Abstract
A high purity factor VIII/von Willebrand Factor (FVIII/vWF)concentrate (IMMUNATE*[STIM plus†])(n = 6 batches), and a high purityfactor IX (FIX) concentrate (IMMUNINE*[STIMplus]) (n = 7 batches), wereassessedin vitrofor their applicability to continuousinfusion. Parameters pertinent to continuous infusion wereinvestigated and included stability, sterility and, in the caseof FIX, the generation of potentially thrombogenic components.Four stationary or transportable mini infusion pumps, equippedwith polyethylene, polypropylene or polyvinylchloride plasticcomponents were used. The concentrates were reconstitutedwithout extra filling volume and perfused at12.5 mL h−1and1 mL h−1; sampling was carriedout at the start of the experiment and for up to 48 h.The FVIII procoagulant activity (FVIII:C) was assayed byamidolytic, 1‐stage and 2‐stage assays; vWF was examined forristocetin cofactor activity, antigen and multimers. The FIXcoagulation activity (FIX:C) was determined by a 1‐stagecoagulation assay; thrombogenicity potential was assessedinvivo(Wessler stasis model in rabbits) andinvitro(FIXa and nonactivated thromboplastin time).Reconstituted concentrate incubated under the same conditionsserved as a control. Both concentrates remained sterilethroughout the testing period. The perfused and control samplesremained stable, retaining over 95% of activity for FVIII:C andover 90% for FIX:C for up to 48 h. Intermittent decreaseof FVIII:C or FIX:C was not observed, suggesting no adsorptionof FVIII or FIX onto plastic surfaces during either short orlong‐term exposure. No thrombogenic components were detected inthe high purity FIX concentrate. Thus, under theinvitroconditions used, FVIII/vWF and FIX were found to besuitable for administration by continuous infusion.