Fig. 1.

Major protease-mediated reactions in mammalian coagulation. Black Roman numerals represent plasma protease zymogens, with activated proteases indicated by a lower case ‘a’. Cofactors are represented by numerals in black ovals. White arrows indicate reactions involving FXI/XIa. Coagulation is initiated at an injury site by binding of plasma factor (F) VIIa to tissue factor (TF), which is present on cells underlying blood vessel endothelium. FVIIa/TF activates FX to initiate thrombin generation and fibrin formation, and also FIX to sustain coagulation through activation of FX. In some situations, FIX activation by FXIa is also required. FXI may be activated by more than one protease, but probably is most important during consolidation of coagulation rather than its initial phase.