FVII circulates in plasma mostly in the zymogen form; about 1% of plasma FVII is found in the active serine protease form FVIIa (FVIIa) (Morrissey JH et al. 1993). Upon tissue injury or inflammation, the coagulation process is initiated by exposure of the cell surface–anchored TF at an injury site to circulating blood (Langer F & Ruf W 2014; Ansari SA et al. 2019). The extracellular part of TF binds both FVII and FVIIa with very high affinity and specificity in a Ca²⁺-dependent manner (Ruf W et al. 1991; Kelley RF et al. 2004; Vadivel K& Bajaj SP 2012; Prasad R & Sen P 2018). The complex formed between TF and plasma FVII or FVIIa initiates the coagulation protease cascade by converting the zymogens FIX and FX to the active proteases FIXa and FXa, which are involved in the generation of thrombin. The allosteric binding of TF to FVIIa greatly increases the enzymatic activity of FVIIa, as revealed by a 20- to 100-fold increase in the rate of amidolysis of small, chromogenic peptidyl substrates (Broze GJ Jr & Majerus PW.1980; Butenas S et al. 1994; Higashi S et al. 1996). The TF:FVII zymogen complex has low but measurable proteolytic activity on factor X, suggesting that this complex initiates TF-dependent clotting through a minimal generation of factor Xa, which in turn catalyzes the activation of FVII from plasma. (Rao LV et al. 1986). As factor VIIa accumulates, TF:FVIIa complexes also form, accelerating the process (Nemerson Y 1988). A second model, building on the observation that normal plasma contains low levels of activated FVIIa constitutively, suggests that complexes with FVIIa form immediately at the onset of clotting (Rapaport SI and Rao LV 1995). The two models are not mutually exclusive, and in any event, the central roles of TF and FVIIa in generating an initial supply of factors IXa and Xa, and the self-limiting nature of the process due to the action of TFPI, are all well-established.