Coagulation cascade. A simplified representation of the “coagulation cascade”. Note the role that the tenase complexes play in thrombin generation. The intrinsic tenase complex consists of factors VIIIa, IXa, and X on a phospholipid surface with phosphatidylserine exposure, usually a platelet, and facilitates the activation of factor X. The extrinsic tenase complex consists of factor VIIa, tissue factor, and factor X, likewise leading to the activation of factor X. Note the many feedback mechanisms of activation that thrombin performs. Although the generation and exposure of TF at the site of vascular endothelial is the primary initiator of coagulation via the extrinsic pathway, the intrinsic tenase pathway is important because active TF has only limited availability in vivo and TFPI’s constitutive activity inhibits the extrinsic tenase complex from generating adequate thrombin for a stable clot (see reference 19 for a more detailed treatment of this topic). In a PTT test, a test on which clot-based factor assays are built, phospholipid and calcium are added to a sample anticoagulated with sodium citrate (a calcium chelator that inhibits the Ca++ dependent steps as noted in the figure). Thrombin is added to the assay and further generated by the thrombin burst (see text). The activation of factor VIII or IX is the rate-limiting step in the assay. Factors are labeled by their traditional roman numeral. TF, tissue factor; TFPI, tissue factor pathway inhibitor; EPCR, endothelial protein C receptor; APC, activated protein C.