Identifying Nongenetic Risk Factors for Inhibitor Development in Severe Hemophilia A

The development of inhibitory antibodies against infused factor VIII (FVIII) is a major challenge in hemophilia treatment. As the antibodies swiftly inactivate administered therapeutic FVIII concentrates, FVIII is no longer effective in controlling bleeding. To achieve adequate hemostasis, bypassing therapies are required, with accompanying clinical challenges and financial expense. Extensive research has aimed to elucidate the multifactorial etiology of inhibitor development. Both genetic and nongenetic causes have been identified. Identification of treatment-related risk factors would offer the possibility to modify treatment strategies in high-risk patients, thereby reducing the risk of inhibitor development. Have we presently gained sufficient knowledge to make a prediction of the inhibitor risk possible and justify changes in treatment regimens for specific patient groups? This review summarizes and evaluates the research findings on nongenetic risk factors of inhibitor development, with special focus on treatment-related factors.