Although the spectrum of bleeding manifestations can be variable, from superficial ecchymosis to lethal hemorrhage in the central nervous system [124], the phenotype is primarily determined by the residual amount of the deficient coagulation factor, with severe disease defined as <1%, moderate with 1–5% and mild hemophilia with 6–40% FVIII or FIX [122]. This evidence concerns the gene F8 and hemophilia.