Heterogeneity of human factor VIII. III. Transitions between forms of factor VIII present in cryoprecipitate and in cryosupernatant plasma.

Human factor VIII in plasma is a disperse protein consisting of a series of aggregates wih different molecular weight. VIIR:Ag and VIII:C are present in all forms, but VIIR:WF is confined to the highest molecular weight forms only. After cryoprecipitation of plasma the latter are recovered in the precipitate, and the lowest molecular weight forms remain in the supernatant. Disaggregation of high molecular weight forms of factor VIII was found in vitro upon repeated cryoprecipitations. The disaggregation was detected only when the original low molecular weight forms were removed. The additional low molecular weight forms possessed VIII:C and VIIR:WF was lacking. The reverse process of aggregation of low molecular weight factor VIII to more highly aggregated forms was not observed. Exchange of VIII:C between high and low molecular weight fractions was demonstrated by gel chromatography of mixtures of hemophilic cryoprecipitate and normal concentrated cryosupernatant, and vice versa, at physiologic ionic strength. This suggests that VIII:C and VIIR:Ag are weakly and noncovalently linked in normal conditions. This was further supported by the dissociation of VIII:C from VIIIR:Ag and VIIIR:WF upon gel chromatography and cryoprecipitation at pH 6.2 The dissociation could be reversed by readjustment of the pH.