This treatment-related complication occurring in ~30% of severe hemophilia A and ~3% of severe hemophilia B patients is a major challenge to the effective hemostatic management of these patients.63 While the recent introduction of the bispecific monoclonal antibody, emicizumab for use in FVIII inhibitor patients represents a significant advance in the management of these patients, there is still a sense that regaining immunologic tolerance to FVIII, to allow a reintroduction of FVIII treatment in these patients, is preferable. This evidence concerns the gene F8 and hemophilia A.