During the initiation phase of coagulation, partial cleavage of FV at Arg737 and Arg1046 is catalyzed by either FXa or trace amounts of thrombin (reviewed by Camire RM & Bos MHA, 2009). This cleavage disrupts the inhibitory intramolecular interaction within FV by removing the N‑terminal basic region (FV (738‑1046)) while exposing the acidic region (AR (1047-1573)) of the B domain. At this stage, partially cleaved, procoagulant‑active FVa intermediates are generated. While FVa intermediate species exhibit the prothrombinase cofactor activity by binding FXa, their function is tightly regulated by tissue factor pathway inhibitor α (TFPIα), which binds with high affinity to the exposed AR of FVa intermediate species (Wood JP et al., 2013; van Doorn P et al., 2017; Petrillo T et al., 2021; Mohammed BM et al., 2024). Interaction with TFPIα prevents the cleavage of FV intermediate at Arg1573, inhibiting its prothrombinase cofactor activity (Wood JP et al., 2013; van Doorn P et al., 2017; Petrillo T et al., 2021; Mohammed BM et al., 2024). The final cleavage at Arg1573, primarily mediated by thrombin, completely removes the inhibitory B domain fully converting FV into its activated form, FVa, which binds FXa with higher affinity (Bunce MW et al., 2013; Bos MHA & Camire RM, 2012; Ruben EA et al., 2021; Mohammed BM et al., 2023, 2024).