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. Author manuscript; available in PMC: 2012 Jul 12.
Published in final edited form as: Circulation. 2011 Jul 12;124(2):225–235. doi: 10.1161/CIRCULATIONAHA.110.952648

Figure 2. Schema of a two compartment model of the regulation of TF-initiated blood coagulation.

Figure 2

A cross section of a blood vessel showing the luminal space, endothelial cell layer and extravascular region is presented at the site of a perforation. The blood coagulation process in response is depicted in four stages. Tissue factor-factor VIIa complex, TF•VIIa; prothrombinase complex, Xa•Va; intrinsic factor Xase, VIIIa•IXa; ATIII-endothelial cell heparan sulfate proteoglycan complex bound to thrombin or factor Xa, HS•ATIII• (IIa or Xa); protein C bound to thrombomodulin-thrombin,TM•IIa•PC. Panel A. Perforation results in delivery of blood, and with it circulating factor VIIa and platelets, to an extravascular space rich in membrane bound TF. Platelets adhere to collagen and von Willebrand factor associated with the extravascular tissue, and TF binds factor VIIa, initiating the process of factor IX and factor X activation. Factor Xa activates small amounts of prothrombin to thrombin that activates more platelets and converts factor V and factor VIII to factor Va and factor VIIIa. Panel B. The reaction is propagated by platelet-bound intrinsic factor Xase and prothrombinase with the former being the principle factor Xa generator. Initial clotting occurs and fibrin begins to fill in the void in cooperation with activated platelets. Panel C. A barrier composed of activated platelets ladened with procoagualant complexes and enmeshed in fibrin scaffolding is formed. The reaction in the now filled perforation is terminated by reagent consumption attenuating further thrombin generation but functional procoagulant enzyme complexes persist because they are protected from the dynamic inhibitory processes found on the intravascular face. Panel D. View downstream of the perforation. Enzymes escaping from the plugged perforation are captured by antithrombin-heparan complexes and the protein C system is activated by residual thrombin binding to endothelial cell thrombomodulin, initiating the dynamic anticoagulant system. These intravascular processes work against occlusion of the vessel despite the continuous resupply of reactants across the intravascular face of the thrombus. From Orfeo, J. Biol. Chem. 280:42887–42896, 2005. With permission.