ArticleResearch and practice in thrombosis and haemostasis2024
NXT007-mediated hemostatic potential is suppressed by activated protein C-catalyzed inactivation of activated factor V.
Article in Research and practice in thrombosis and haemostasis, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Trial
- Next-generation FVIIIa-mimetic bispecific antibody NXT007: evaluation in preclinical models of hemostasis and thrombosis.Blood advances · 2026Article
- Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies.International journal of laboratory hematology · 2025Review
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Background: Activated protein C (APC) inactivates activated factor (F) V (FVa) and FVIIIa. NXT007, an emicizumab-based engineered therapeutic bispecific antibody, enhances the coagulation potential of FVIII-deficient plasma (FVIIIdef-plasma) to near normal levels. However, little is known about the effect of APC-induced inactivation in NXT007-mediated hemostatic function. Objectives: To investigate the contribution of APC-mediated reactions to NXT007-driven hemostasis. Methods: In pooled normal plasma (PNP) or FVIIIdef-plasma spiked with NXT007 (10 μg/mL), effects of APC (0-16 nM) were measured using a thrombin generation assay (TGA). The direct effects of APC on cofactor activity of NXT007 or FVIIIa in a FXa generation assay were also measured. The FVdef-plasma and FV Leiden plasma (FV Results: The APC dose-dependent suppression effect in TGA of FVIIIdef-plasma spiked with NXT007 was similar to that of PNP. FXa generation with NXT007 was not impaired by the addition of APC, suggesting that the APC-induced reaction in TGA with NXT007 was attributed to the direct inactivation of FVa. The addition of APC to FVIII-depleted FVdef-plasma, along with NXT007 and various FV concentrations, showed a similar attenuation to PNP. The NXT007-driven thrombin generation in FVIII-depleted FV Conclusion: NXT007 did not impair APC-mediated downregulation of FVa in FVIIIdef-plasmas, regardless of the presence of FV mutation with APC resistance.
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