INHIBITORS IN HEMOPHILIA PATIENTS - CURRENT STATUS AND MANAGEMENT

The development of inhibitor antibodies is a long-standing, well-docum ented complication of coagulation factor replacement therapy and is di fficult to treat. Previous estimates of 5-15% of patients developing i nhibitors may be low, since newer data suggest a wider range of occurr ence. Factors that appear to affect inhibitor development include the severity of hemophilia, age, genetics, and, possibly, the type of repl acement therapy administered. Recent studies raise the concern that re combinant factor therapies may be associated with more rapid developme nt and higher levels of inhibitors in previously untreated patients. H owever, results of different studies are often difficult to compare ow ing to differences in methodology and populations studied. Further stu dies standardized in design and methods are clearly needed. Management of patients with inhibitors involves control of acute bleeding episod es and, over the long term, induction of immune tolerance for the coag ulation replacement therapy. Many with low or moderate levels of inhib itors may be treated simply by administering higher doses of clotting factor. Other therapies appropriate for those with high levels of inhi bitors include porcine F VIII and factor VIII ''bypassing'' agents, su ch as recombinant factor VIIa. Long-term immune tolerance has been ach ieved through the high-dose ''Bonn'' regimen and immunosuppressive reg imens such as the ''Malmo'' method. Although management of inhibitor p atients has improved, it still represents a major challenge. Further r esearch is needed to identify which patients will develop inhibitors a nd tolerance, as well as to develop better methods to manage, reduce, or eliminate inhibitors from these patients. (C) 1994 Wiley-Liss, Inc.