Coagulation System

Coagulation is a complex process that responds to injury by the rapid formation of a clot. Coagulation can be initiated via the extrinsic or intrinsic pathways. The extrinsic pathway begins when an injury exposes platelets to collagen in the vessel wall and plasma factor VIIa (FVIIa) to extravascular tissue factor (TF). Platelets aggregate at the site of injury to form the primary hemostatic clot. TF binds FVIIa and accelerates the activation of FXa. Activated FXa assembles with cofactors FVa and FVIIIa on the surface of aggregated platelets leading to generation of thrombin (FIIa). Thrombin catalyzes the production of fibrin (FG) which creates a clot that reinforces the primary platelet clot.The intrinsic pathway starts with the binding of prekallikrein and high-molecular weight kininogen (HMWK) to activate FXIIa. A cascade of activations leads to the production of FXIa followed by FIXa and FXa. From this point on the intrinsic and extrinsic pathways are common.The coagulation system includes a number of control mechanisms to maintain a fine balance between formation and dissolution of a clot. Plasmin is one such protein that is required for dissolution of the fibrin clot. Plasmin is activated by tissue plasminogen activator (tPA) and urokinase. Other regulatory proteins include the SERPINs which inhibit thrombin, plasmin and tPA. Protein C, protein S and thrombomodulin together degrade FVa and FVIIIa. Thus the coagulation system responds to injury through a cascade of activation events leading to the formation of a clot which is eventually degraded and resorbed through the process of fibrinolysis.