1. A factor IX variant that functions independently of factor VIII mitigates the hemophilia A phenotype in patient plasma
- Author
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Viola J.F. Strijbis, Lorenzo G.R. Romano, Ka Lei Cheung, Jeroen Eikenboom, Ying Poi Liu, Andrew C. McCreary, Frank W.G. Leebeek, Mettine H.A. Bos, and Hematology
- Subjects
Hematology - Abstract
Background: Recombinant factor (F)IX-FIAV has previously been shown to function independently of activated FVIII (FVIIIa) and ameliorate the hemophilia A (HA) phenotype in vitro and in vivo. Objectives: The aim of this study was to assess the efficacy of FIX-FIAV in plasma from HA patients using thrombin generation (TG) and intrinsic clotting activity (activated partial thromboplastin time [APTT]) analyses. Methods: Plasma obtained from 21 patients with HA (>18 years; 7 mild, 7 moderate, and 7 severe patients) was spiked with FIX-FIAV. The FXIa-triggered TG lag time and APTT were quantified in terms of FVIII-equivalent activity using FVIII calibration for each patient plasma. Results: The linear, dose-dependent improvement in the TG lag time and APTT reached its maximum with approximately 400% to 600% FIX-FIAV in severe HA plasma and with approximately 200% to 250% FIX-FIAV in nonsevere HA plasma. The cofactor-independent contribution of FIX-FIAV was therefore suggested and confirmed by the addition of inhibitory anti-FVIII antibodies to nonsevere HA plasma, resulting in a FIX-FIAV response similar to severe HA plasma. Addition of 100% (5 μg/mL) FIX-FIAV mitigated the HA phenotype from severe to moderate (from
- Published
- 2023