Stability of factor VIII concentrates after reconstitution

Abstract

Adjusted-dose continuous infusion of factor VIII (F VIII) has recently been shown to reduce the doses of the factor in patients undergoing surgery by 50-75%. The main limitation of this method has been the instability of factor concentrates. All manufacturers are recommending infusion of the concentrate within hours after reconstitution. We studied the stability of 15 different lyophilized F VIII products. Reconstituted samples were stored for periods of 4, 24, and 72 hr and 1, 2, 3, and 4 weeks at temperatures of 4-8 degrees C, 20-23 degrees C, and 37 degrees C in their original glass containers and in plastic tubes and then frozen. Assays were performed in duplicate, using a one-stage clotting method and a chromogenic assay for F VIII, with all samples from a single concentrate in the same run. Activation of the coagulation factor occurred in some concentrates, more often at 4-8 degrees C than at 20-23 degrees C or 37 degrees C. The stability of all products was substantially better than that declared by the manufacturers. Several concentrates 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 for continuous infusion.