Inhibitor development is a serious complication of haemophilia A treatment and there has been recent concern that the risk may be increased if patients are treated with more highly purified, modified or recombinant factor VIII products (Aledort. 1993; Scharrer & Neutzling, 1994; Hoyer, 1995; Briet f Rosendaal, 1994). There are no comparative studies, however, and the only available information comes from several prospective and retrospective evaluations that have identified a variable incidence, from 7% to 52%. A metaanalysis of eight retrospective reports found a ‘high response’inhibitor in 20% of the 451 patients with severe haemophilia A who had been treated with crude or intermediate factor VIII concentrates (Briet et al, 1994). The incidence is higher, of course, if’low response’and transient (Allain & Frommel, 19 76) inhibitors are also included. It is now recognized that transient inhibitors are occasionally detected when patients are tested every 3-6 months, even when there are no symptoms of factor VIII resistance (Bray et al. 1994; Lusher et aI. 1993; Addiego et ul, 1993; Peerlinck et al, 1993b)

Transient inhibitors usually have a minimal clinical effect and they disappear while the patient continues to receive regular factor VIII treatment. These observations lead to several questions. If frequent testing identifies inhibitory antibodies to factor VIII in 40-50% of patients with severe haemophilia A, is inhibitor formation the expected immune response to their treatment with a ‘foreign protein’? If so, why aren’t all patients at similar risk, and why do more than half of the patients have a transient inhibitor or a low response pattern? Finally, is the risk related to the factor VIII product used? This annotation will briefly summarize the available information.