Background: Hemophilia A is a bleeding disorder results from genetic mutation in the coagulation factor synthesis process, which is critical for maintaining hemostasis. Hemophilia A, an X-linked disorder that affects males at a prevalence of 1:5000–10,00000, is the most frequent type and is caused by a deficiency of factor VIII (FVIII).

Replacement therapy for FVIII is still the cornerstone for treatment of hemophilia A. The main side effect of replacement therapy is the development of antibodies, which significantly reduces the therapeutic effectiveness by blocking FVIII activity. FVIII Inhibitors might be high or low titer. Risk factors, both genetic and non-genetic, influence the development of FVIII inhibitors. The types, prevalence, and risk factors of FVIII inhibitors are summarized in the current review.

Conclusion: Hemophilia A is an inherited disease due to decrease in FVIII synthesis. Accordingly, normal homeostasis is affected leading to bleeding according to the level FVIII and the site of bleeding. Meanwhile, treatment of hemophilia A by replacement factor may lead to inhibitor formation which is a major challenge.