The proteolytic activity of FVIIa is allosterically induced upon binding to TF exposed on the membrane surfaces of TF-bearing cells at sites of vascular injury (Bach R et al., 1986; Nakagaki T et al., 1991; Butenas S et al., 1996; Banner DW et al., 1996; Higashi S et al., 1996; Riewald M & Ruf W 2001; Kelley RF et al., 2004; Bajaj SP et al., 2006; Persson E & Olsen OH 2011; Madsen JJ et al., 2015; Sorensen AB et al., 2019; Madsen JJ & Olsen OH 2021). At the endothelial cell surface, TF:FVIIa catalyzes the formation of activated factors IXa (FIXa, F9a) and FXa (F10a) (Komiyama Y et al., 1990; reviewed in Vadivel K & Bajaj SP 2012). The phospholipid composition in the cell membrane regulates pro-coagulant activity of TF:FVIIa (Shaw AW et al., 2007; Muller MP et al., 2022). The TF:FVII zymogen complex has low (comparing to TF:FVIIa) but measurable proteolytic activity on factor X, suggesting that this complex can initiate the TF-dependent clotting at earlier stages through a generation of a small amount of factor Xa, which in turn catalyzes the proteolytic activation of FVII (Rao LV et al. 1986; reviewed by Rao LV & Rapaport SI 1988; Nemerson Y 1988). As factor VIIa accumulates, the formed TF:FVIIa complexes accelerate the process of FXa generation through a reciprocal activation of FXa and FVIIa, each one acting on the other. Upon activation, FXa can remain associated with the TF:FVIIa (or TF:FVII) complex, forming the ternary complexes TF:VII:FXa and TF:VIIa:FXa (Norledge BV et al., 2003; Venkateswarlu D et al., 2003; reviewed by Ruf W 2021). The docking models suggest that TF interacts with the gamma-carboxyglutamic acid (Gla) domain and epidermal growth factor (EGF)-like 1 domain of FX, while serine protease (SP) domain of FVII/FVIIa interacts with the Gla, EGF-2, and SP domains of FX. These interactions allow for the alignment of the active site of FVIIa with the substrate, leading to the cleavage of FX (Norledge BV et al., 2003; Venkateswarlu D et al., 2003; reviewed in Lee CJ et al., 2010; Vadivel K & Bajaj SP 2012). Besides generation of FXa, this ternary complex (1) proteolytically activates FVIII and thereby promotes the TF-independent mode of the clotting cascade, (2) activates protease-activated receptors (PARs) 1 and 2, influencing immune responses and inflammation, (3) and regulates the formation of the quaternary TF:FVIIa:FXa:TFPI complex with TF pathway inhibitor (TFPI), which blocks activities of both FXa and FVIIa (reviewed in Ruf W 2021).