Overview of inhibitors to factor VIII and IX.

The studies related to inhibitors of factor VIII and IX have clearly shown that these inhibitors are antibodies whether they arise in hemophiliacs lacking one of the factors or in patients with diseases associated with altered immune functions. Some of the most interesting data relates to the etiology of these inhibitors. If inhibitors are more likely to arise in CRM- hemophilia patients and if inhibitor development is familial, is it possible to define beforehand which patients are likely to develop inhibitors? If a subpopulation of patients at risk for inhibitor development could be identified, how would one prevent the event from occurring? Should these patients receive immunosuppressive agents prior to infusion of the missing factor? What is the relationship between the actual gene defect and inhibitor development? Is the prevalence of inhibitors in hemophilia B less common and if so are severely affected hemophilia A patients more likely to exhibit gross gene defects? Are there relationships between gene defect and immune response genes? Other major questions involve therapy. Can one induce specific immune tolerance at acceptable cost using low doses of factor concentrates or would it be better to develop other ways of eradicating inhibitors after they appear? What will be the future use of concentrates designed to by-pass the inhibitor, and is bypassing activity due to factors that are complexed to lipids or other substances that protect them from inhibitors? This overview has raised more questions than answers, but perhaps that is the purpose of an overview.