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. 2011 Feb 12;11(1):83–94.

Figure 1:

Figure 1:

The current model of the blood coagulation cascade. There are two blood coagulation pathways, the contact activation or “intrinsic” pathway and the primary or “extrinsic” pathway. These multicomponent processes are illustrated as enzymes, inhibitors, zymogens, or complexes. The contact activation pathway has no known bleeding cause associated with it; thus, this pathway is considered accessory to haemostasis. On injury to the vessel wall, tissue factor, the cofactor for the extrinsic tenase complex, is exposed to circulating FVIIa and forms the extrinsic tenase. FIX and FX are converted to their serine proteases FIXa and FXa, which then form the intrinsic tenase and the prothrombinase complexes with their cofactors, respectively. The combined actions of the intrinsic and extrinsic tenase and the prothrombinase complexes lead to an explosive burst of the key enzyme thrombin (IIa). In addition to its multiple procoagulant roles, thrombin also can act in an anticoagulant capacity when combined with the cofactor thrombomodulin in the protein Case complex. The product of the protein Case reaction, activated protein C (APC), inactivates the cofactors FVa (cofactor for FXa) and FVIIIa (cofactor for FIXa). The cleaved species, FVai and FVIIIai, no longer support the respective procoagulant activities. Once thrombin is generated through procoagulant mechanisms, thrombin cleaves fibrinogen (releasing fibrinopeptides A and B [FPA and FPB]) and activates FXIII to form a cross-linked fibrin clot. Thrombin–thrombomodulin also activates a thrombin activate-able fibrinolysis inhibitor that slows fibrin degradation by plasmin. The procoagulant response is downregulated at various stages by the stoichiometric inhibitors, tissue factor pathway inhibitor (TFPI) and antithrombin III (AT-III). TFPI serves to attenuate the activity of the extrinsic tenase trigger of coagulation. AT-III directly inhibits thrombin, FIXa, and FXa. The accessory pathway provides an alternate route for the generation of FIXa. Thrombin has also been shown to activate FXI. The fibrin clot is eventually degraded by plasmin yielding soluble fibrin peptides.