title: Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches.
abstract: The immune response to infused factor concentrates remains a major source of morbidity and mortality in the treatment of patients with hemophilia A and B. This review focuses on current treatment options and novel therapies currently in clinical trials. After a brief review of immune tolerance regimens, the focus of the discussion is on preventing bleeding in patients with hemophilia and inhibitors. Recombinant factor VIIa and activated prothrombin complex concentrates are the mainstays in treating bleeds in patients with inhibitors. Both agents have been shown to reduce bleeding episodes to a similar degree when infused prophylactically; however, individual patients may respond better to one agent over the other at any given time. The international immune tolerance trial revealed that a high-dose factor VIII regimen provided significantly better bleeding protection than the low-dose regimen. Given the high cost of treatment and the potential for a high-dose immune tolerance regimen to prevent bleeding in some patients, we discuss how we treat patients to maximize the prevention of bleeds while minimizing cost. Novel approaches to treatment of these patients are in development. These include agents that mimic factor VIII or augment thrombin generation by bypassing the inhibitor, as well as agents that inhibit the natural anticoagulants.
authors.affiliation: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Meeks
authors.affiliation: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA.
authors.forename: Glaivy
authors.initials: G
authors.lastname: Batsuli
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D015942:Factor VIIa / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy / Q000191:economics; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy / Q000191:economics; D006470:Hemorrhage / Q000097:blood / Q000191:economics / Q000517:prevention & control; D006801:Humans; D011994:Recombinant Proteins / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa