F8 and hemophilia: Epidemiological studies have outlined that supraphysiologic FIX:C is a modest independent risk-factor venous thrombosis (odds ratio [OR] 1.8−4.0) relative to supraphysiologic FVIII (OR 8.8−21.3).206, 207, 208 Multiple FIX-R338L trials achieved FIX:C in the range of normal or mild hemophilia without safety concerns.