Figure 1

Initiation: Tissue Factor (TF) exposure binds factor VIIa. The TF-VIIa complex activates factor Xa and factor Va leading to conversion of prothrombin to thombin. Thrombin generation activates platelets and initiates a positive feedback loop. Amplification and Activation: At the site of injury, platelets bind to exposed collagen and undergo a cytoskeletal transformation to the activated phenotype. Thrombin cleaves the VWF from the VWF/VIII complex thus activating factor VIII. Propagation: The tenase complex is formed by factor VIII complexing with factor IX. Factor IXa is then able to diffuse towards the platelet surface where it binds the surface bound, activated factor VIIIa. The prothrombinase complex is formed by the platelet membrane bound factor Va complexing with Xa formed from the tenase complex. The activated platelet membrane can then catalyze the Xa/Va prothrombinase complex to convert large amounts of prothombin to thrombin. Thrombin performs the final step in the deposition of fibrin clot by cleaving fibrinogen to fibrin [20].