STABILITY OF FACTOR-VIII CONCENTRATES AFTER RECONSTITUTION

Adjusted-dose continuous infusion of factor VIII (F VIII) has recently been shown to reduce the doses of the factor in patients undergoing s urgery by 50-75%. The main limitation of this method has been the inst ability of factor concentrates. All manufacturers are recommending inf usion of the concentrate within hours after reconstitution. We studied the stability of 15 different lyophilized F VIII products. Reconstitu ted samples were stored for periods of 4, 24, and 72 hr and 1, 2, 3, a nd 4 weeks at temperatures of 4-8 degrees C, 20-23 degrees C, and 37 d egrees C in their original glass containers and in plastic tubes and t hen frozen. Assays were performed in duplicate, using a one-stage clot ting method and a chromogenic assay for F VIII, with all samples from a single concentrate in the same run. Activation of the coagulation fa ctor occurred in some concentrates, more often at 4-8 degrees C than a t 20-23 degrees C or 37 degrees C. The stability of all products was s ubstantially better than that declared by the manufacturers. Several c oncentrates maintained factor activities above 80% of baseline for the entire period of 4 weeks at 4-8 degrees C or at 20-23 degrees C. The results demonstrate that many of the F VIII concentrates may be used f or continuous infusion. (C) 1994 Wiley-Liss, Inc.