International comparative field study evaluating the assay performance of AFSTYLA in plasma samples at clinical hemostasis laboratories. (1st February 2018)

• Record Type: Journal Article
• Authors: St. Ledger, K.; Feussner, A.; Kalina, U.; Horn, C.; Metzner, H. J.; Bensen‐Kennedy, D.; Blackman, N.; Veldman, A.; Stowers, A.; Friedman, K. D.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 16:Number 3(2018)
• Page Start: 555
• Page End: 564
• Publication Date: 2018-02-01
• Subjects: drug monitoring -- factor VIII -- hemophilia A -- multicenter study -- recombinant proteins; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13932
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : Essentials AFSTYLA exhibits ≈50% underestimation in activity when the one‐stage (OS) assay is utilized. A field study compared the performance of AFSTYLA with Advate in factor VIII activity assays. AFSTYLA activity can be monitored with both the chromogenic substrate and the OS assay. The consistent OS underestimation allows for a conversion factor to be applied to OS results. Summary: Introduction: AFSTYLA (antihemophilic factor [recombinant] single chain) is a novel B‐domain truncated recombinant factor VIII (rFVIII). For AFSTYLA, an approximate 50% discrepancy was observed between results of the one‐stage (OS) and chromogenic substrate (ChS) FVIII activity assays. An investigation was undertaken to test whether there is a linear relationship between ChS and OS assay results that would allow reliable clinical interpretation of results independent of the assay method used. Aims: To provide confidence in future clinical monitoring, this field study investigated the performance of AFSTYLA and a full‐length rFVIII (Advate ® ) in FVIII activity assays routinely performed in clinical laboratories. Methods: The comparison of AFSTYLA and Advate was performed in an international, multicenter and blinded field study of simulated post‐infusion samples. The study documented the extent of variability between methods and laboratories and characterized the relationship between the ChS and OS assays. Results: Results from 23 laboratories demonstrate that intra and interlaboratory variability in OS assays were similar for both products. When comparing within the OS assay format, there was a similar and reagent‐correlated variability in response to different activators for both AFSTYLA and Advate. The OS underestimation was highly predictable and consistent across the complete range of FVIII plasma concentrations. Conclusion: Post‐infusion plasma AFSTYLA levels can be monitored in patients by the OS and ChS assays. The consistent and predictable difference between the two assay formats provides clinicians with adequate guidance on how to interpret the results of the OS assay using a single conversion factor.