ArticleResearch and practice in thrombosis and haemostasis2025
Factor X and combined factor VIIa/factor X augment coagulation potential in a plasma model of antithrombin-reduced hemophilia.
Article in Research and practice in thrombosis and haemostasis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Plasma-derived (pd) factor (F)VIIa/FX products are available for the hemostatic management of people with hemophilia with inhibitors in Japan. We have previously reported that FX alone augments emicizumab-driven hemostasis. Fitusiran is an investigational small interfering RNA that reduces antithrombin (AT) to rebalance hemostasis in people with hemophilia. The effects of supplementation with pd-FVIIa/FX or FX alone on coagulation potential in AT-reduced hemophilia remain to be clarified. Objectives: To assess the coagulation potential of pd-FVIIa/FX or FX using an Methods: Pd-FVIIa/FX (0.75 and 1.5 μg/mL as FVIIa), recombinant FVIIa (1.1 and 2.2 μg/mL), activated prothrombin complex concentrate (0.65 and 1.3 IU/mL), or FX (260 and 520 nM) were added to FVIII- or FIX-depleted AT-deficient plasmas at AT levels of 10% and 30% (AT-reduced model). Additionally, FX (0-1040 nM) was incubated with FVIII- or FIX-depleted FX-deficient plasmas to assess FVIIa/tissue factor (TF)-mediated FX activation. Coagulation potential was assessed by measuring thrombin generation (TG) and FXa. Results: The addition of pd-FVIIa/FX, activated prothrombin complex concentrate, or FX to the AT-reduced plasma model of people with hemophilia improved TG potential within the normal range. The addition of recombinant FVIIa, however, had little effect on TG in this model. The addition of FX to FVIII- or FIX-depleted FX-deficient plasma increased TG potential and FVIIa/TF-triggered FXa generation dose-dependently. Conclusion: Supplementation with FX or pd-FVIIa/FX enhanced FVIIa/TF-induced activation of FX and increased coagulation potential in the AT-reduced plasma model of people with hemophilia.
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