Representation of the FXa residues Val17 and Ile16 (purple) buried in the FXa active site adjacent to Ser195, His57, and Asp102. Ile16 interacts with Asp194 (dashed green line) forming the oxyanion hole (indicated as +). FXa variants induce zymogenicity to different degrees (Ile16Thr > Ile16Leu > Val17Met). The greater the zymogenicity, the weaker the inhibitor binding (red) and the longer the plasma half-life. This provides a toolkit of prohemostatic FXa variants that potentially broadens the applicability of FXa to different clinical settings involving bleeding.