F8 and hemophilia A: Among the environmental factors, the role of the so-called “danger-signals” (e.g., vaccination, hemarthrosis, surgery) at the time of FVIII infusion in the development of inhibitors has attracted the interest of the scientific community, and offered a possible explanation for the intriguing question of why only a fraction of patients with severe hemophilia A develop an immune response to infused FVIII (5).