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20-400c

Endothelial bound 0.4-0.6 71-1096 95-1256 0.5

"Enzymatic activity: serine protease. •"Activity in plasma (%). ■Activity expressed as nM/L.

"Enzymatic activity: serine protease. •"Activity in plasma (%). ■Activity expressed as nM/L.

Fig. 11-4. Major inhibitory proteins of coagulation. TFPI, AT, protein C, and protein S are depicted with their target coagulation factor substrates. Abbreviations: TFPI, tissue factor pathway inhibitor; AT, antithrombin. h = inhibition.

inhibiting activated factors V and VIII (Figure 11-4). Binding of thrombin to thrombomodulin on endothelial cells of small blood vessels neutralizes the procoagulant activities of thrombin and activates protein C. Protein C binds to a specific receptor, and the binding augments the activation of protein C by thrombin. Activated protein C inactivates factors Va and Villa in a reaction that is greatly accelerated by the presence of free protein S and phospholipids, thereby inhibiting the generation of thrombin. Free protein S itself has anticoagulant effects: It inhibits the prothrombinase complex (factor Xa, factor Va, and phospholipid), which converts prothrombin to thrombin and inhibits the complex of factor IXa, factor VIIIa, and phospholipid, which converts factor X to factor Xa.

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