Monitoring of Coagulation Potential of Efanesoctocog Alfa in Haemophilia A: Insights From Conventional and Global Hemostasis Assays

INTRODUCTION: Efanesoctocog alfa (Efa) is a high-sustained factor (F)VIII engineered to overcome von Willebrand factor (VWF)-dependent clearance, enabling once-weekly dosing. However, FVIII activity (FVIII:C) differs between the one-stage assay (OSA) and chromogenic substrate assay (CSA), and its relationship with global assays remains unclear. AIM: To assess the procoagulant potential in people with haemophilia A (PwHA) treated with Efa using conventional and global assays. METHODS: Plasma samples were collected from five PwHA treated with Efa. FVIII: C was assayed using OSA (RevohemAPTT, PathromtinSL at two institutions) and CSA. Clot waveform analysis (CWA) using RevohemAPTT SLA and ThromboCheck APTT SLA, thrombin generation assay (TGA), and rotational thromboelastometry were performed. Apparent equivalent FVIII:C (app-eq-FVIII:C) was derived from reference curves for cross-assay comparison. RESULTS: OSA-FVIII:C showed reagent- and site-dependent variability. Pathromtin-based FVIII:C aligned with Revohem-based values at one site but was 1.6-1.8-fold higher at the other. CSA values were higher; CSA/2.5 variably approximated OSA in this dataset. CWA increased consistently after administration, with Revohem-based assays higher than ThromboCheck-based assays, indicating reagent-dependent variation within CWA. TGA showed increased thrombin generation with interpatient variability, ranging from minimal to relatively marked increases; conversion to app-eq-FVIII:C was strongly parameter-dependent (time-to-Peak vs Peak-Th). Rotational thromboelastometry revealed heterogeneous responses, and app-eq-FVIII:C was frequently lower than OSA and CSA/2.5-derived values. CONCLUSION: Efa demonstrated assay-detected post-infusion increases; however, FVIII:C measurement varied across platforms and parameters. In this small exploratory cohort, these findings support assay-specific validation and cautious interpretation of inter-platform differences, rather than definitive conclusions regarding optimal monitoring strategy or direct clinical decision-making.