Indeed, the development of inhibitory antibodies to the infused factor represents the most severe complication in replacement therapy, particularly in hemophilias (A, ~30% of patients; B, 3–5%) [21,22], in which the use of rFVIIa is pivotal to bypass the deficient FIX/FVIII-dependent pathway and increase thrombin generation by restoring or boosting the FX-to-FXa conversion [23,24]. The gene discussed is F8; the disease is hemophilia.