Schematic of the computational model of the tissue factor pathway.

The multicomponent processes encompassed in the computational model are illustrated as either: enzymes (open circle), inhibitors (hatched circle), zymogens (open boxes) or complexes (open ovals). Upon injury to the vessel wall, tissue factor, the cofactor for the extrinsic tenase complex, is exposed to circulating factor VIIa and forms the vitamin K dependent complex the extrinsic tenase. Factor IX and factor X are converted to their serine proteases factor IXa (FIXa) and factor Xa (FXa) which then form the intrinsic tenase and the prothrombinase complexes, respectively. The combined actions of the intrinsic and extrinsic tenase and the prothrombinase complexes lead to an explosive burst of the enzyme thrombin (IIa). The procoagulant response is down regulated by the stoichiometric inhibitors tissue factor pathway inhibitor (TFPI) and antithrombin (AT). TFPI serves to attenuate the activity of the extrinsic tenase trigger of coagulation. AT directly inhibits thrombin, FIXa and factor Xa. The proteins in which the concentrations from individual subjects are used are shown in red. Tissue factor in blue is arbitrarily set to 5 pM. Circulating FVIIa is set at 1% of the concentration of FVII from each individual.