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

Background Monitoring hemophilia treatment with extended half-life products is challenging for coagulation laboratories since factor assays may show substantial differences between results obtained with the one-stage assay (OSA) and the chromogenic substrate assay (CSA). Objectives The aim of this study was to evaluate and compare different factor assays and global coagulation methods. Methods Factor VIII (FVIII) and IX (FIX) activities and global assay parameters were analyzed in pre- and postinfusion samples (5 patients 2 samples/product/method). Results Samples containing FVIII products (NovoEight, Elocta, and Nuwiq) gave higher levels when measured with CSA compared to OSA. The correlation was excellent (r 2 ≥ .97) while biases of 42%-72% of mean (CSA-OSA) were obtained. With FVIII (OSA) as independent variable, the correlations to kaolin clot time (CT) and thrombin generation assay (TGA) peak were modest (r2 = .71-.72 and .64-.65, respectively), except for Nuwiq for which there was a poor correlation to TGA peak (r 2 = .08). Samples containing Alprolix, a FIX product, gave a smaller difference between activity levels (CSA-OSA), and the correlation was excellent (r 2 = .96). With FIX (CSA) as independent variable for both Alprolix and Refixia, the correlations to Innovin CT and TGA peaks were weak (r 2 = .33-.45 and .44-.76, respectively). Conclusions Our data show that factor activity assays differ between methods used and agents. These discrepancies indicate the value of having more than one type of assay available in the coagulation laboratory when monitoring hemophilia treatment with extended half-life products. Global assays gave complementary information indicated by the modest correlations to factor activities.