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In vitro and in vivo stability of diluted recombinant factor VIII for continuous infusion use in haemophilia A

Summary.  Factor VIII (FVIII) replacement by continuous infusion (CI) is used postoperatively or after significant bleeding. For young paediatric patients, CI may require FVIII dilution. Variable stabilities of diluted full‐length recombinant FVIII Kogenate® FS (KG‐FS) have been reported under different storage conditions. We investigated the recovery and stability of diluted KG‐FS in vitro and in vivo. Kogenate® FS was diluted to 50–120 U mL−1 and its recovery and stability in glass vials or polypropylene syringes was determined. Furthermore, stability of KG‐FS diluted to 80 U mL−1‘administered’ via single‐ and double‐pump mock CI systems was tested. Finally, the in vivo stability of KG‐FS diluted to ∼60 U mL−1 and administered postsurgically by CI with the double‐pump to a paediatric patient with severe haemophilia A undergoing implantable venous access device placement was investigated. Initial KG‐FS dilution resulted in a 10–20% FVIII loss; a further 25–30% loss occurred over 72 h in vials or syringes. With the double‐pump, 1 h recovery was 35%, increasing to 80% by 24 h; the initial losses were because of the Y‐infusion of a 10‐fold larger volume of saline concomitantly with the FVIII. In vivo, CI resulted in stable FVIII activity levels within the target range. These in vitro results are important for the generation of CI guidelines for diluted KG‐FS in the paediatric haemophilic population. That FVIII losses occur upon dilution and with the double‐pump does not preclude use of diluted KG‐FS. Indeed, stable FVIII levels were maintained when diluted KG‐FS was administered by CI with the double‐pump to a paediatric patient postsurgically.