds the serine protease factor VIIa the complex activates factor X to factor Xa. Alternatively the complex can indirectly activate factor X by initially converting factor IX to factor IXa which then activates factor X. The participation of factor XI in hemostasis is not dependent on its activation by factor XIIa but rather on its positive feedback activation by thrombin. Thus factor XIa functions in the propagation and amplification rather than in the initiation of the coagulation cascade. Factor Xa which can be formed through the actions of either the tissue factor factor VIIa complex or factor IXa with factor VIIIa as a cofactor converts prothrombin to thrombin the pivotal protease of the coagulation system. The essential cofactor for this reaction is factor Va. Like the homologous factor VIIIa factor Va is produced by thrombin-induced limited proteolysis of factor V. Thrombin is a multifunctional enzyme that converts soluble plasma fibrinogen to an insoluble fibrin matrix. .

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