Factor VIII (formerly referred to as antihemophilic globulin and Factor VIIIc) is a large glycoprotein (320kD) that circulates in plasma at approximately 200ng/ml. Synthesized in the liver, the majority of Factor VIII is cleaved during expression resulting in a heterogeneous mixture of partially cleaved forms of F.VIII ranging in size from 200-280kD. The F.VIII is stabilized by association with von Willebrand Factor to form a F.VIII-vWF complex required for normal survival of F.VIII in vivo (T1/2 of 8-12 hours). F.VIII is a pro-cofactor that is activated through limited proteolysis by thrombin. I n this process F.VIIIa dissociates from vWF to combine with activated Factor IX, calcium and a phospholipid surface where it is an essential cofactor in the assembly of the Factor X activator complex. Once dissociated from vWF, F.VIIIa is susceptible to inactivation by Protein C and by non-enzymatic decay. Hemophilia A is a congenital bleeding disorder resulting from an X-chromosome linked deficiency of F.VIII. The severity of the deficiency generally correlates with the severity of the disease. Some hemophiliacs (~10%) produce a F.VIII protein that is partially or totally inactive. The production of neutralizing antibodies to F.VIII also occurs in 5-20% of hemophiliacs.