Short ReviewPrevention of inhibitor development in hemophilia A in 2016. A glimpse into the future?

•The development of FVIII inhibitors is the most challenging complication of replacement therapy in hemophilia A.•The development of FVIII alloantibodies is a multifactorial process which involves genetic and acquired risk factors.•Among the non-genetic risk factors, an early intensive treatment carries the greater inhibitor risk.

Thanks to considerable progresses made over the last 30 years, hemophilia benefits from the most efficacious and safe treatment among the many monogenic inherited disorders. The most challenging complication of replacement therapy in hemophilia A is the occurrence of alloantibodies against infused factor VIII (FVIII), thus predisposing the patients to increased morbidity and disability. Extensive research in this field has definitively unraveled that development of inhibitors in hemophilia A is a complex and multifactorial process, in which inherited and environmental factors dynamically interact. This narrative review, after providing a concise overview about the main genetic and non-genetic risk factors, is aimed to focus on prediction risk models and preventive strategies for minimizing the risk of developing inhibitors in hemophilia A patients.