Standardization of factor VIII and von Willebrand factor in plasma: calibration of the WHO 5th International Standard (02/150).

Calibration of the 5th International Standard factor (F)VIII/von Willebrand factor in plasma (02/150) (5th IS) for five parameters [factor VIII: coagulant activity (FVIII:C); FVIII: antigen (FVIII:Ag), von Willebrand factor: antigen (VWF:Ag), von Willebrand factor: ristocetin cofactor (VWF:RCo), von Willebrand factor: collagen binding (VWF:CB)] was achieved through an international collaborative study involving 37 laboratories. Estimates calculated relative to the previous 4th IS and locally prepared normal plasma pools were not significantly different for estimates of FVIII:Ag, VWF:Ag, VWF:RCo and VWF:CB and hence mean values calculated relative to the 4th IS of 0.94, 0.91, 0.78 and 0.94 IU ampoule(-1), respectively, were assigned. However, estimates for FVIII:C relative to the fresh normal pools (mean 0.61 IU ampoule(-1)) were significantly lower than estimates relative to the 4th IS (mean 0.68 IU ampoule(-1)). In consideration of the good stability of FVIII:C in the 4th IS and the variability of estimates relative to the local pools it was agreed to assign the mean value obtained relative to the 4th IS of 0.68 IU ampoule(-1). For all five parameters the interlaboratory variability (geometric coefficient of variation, GCV%) was larger for estimates calculated relative to the normal pools (range 12.6-16.5%) when compared with estimates calculated relative to the 4th IS (range 3.5-8.3%). An accelerated degradation study performed in six laboratories indicated that the five calibrated parameters are extremely stable when ampoules are stored at -20 degrees C. Mean estimates of predicted loss per year at -20 degrees C ranged from 0% for VWF:CB to 0.029% for VWF:RCo. The 5th IS (02/150) was established by the World Health Organization in November 2003.