About Alloantibody Inhibitors

A possible complication of hemophilia A is the development of alloantibody inhibitors in patients treated with factor VIII. These inhibitors neutralize the hemostatic effect of the factor VIII replacement protein. Therefore, inhibitor development is regarded as one of the most important complications of hemophilia, both for the impact of disease on the patient and the ability of the physician to manage the condition.1 

Inhibitors develop in up to 35% of patients with severe hemophilia, with lower rates in mild and moderate disease.2 Patients are classified by inhibitor titer as either low or high responders.1 This classification is extremely important to treatment.

Immune tolerance induction (ITI) may be an effective technique to reset the immune system so it does not react to factor VIII treatments. The goal of immune tolerance therapy is to eventually “teach” the body to tolerate the factor and to not mount an immune response so that normal replacement therapy can be used to prevent or control bleeding.

A patient, usually with high inhibitor titers, receives regular infusions of factor VIII that continue for months or 2 or more years; a mean of 17 months has been reported.3,4

Each ITI patient on average uses 547,500 IU per year.5 As mentioned, the technique is effective in 70% to 80% of patients.6



References: 1. Mannucci PM, Abshire T, Dimichele D, Santagostino E, Blanchette V. Inhibitor development, immune tolerance and prophylaxis in haemophilia A—the need for an evidence-based approach. Haemophilia. 2006; 12:429–434. 2. Hay CR. The epidemiology of factor VIII inhibitors. Haemophilia. 2006;12(suppl 6):23–29. 3. DiMichele DM, Kroner BL. The North American Immune Tolerance Registry: practices, outcomes, outcome predictors. Thromb Haemost. 2002;87:52–57. 4. Mariani G, Kroner B.; Immune Tolerance Study Group (ITSG). Immune tolerance in hemophilia with factor VIII inhibitors: predictors of success. Haematologica. 2001;86:1186–1193. 5. Survey on Hemophilia Care and Price Monitoring, United States, Wave #18.Orange, CT: The Marketing Research Bureau Inc.;2008. 6. Dargaud Y, Negrier C. Haemophiliatherapies. Expert Opin Biol Ther. 2007;7:651–663.