INCIDENCE OF INHIBITORS IN HEMOPHILIACS - A REVIEW OF THE LITERATURE

The development of factor VIII inhibitors remains one of the most serious complications in the treatment of patients with haemophilia A. Previous studies show a broad range of inhibitor prevalences (3.6-25.0%). Recent prospective studies, especially with monoclonal and recombinant factor VIII products, have given rise to discussion as to whether such preparations increase the incidence of inhibitors. Thirteen published inhibitor studies (as of January 1993) have, therefore, been analysed with regard to their design, results and evaluation. Most older studies were performed retrospectively and only evaluated the percentage of inhibitors in a poorly defined patient population at a given time. There was no clear differentiation between children and adults. Eleven studies showed incidence data, i.e. new inhibitors within the study period in a well-defined group. One study included only multi-transfused adults and the inhibitor incidence was only 2.4%. All other studies showed incidence rates of 5.7-32.0%. The new prospective studies, in particular, clearly confirm the early observation that young children with severe haemophilia A are at highest risk of inhibitor development after relatively few exposure days (median 9-15 days, one study 25 days). The early conclusion that monoclonally purified or recombinant factor VIII products may cause higher inhibitor rates was not confirmed by the newer studies. Previously untreated patients with severe haemophilia A showed inhibitor rates between 10% (Hemofil M) and 52% (various concentrates of different purity and viral inactivation method). One study evaluating such patients receiving only intermediate purity products or cryoprecipitate showed an incidence of 28%. The incidence in children with < 2% factor VIII activity (published in January 1993 and December 1992) for the two recombinant products was 29.2% and 18.0%, respectively.