Activation Of Coagulation Factors And Thrombin Generation

As platelet adherence and activation are occurring, tissue factor forms a complex with factor VII and activated factor VIIa that cleaves both factors IX and X. Additionally, factor IX, activated by tissue factor, activates additional factor X, a reaction in which factor VIII serves as a cofactor. Factor Xa along with cofactor Va activates prothrombin (factor II) to thrombin (factor IIa). The production of thrombin precipitates fibrin formation, the final process ofcoagulation. Thrombin converts fibrinogen into fibrin monomers. Thrombin also activates platelets, converts factor V into Va, factor XI into XIa, and factor VIII into VIIIa (after VIII dissociates from vWF). The fibrin monomers polymerize to form fibrin strands that in turn terminate the factor XIII-mediated crosslinking to form a "mature" fibrin network (Fig. 2).

Fig. 2. A cell-based model of coagulation is initiated on tissue factor bearing cells, followed by assembly of clotting proteins on a template of activated (and aggregated) platelets that leads to thrombin (factor Ila) generation. Vascular thromboresistance, governed by antithrombin III, protein C, and TFPI, attenuates thrombin development, as does plasmin generated by tPA and uPA. This system of checks and balances is vital for maintaining vascular integrity and tissue-level hemostasis. (From ref. 2.)

Fig. 2. A cell-based model of coagulation is initiated on tissue factor bearing cells, followed by assembly of clotting proteins on a template of activated (and aggregated) platelets that leads to thrombin (factor Ila) generation. Vascular thromboresistance, governed by antithrombin III, protein C, and TFPI, attenuates thrombin development, as does plasmin generated by tPA and uPA. This system of checks and balances is vital for maintaining vascular integrity and tissue-level hemostasis. (From ref. 2.)

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