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    Poster Networking

    Hemophilia and Rare Bleeding Disorders

    Poster Networking Session

    PB0178 - Factor X enhances the coagulant potentials of Emicizumab.

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Presenting Author(s)

    • KS

      Kazuki Shimizu, MD (he/him/his)

      graduate student
      Department of Pediatrics, Nara Medical University
      Kashihara-shi, Nara, Japan

      • Co-Author(s)

    • Yuto Nakajima, MD PhD

      Assistant Professor
      Advanced Medical Science of Thrombosis and Hemostasis, Nara Medical University
      Kashihara, Nara, Japan

    • AO

      Akihisa Oda

      Postdoctoral Researcher
      Department of Pediatrics, Nara Medical University
      Kashihara, Nara, Japan

    • ET

      Eisuke Takami

      Assistant Manager
      Medical Affairs Section, KMBiologics Co., Ltd
      Kikuchi, Kumamoto, Japan

    • HN

      Hirotoshi Nakano

      Manager
      Medical Affairs Section, KMBiologics Co., Ltd
      Kikuchi, Kumamoto, Japan

    • KN

      Keiji Nogami

      Professor
      Nara Medical University, Nara, Japan
      Nara, Nara, Japan

    Background: Emicizumab (Emi) prophylaxis significantly reduces breakthrough bleedings in patients with hemophilia A (PwHA). Bypassing agents (BPAs) are used for haemostatic management in PwHA with inhibitors (PwHA-Inh). A combined product of plasma-derived factor (F)VIIa and FX (pd-FVIIa/FX; Byclot®) is available for haemostatic treatment of PwHA-Inh in Japan and the concomitant coagulant potentials of FVIIa/FX and Emi have already been reported. However, no information is available on the assessment of the concomitant coagulant potentials of FX only and Emi.

    Aims: To assess the concomitant coagulant potentials of FX and Emi by in vitro and in vivo studies.

    Methods: In vitro, FX and Emi were spiked into FVIII-deficient commercial plasma (Emi 50 µg/ml + FX 130/260/520/780/1040nM). Coagulant potentials were assessed using maximum coagulation velocity (Ad|min1|) in modified clot waveform analysis triggered by the mixture with aPTT and PT reagents, and peak thrombin (PeakTh) in thrombin generation assay triggered by the mixture with tissue factor (0.5 pM) and ellagic acid (0.3μM). In vivo, Emi (3.0mg/kg), human (h)FIX and hFX were intravenously injected to FVIII knockout mice (hFIX 100U/kg, hFX 100/200/500U/kg). Coagulant potentials in these FVIII knockout mice were assessed using the clot time and clot formation time (CT + CFT) in rotational thromboelastometry triggered by CaCl2.

    Results: Ad|min1| and PeakTh levels in FVIII-deficient plasmas spiked with Emi were increased in a FX concentration dependent manner. The highest Ad|min1| value was 7.03±0.24 (Normal range: 6.972±0.753) and PeakTh value was 460±83 nM (Normal range: 501±70 nM) in the presence of Emi and FX 780nM, indicating that these results were not beyond normal values. In animal studies, hFX dose-dependently shortened CT+CFT and shortest CT+CFT was observed when Emi and hFX 500U/kg were injected.

    Conclusion(s): The co-presence of FX and Emi could improve coagulation potential in PwHA.