Theories of Blood Coagulation: Basic Concepts and Recent Updates
Coagulation is the series of controlled reactions that leads to thrombin generation and fibrin formation. One model of hemostasis views the process as having three overlapping phases: initiation, amplification, and propagation. In initiation, factor VIIa/tissue factor activates both factors IX and X. Factor Xa promotes local thrombin generation that activates coagulation cofactors and platelets that adhere at the site of injury. Factor IXa combines with platelet surface factor VIIIa to activate factor X on the platelet surface. This factor Xa moves into a protected complex with factor Va to give a platelet burst of thrombin generation. Thrombin that moves outside the hemostatic plug binds to thrombomodulin on endothelial cells where it activates protein C which, with protein S, inactivates factors Va and VIIIa. This creates a downregulation of thrombin generation on healthy endothelium and localizes hemostasis to the area of injury.
