Monitoring standard and extended half‐life products in hemophilia: Assay discrepancies for factor VIII and IX in pre‐ and postinfusion samples

Abstract

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Validation of factor VIII activity for monitoring standard and extended half‐life products and correlation to thrombin generation assays

“…In the current study, we used a different APTT reagent, containing ellagic acid instead of silica as activator, and a different coagulation analyser (Atellica Coag 360). These modifications make a direct comparison to the former study 9 difficult. However, the CSA‐1 reagent and calibrator were still the same, but the overestimation was less at high levels on the new instrument.…”

“…The strength of our study is that several products were tested under similar and comparable measurement conditions (instrument, reagent lots, calibration curves, etc.). As evaluated recently, a large assay discrepancy between FVIII CSA and OSA in post‐infusion samples was revealed 9 . In the current study, we used a different APTT reagent, containing ellagic acid instead of silica as activator, and a different coagulation analyser (Atellica Coag 360).…”

“…The use of thrombin generation measurements in haemophilia has been suggested for defining clinical phenotype, where factor activity levels lack correlation 24 . In this study, only spiked samples were tested in thrombin generation and it was seen recently by us and others that thrombin generation in post‐infusion samples has a larger variation, probably due to patient‐to‐patient variation 9,25 . The effects of sample volume and plasma dilution on thrombin generation have been evaluated by others and have led to an optimized Technothrombin assay using Ceveron alpha 26,27 .…”

“…Field studies of samples spiked with the currently approved EHL products have suggested that chromogenic assays recover the activity within acceptable limits for most levels 8 . Importantly, the choice of assay, reagent (activator and composition of phospholipid in the OSA but also calibrator) and analyser seem to influence the measured results 9 . Recent recommendations from the United Kingdom Haemophilia Centre Doctors’ Organisation guideline include local validation of each new product in order to find the appropriate factor assay that yields recovery within 20% for FVIII activity above 0.30 IU/ml or 30% for FVIII activity between 0.10–0.3 IU/ml 8 .…”

An Update on Laboratory Diagnostics in Haemophilia A and B

“…43 In contrast to the OSCA results, higher results for rFVIIIFc are obtained when samples are analysed by CSAs. 35,[42][43][44] It was assumed that these discrepancies stem from differences between the WHO IS for FVIII concentrate or plasma. 42 However, it is generally concluded that both the OSCA and the CSA may be used to safely monitor rFVIIIFc-based factor FVIII replacement therapies.…”