Factor VIII-related activities in therapeutic concentrates

Recent studies have suggested that factor VIII exists in plasma as a complex containing two distinct antigens (VIII R:Ag and VIII C:Ag) and two different biological activities (VIII:C and VIII R:RCo). Concentrations of these four entities have been measured in all the different types of therapeutic material used for treatment of hemophilia and von Willebrand's disease. In all materials, the ratio of VIII R:Ag to VIII:C was greater than 1: however, there were significant differences between concentrates, and the lowest ratio was found in cryoprecipitate. In VIII R:Ag assays, the freeze-dried concentrates gave nonparallel dose-response curves compared with plasma, indicating alterations in molecular form during purification. Values for VIII C:Ag were much lower than the corresponding VIII R:Ag values, and ratios of VIII C:Ag to VIII:C were close to 1 in many of the concentrates, suggesting that the low yields of VIII:C in some production processes could result from losses of VIII:C molecules rather than from denaturation. Measurement of VIII R:RCo by a platelet counting method gave lower values in most concentrates than by an aggregometry technique. It is proposed that the platelet counting method may reflect closely the biological activity of the concentrates in treatment of von Willebrand's disease.