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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3559

Title: Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, potentiates coagulation function in factor XI-deficient plasma in vitro.
Other Titles: 第IX(a)因子および第X因子に対する二重特異性抗体であるエミシズマブはin vitroで第XI因子欠乏血漿における凝固機能を増強する
Authors: Minami, Hiroaki
Nogami, Keiji
Yada, Koji
Ogiwara, Kenichi
Furukawa, Shoko
Soeda, Tetsuhiro
Kitazawa, Takehisa
Shima, Midori
Keywords: clot waveform analysis
factor XI deficiency
thrombin generation assay
Issue Date: Jan-2019
Publisher: John Wiley and Sons, Inc.
Citation: Journal of thrombosis and haemostasis Vol.17 No.1 p.126-137 (2019 Jan)
Abstract: Essentials Emicizumab mimics factor (F)VIIIa cofactor function, augments the intrinsic tenase activity. We assessed the emicizumab-driven hemostatic function in FXI-deficient plasmas. Emicizumab improved the coagulation potentials in severe FXI-deficient plasma. Emicizumab may provide a possibility for clinical application in patients with FXI deficiency. SUMMARY: Background Patients with factor (F)XI deficiency commonly present with markedly prolonged activated partial thromboplastin times (APTT), although bleeding phenotypes are heterogeneous. Emicizumab, a bispecific monoclonal antibody to FIX/FIXa and FX/FXa, mimics FVIIIa cofactor function on phospholipid (PL) surfaces. Antibody reactions were designed, therefore, to augment mechanisms during the propagation phase of blood coagulation. Aim To assess emicizumab-driven hemostatic function in FXI-deficient plasmas. Methods and Results Standard ellagic acid (Elg)/PL-based APTTs of different FXI-deficient plasmas (n = 13; FXI activity, < 1 IU dl-1 ) were markedly shortened dose dependently by the presence of emicizumab. To further analyze the effects of emicizumab, clot waveform analysis (CWA) in FXI-deficient plasmas with emicizumab, triggered by tissue factor (TF)/Elg demonstrated improvements in both clot times, reflecting the initiation phase, and coagulation velocity, which represents the propagation phase. Emicizumab also enhanced the TF/Elg-triggered thrombin generation in FXI-deficient plasmas dose-dependently although the degree of enhancement varied in individual cases. Thrombin generation with either FVII-deficient plasma or FIX-deficient plasma treated with anti-FXI antibody showed little or no increase by the co-presence of emicizumab, suggesting that the accelerated thrombin generation in FXI-deficient plasmas by emicizumab should depend on the FIXa-involved coagulation propagation initially triggered by FVIIa/TF. The ex vivo addition of emicizumab to whole blood from three patients with severe FXI deficiency demonstrated modest, dose-dependent improvements in Ca2+ -triggered thromboelastograms (NATEM mode). Conclusion Emicizumab appeared to improve coagulation function in severe FXI-deficient plasma, and might provide possibilities for clinical application in patients with FXI deficiency.
Description: 博士(医学)・乙第1427号・平成31年3月15日
© 2018 International Society on Thrombosis and Haemostasis
This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/jth.14334], which has been published in final form at [http://dx.doi.org/10.1111/jth.14334]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
URI: http://hdl.handle.net/10564/3559
ISSN: 15387933
Academic Degrees and number: 24601B1427
Degree-granting date: 2019-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2018年度

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