This figure illustrates the two pathways of in vivo thrombin generation that occur during initiation and maintenance of coagulation. Activation pathways are shown as black arrows; inhibitory pathways are shown here as interrupted red arrows.
- Initiation - The left-hand pathway illustrates initial thrombin generation. Following injury, tissue factor (TF) is liberated and binds to factor VIIa, activating both factor X and factor IX (not shown). Tissue factor-dependent coagulation is rapidly inhibited by tissue factor pathway inhibitor (TFPI), such that only a limited amount of thrombin is generated. Although a fibrin clot is formed, it is susceptible to fibrinolysis.
- Maintenance - The right-hand pathway illustrates how coagulation is maintained through a feedback loop. The small amount of thrombin generated initially activates platelets and factors V, VIII, and XI, leading to a burst of thrombin generation through activation of ten-ase and prothrombinase activity. These greater amounts of thrombin, in combination with thrombomodulin (TM), activate thrombin-activatable fibrinolysis inhibitor (TAFIa), increasing the resistance of the forming clot to fibrinolysis. Low levels of factor XI, VIII, or IX interfere with this feedback loop, resulting in reduced production of thrombin as well as a fibrin clot that is susceptible to fibrinolysis.
