Incidence of inhibitor Dewelopment in consecutiwely recruited sewere Hemophilia A and B Patients - a retrospective Single Centre Study

摘要

Hemophilia A (HA) and B (HB) are X-linked genetic disorders resulting in deficiencies of blood coagulation factors VIII and IX. In order to prevent joint bleedings and hemophilic arthropathy in hemophilia patients, a long-term prophylactic therapy with factor VIII or IX concentrates has been suggested. This coagulation factor substitution can be complicated by the development of antibodies against factor VIII or IX (sc. inhibitors).Based on a number of studies the incidence of antibody development in patients with severe hemophilia A (residual activity of factor VIII less than 1% of normal) has been estimated to be between 3.6% - 33% [Scharrer et al. 1993, Gilles et al. 1997]. These data suggest that up to one third of patients with severe hemophilia may develop an inhibitor sometime in their lives. However, among patients with hemophilia B, inhibitors are less frequent, affecting only 1% to 4% of the moderately and severely affected patients (Biggs et al. 1974, Ehrenforth et al. 1992). Is has been controversially discussed, whether the type of factor preparation used for substitution, namely plasma derived or recombinant concentrates, may influence the incidence of antibody development. No final prospective data are available [Kreuz, Auerswald personal correspondence]. Moreover, specific mutations in the factor VIII and IX genes like gross deletions or inversions, have been suspected to increase the risk for inhibitor development (Briet et al. 1994, Hoyer et al. 1995, Kavakli et al. 1998, Kreuz et al. 1996, Rasi et al. 1990, Scharrer et al., 1998,1999).