Figure 1.

(a) Classic cascade/waterfall model of thrombin generation. Coagulation is initiated either through the intrinsic pathway (indicated by black arrows) or the extrinsic pathway (indicated by the light gray circle enclosing factor VIIa and tissue factor [TF]). Coagulation proteases and their precursors are indicated in black type, with a lower case ‘a’ indicating the active form. Cofactors are indicated in white type within dark gray ovals. The intrinsic pathway initates coagulation in the activated partial thromboplastin time (aPTT) assay, while the extrinsic pathway initiates coagulation in the prothrombin time (PT) assay. (b) A model of thrombin generation based on initiation through the factor VIIa/tissue factor (TF) complex. Major reactions involved in thrombin generation and hemostasis in most situations are indicated by white arrows. A feedback loop involving thrombin activation of factor XI to factor XIa, with subsequent activation of factor IX (black arrows) is required for hemostasis in some individuals, particularly when trauma involves tissues with high intrinsic fibrinolytic activity such as those of the urogenital tract.