The Effect of Storage of Whole Blood on the Association of Factor VIII‐Related Antigen and Factor VIII‐Coagulant Antigen

Abstract
To evaluate the extent of denaturation of factor VIII‐coagulant activity (VIII:C) during production of factor VIII concentrates, the factor VIII‐coagulant antigen (VIII:CAg)/VIII:C ratio was measured in plasma, cryoprecipitate and cryosupernatant from fresh and stored blood. This ratio was close to unity for both cryoprecipitate and other concentrates, suggesting that VIII:CAg is lost concurrently with VIII:C during cryoprecipitation and further fractionation.Storage of blood (18 h, 22°C) before processing resulted in a 30% loss of VIII:C from the separated plasma; however, VIII:CAg was not affected. In cryoprecipitate prepared from this plasma, VIII:C and VIII:CAg both were 30% lower than when prepared from fresh plasma. In the corresponding cryosupernatant, however, more VIII:CAg but less VIII:C was present compared with fresh material.Gel chromatography revealed that the rise of VIII:CAg in cryosupernatant prepared from stored blood, was due to an increased amount of VIII:CAg of low molecular weight, not being associated with factor VIII‐related antigen. Such an increase in dissociated VIII:CAg was not detected in the plasma prior to cryoprecipitation.It is concluded that during storage of blood, molecular changes are induced in the factor VIII‐VWF complex, possibly by limited proteolysis, which make the complex more liable to dissociation during subsequent cryoprecipitation.