Approaches to the measurement of the in vivo response to Factor VIII concentrate infusion

The in vivo response to the infusion of 12 lots of Factor VIII Concentrate was determined in a five Centre collaborative study. The principal aim of the study was to compare the responses obtained, after infusion into a single haemophiliac, of several lots of Factor VIII Concentrate made by a newly licensed process with those obtained after the infusion of several lots of Factor VIII Concentrate made by a previous process. Factor VIII Concentrates made by two other manufacturers were also evaluated. There was considerable inter-laboratory variation in the results obtained for the Factor VIII:C content of both the Factor VIII Concentrates and the ex vivo plasma samples. However, on pooling the data, the mean in vivo recovery was not statistically different from the expected response based on the potency assigned by the manufacturers. These data indicate that the results from a single laboratory may not be reliable in ascertaining either the in vitro or the in vivo potency of a particular lot of Factor VIII Concentrate and suggest that in the absence of a Factor VIII inhibitor, the in vitro and in vivo potency of a particular lot of Factor VIII Concentrate should be ascertained by several laboratories and the results pooled. Such pooled information then can be used to predict reliably the in vivo recovery of factor VIII: C activity without resorting to a formal in vivo response study.