Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, potentiates coagulation function in factor XI-deficient plasma in vitro.

• Material Type: 博士論文
• Title: Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, potentiates coagulation function in factor XI-deficient plasma in vitro.
• Author/Editor: Minami, Hiroaki; Nogami, Keiji; Yada, Koji; Ogiwara, Kenichi; Furukawa, Shoko; Soeda, Tetsuhiro; Kitazawa, Takehisa; Shima, Midori
• Author Heading: Minami, Hiroaki; Nogami, Keiji; Yada, Koji; Ogiwara, Kenichi; Furukawa, Shoko; Soeda, Tetsuhiro; Kitazawa, Takehisa; Shima, Midori
• Publication, Distribution, etc.: John Wiley and Sons, Inc.
• Publication Date: 2019-01
• Publication Date (W3CDTF): 2019-01
• Alternative Title: 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
• Periodical title: Journal of thrombosis and haemostasis
• No. or year of volume/issue: 17 1
• Volume: 17
• Issue: 1
• Pages: 126-137
• ISSN (Periodical Title): ISSN : 1538-7933
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2019-03-15
• Dissertation Number: 乙第1427号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: clot waveform analysis; emicizumab; factor XI deficiency; plasma; thrombin generation assay
• Target Audience: 一般
• Note (General): type:Thesis; 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.; 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.; identifier:Journal of thrombosis and haemostasis Vol.17 No.1 p.126-137 (2019 Jan); identifier:15387933; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3559; identifier:Journal of thrombosis and haemostasis, 17(1): 126-137
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3559/1/01%e4%b9%991427%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3559/2/02%e4%b9%991427%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3559/6/03%e4%b9%991427%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/jth.14334
• Periodical Title (NCID): AA11811179; https://ci.nii.ac.jp/ncid/AA11811179
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU