Counteracting coagulation: Inhibitor development in hemophilia A

Hemophilia A is a X-linked hereditary bleeding disorder that affects approximately one in 6,000 males world-wide. It is caused by a deficiency and/or dysfunction of clotting factor VIII, leading to fragile blood clots that predispose patients to an increased bleeding tendency. Nowadays, hemophilia A can be treated with the intravenous administration of factor VIII concentrates (replacement therapy). Unfortunately, in a considerable number of patients, replacement therapy leads to the development of antibodies towards factor VIII (inhibitors) - a major complication of treatment. Inhibitors render factor VIII concentrates ineffective and jeopardize the treatment and prevention of bleeding episodes, resulting in a greater rate of complications, costs and disability.
This thesis focuses on inhibitor development in hemophilia A and addresses risk factors and immunological mechanisms driving inhibitor development. The findings of this thesis emphasize the importance of increased knowledge on the immunological response preceding inhibitor development and underlines the need for the identification of early laboratory biomarkers. This will open up new opportunities for preventive measures and will help to identify targets for novel eradication strategies.