Summary
The formation of factor VIII antibodies is a major problem for replacement therapy
of haemophilia A patients. Antibodies occur in 5-30% of patients with severe haemophilia
A. The reason for antibody formation is still unknown. In this study we correlate
for the first time different factor VIII gene mutations, stop- and missense mutations,
large and small deletions and intrachromosomal intron 22 recombinations to antibody
formation. A total of 364 patients with known inhibitor status of our institute, of
the database, and of 3 studies representing intron-22-inversion data are included.
The results show that the risk for developing factor VIII antibodies is strongly related
to stop mutations, large deletions and intrachromosomal recombinations. A probable
explanation 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 well as possible therapeutic effects, are
discussed.
