INTRODUCTION: Monitoring extended half-life (EHL) factor (F) VIII and FIX products is complex, as discrepant results are obtained in different laboratory assays. AIM: To provide an overview on assay accuracy based on a re-assessment of previously published data as well as laboratory results of EHL spiking experiments for specific factor assays and thrombin generation (TG). METHODS: Previously published data on specific EHL-assay combination accuracy were re-assessed, applying uniform acceptable bias cutoffs at specific factor activity levels. Accuracy of EHL measurement was determined for six routinely used FVIII assays for spiked efmoroctocog alfa and rurioctocog alfa pegol as well as four FIX assays for spiked eftrenonacog alfa, albutrepenonacog alfa and nonacog bèta pegol. TG was performed on these samples to evaluate haemostatic potential. RESULTS: Re-assessment of previously published data showed insufficient accuracy for many EHL-assay combinations. Measurement results of nine previously undescribed EHL-assay combinations did not meet accuracy criteria for the entire tested factor activity range; results for other EHL-assay combinations were in many cases comparable to previous reports. TG on spiked efmoroctocog alfa and rurioctocog alfa pegol showed increased peak height (PH) and area under the curve (AUC) at higher factor activity level compared to diluted NPP FVIII. TG of eftrenonacog alfa was comparable to diluted NPP FIX but increased for albutrepenonacog alfa and nonacog bèta pegol. CONCLUSION: Accuracy of many routine FVIII or FIX assays is insufficient, and selection of the correct test is essential for producing reliable results. The haemostatic potential of EHL may deviate from the labelled potency according to TG results.
Stroobants et al. (Wed,) studied this question.