F8 and hemophilia: ,166 Whereas FIX is endogenously synthesized in hepatocytes, FVIII is synthesized predominantly in liver sinusoidal endothelial cells, such that FVIII is ectopically expressed in clinical trials.167, 168, 169, 170 Hemophilia patients experience recurrent, spontaneous, or trauma-induced bleeding classically into joints, resulting in disabling arthropathy.