Clotting and chromogenic factor VIII assay variability in post‐infusion and spiked samples containing full‐length recombinant FVIII or recombinant factor VIII Fc fusion protein (rFVIIIFc)

• Published in: International journal of laboratory hematology 2019-04, Vol.41 (2), p.176-183
• Main Authors: Kitchen, Steve, Jennings, Ian, Makris, Mike, Kitchen, Dianne Patricia, Woods, Timothy A. L., Walker, Isobel D.
• Format: Article
• Language: English
• Subjects: Blood Coagulation; Blood Coagulation Tests; Clotting; Coagulation factors; Factor VIII - analysis; Factor VIII - pharmacology; Factor VIII deficiency; Fc receptors; Fusion protein; Hemophilia; Humans; Immunoglobulin Fc Fragments - analysis; Immunoglobulin Fc Fragments - pharmacology; Quality control; Recombinant Fusion Proteins - analysis; Recombinant Fusion Proteins - pharmacology
• ISSN: 1751-5521; 1751-553X
• DOI: 10.1111/ijlh.12940

Introduction Variability in FVIII measurement is a recognized problem. There are limited data for samples containing recombinant Factor VIII Fc fusion protein (rFVIIIFc). Many studies use samples for which factor concentrate has been spiked into FVIII deficient plasma in vitro. This approach requires validation. Aim/Methods Four samples were distributed in a UK National External Quality Assessment Scheme for Blood Coagulation (NEQAS BC) survey. One contained Advate (full‐length recombinant FVIII) (rFVIII) added to FVIII deficient plasma, one was from a severe haemophilia A patient after infusion of Advate, one was prepared by addition of rFVIIIFc (marketed as Elocta/Eloctate) to FVIII deficient plasma and the fourth was collected from a severe haemophilia A patient following rFVIIIFc (Eloctate) infusion. Fifty‐three haemophilia centres (UK and Scandinavia) performed one‐stage FVIII assays and 27 performed chromogenic FVIII assays. Results/Conclusions One‐stage assays gave significantly lower results than chromogenic assays by 7% (P