Perioperative management in patients with hemophilia receiving fitusiran, an investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia

Introduction: Hemophilia is a bleeding disorder characterized by ineffective clot formation due to insufficient thrombin generation. Fitusiran is a subcutaneously (SC) administered investigational RNA interference (RNAi) therapeutic targeting antithrombin (AT) as a means to improve thrombin generation (TG) and promote hemostasis in patients with hemophilia A or B with and without inhibitors. Previously reported data have shown that monthly administration of fitusiran led to dose dependent AT lowering, improved thrombin generation and decreased bleeding frequency. (Pasi et al. Blood . 2016.; Pasi et al. New Engl J Med . 2017.) Data from an open-label extension study demonstrated an encouraging safety and tolerability profile, including when used in combination with factor or bypassing agents to treat breakthrough bleeds. (Pasi et al. Res Pract Thromb Haemost . 2017.) The management of operative procedures while on novel, non-factor therapies for hemophilia, such as fitusiran, is of clinical interest. The purpose of this abstract is to describe details as reported by study investigators on the perioperative hemostatic management during dental/surgical procedures in patients with hemophilia receiving fitusiran in a clinical trial.