CO-41 | COMPARISON OF COAGULATION AND CHROMOGENIC METHODS IN PHARMACOKINETICS WITH EXTENDED HALF-LIFE FACTOR VIII

R. Pastorino^1|2, F. Bocchi^1|2, G. Murante^1|2|3, S. Bergonzi^1|2|3, M. Capetta^1|2|3, F. Valeri^2|3, C. Dainese^2|3, A. Valpreda⁴, B. Bruno^1|3, A. Borchiellini^2|3 | ¹Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy; ²Regional Centre for Thrombotic and Hemorrhagic Diseases, AOU Città della salute e della Scienza di Torino, Italy; ³Division of Hematology, AOU Città della Salute e della Scienza, University of Turin, Italy; ⁴Central Lab Baldi and Riberi, AOU Città della salute e della Scienza di Torino, Italy

Background and Aims. Personalized prophylaxis is still considered the standard of care for severe hemophilia A. Replacement prophylaxis can now rely on extended half-life factor VIII concentrates (FVIII-EHL), very effective but difficult to monitor. For some of them, differences in Factor VIII levels are found using different dosage methods, and it is still unclear which is the optimal assay. For each pharmacokinetic, performed as an essential step in the patient's therapeutic pathway, we investigated a) whether, for some concentrates, the differences between methods highlighted a more suitable method for monitoring recovery in vivo; b) if our data matched the manufacturer’s recommendation for monitoring.
Materials and Methods. A total of 56 pharmacokinetic studies were performed. For each timepoint, plasma FVIII levels were assessed on an ACL TOP 750 (Werfen Company - Barcelona, Spain) using the following methods: 1. One-stage clotting assay (OSA) with SynthasIL reagent. 2. Chromogenic substrate assays (CSA) with Coamatic Factor VIII.
Results. A sufficient number to compare results between methods was reached only for the pharmacokinetics with 3 concentrates: 2 FVIII-EHL (Turoctocog Alfa and Damoctocog Alfa Pegol, both B domain deleted) and a single-chain FVIII (Lonoctocog Alfa). Turoctocog Alfa (16 kinetics) and Lonoctocog Alfa (8 kinetics), in line with literature data, highlighted higher FVIII levels when tested with CSA. However, for Lonoctocog Alfa levels found with CSA, they are not double compared to those with OSA (as indicated in the technical data sheet), and moreover, the differences at 24 hours seem to disappear. Instead, Efmoroctocog Alfa (despite only 4 kinetics having been evaluated) at some timepoints did not show significant differences between OSA and CSA. For all these concentrates, the same behavior (differences or equivalences) was observed for all patients. But for the kinetics with Damoctocog Alfa Pegol (11 kinetics), OSA and CSA highlighted differences but with heterogeneous behavior between patients. The numerically significant kinetics are reported in the histograms of Figure 1.
Conclusions. To offer the best personalized replacement prophylaxis, it is essential to know whether in vivo factor levels can be monitored interchangeably with CSA and OSA (and which reagent for aPTT) or necessarily with one of these. The availability of a product-specific laboratory standard could eliminate the differences and become crucial when a concentrate presents heterogeneity in behavior among patients and the most appropriate method is unpredictable.