The etiology of inhibitor development in children with severe hemophilia A

摘要: Patients with severe hemophilia, a deficiency of functional clotting factor VIII, typically suffer from joint and muscle bleedings spontaneously or after minor trauma. The bleeding tendency can be effectively corrected by intravenous substitution VIII products. However, about 25% patients hemophilia A develop inhibitors, anti-factor antibodies, that neutralize infused factor. More knowledge on the genetic environmental determinants risk inhibitor development may contribute to prediction patients’ individual risks developing inhibitors. Therefore, in this thesis we aimed identify patient-related factors A. In single center cohort study found type location F8 gene mutation were important development. systematic review meta-analysis pooled data 30 studies total 5383 patients, including 1029 provide more precise estimates relative for various types mutations That not only but also non-genetic play role is illustrated report discordant antibody response pair monozygotic twin brothers. Therefore further focused an international multi-center among born between 1990 2000 (the CANAL Study). intensive treatment such as during surgery major bleeds, was independent previously reported association early age at first exposure largely explained early, treatment. Furthermore, regular prophylaxis appeared protect against Contrary several earlier reports, plasma-derived products considerable concentrations VWF did confer lower inhibitory antibodies than recombinant switching product brands increase risk. To examine dose, frequency time starting incidence inhibitors set up large, 606 2010. findings suggested does affect It may, however, prevent late especially low mutations. All doses frequencies used our carried similar risks. After studying 20 years still many questions remain open. needed, it condition possibly even prevention If are able development, morbidity will greatly improved. Moreover, then hinder cure therapy.