HEMOPHILIA-A - MUTATION TYPE DETERMINES RISK OF INHIBITOR FORMATION

The formation of factor VII antibodies is a major problem for replacem ent therapy of haemophilia A patients. Antibodies occur in 5-30% of pa tients with severe haemophilia A. The reason for antibody formation is still unknown. In this study we correlate for the first time differen t factor VIII gene mutations, stop- and missense mutations, large and small deletions and intrachromosomal intron 22 recombinations to antib ody formation. A total of 364 patients with known inhibitor status of our institute, of the database, and of 3 studies representing intron-2 2-inversion data are included. The results show that the risk far deve loping factor VIII antibodies is strongly related to stop mutations, l arge deletions and intrachromosomal recombinations. A probable explana tion could be the complete lack of endogenous circulating factor VIII protein in these cases. Other factors that might be important for the pathogenesis of inhibitor formation, e. g. the antenatal period as wel l as possible therapeutic effects, are discussed.