Advances in Hemophilia A Management

Hemophilia A is an inherited insufficiency of Factor VIII (FVIII), one of the critical clotting factors. The gold standard for the management of moderate-to-severe hemophilia A is prophylaxis using regular replacement therapy with clotting factor concentrates. Compared with conventional treatment, extended half-life products reduce the burden of frequent factor replacement injections. Of note, up to 30% of patients with hemophilia A receiving prophylactic factor infusions develop "inhibitors," neutralizing anti-FVIII autoantibodies. Therapeutic options for patients with hemophilia A and inhibitors include the immune tolerance induction (ie, eradication of inhibitors) and the management of acute bleeds with bypassing agents and/or emicizumab. Emicizumab is a biphasic monoclonal antibody mimicking activated FVIII, approved for patients with hemophilia A with/without inhibitors. Gene therapy is an emerging therapy for hemophilia A, essentially curing patients with hemophilia A or transforming them to a milder phenotype by establishing continuous endogenous expression of FVIII after one-time treatment.