FVII/rFVIIa competition for TF and activation of FVII dictate zymogen inhibition. (A) Theoretical simulations of FXa generation in an ideal system in which FVII and rFVIIa do not compete for TF (horizontal lines) and FVII cannot be activated to FVIIa (sloped curves). (B) Left panel shows activation of coagulation with sTF (133pM), which possesses low affinity for FVII and rFVIIa and mimics a system that lacks competition for TF (representative TG experiment from n = 2; data from 2 wells). Phospholipids (4μM) were added to compensate for the lower cofactor activity of sTF. Right panel shows comparison of the experimental data (dotted lines indicate measured TG peak height) from left panel to simulations under the same conditions (lines indicate simulated integral of FXa generation). (C) Left panel shows the strong inhibitory effect on rFVIIa by FVIIai, (FVIIai replaces FVII) mimicking a system without FVII activation (representative experiment from n = 2; data from 2 wells). Right panel shows comparison of experimental data (dotted lines indicate measured TG) from left panel to simulations under the same conditions (lines indicate simulated integral of FXa generation).