Figure 1

Cell surface coagulation complexes of the procoagulant and anticoagulant pathways. The coagulation pathways are initiated by tissue factor (TF), which serves as the allosteric activator of the enzyme coagulation factor VIIa (VIIa). The TF–VIIa complex binds substrate factor X (X) through multiple contacts at so-called exosites, leading to the formation of a fairly stable TF–VIIa–X complex in which substrate X is converted to product Xa. When Xa is released from this complex, it associates with the cofactor Va to form the Va-Xa (prothrombinase) complex, predominantly on activated platelets that expose procoagulant phospholipid binding sites for Va and Xa. The intrinsic factor VIIIa-IXa complex can generate additional Xa that further amplifies the burst of thrombin generation required for hemostasis. Cell surface receptor mediated events also govern activation of the anticoagulant protein C (PC) pathway, which is localized to endothelial cells. Thrombomodulin (TM) binds thrombin and switches the procoagulant properties of thrombin to anticoagulant functions. Endothelial PC receptor (EPCR) is the receptor for PC and activated protein C (APC), and promotes activation of PC by thrombin–thrombomodulin. When APC is released from EPCR, it can act as a systemic anticoagulant by cleaving cofactors Va and VIIIa on various cell types.