Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII.

• Material Type: 博士論文
• Title: Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII.
• Author/Editor: Shimonishi, Naruto; Nogami, Keiji; Ogiwara, Kenichi; Matsumoto, Tomoko; Nakazawa, Fumie; Soeda, Tetsuhiro; Hirata, Michinori; Arai, Nobuo; Shima, Midori
• Author Heading: Shimonishi, Naruto; Nogami, Keiji; Ogiwara, Kenichi; Matsumoto, Tomoko; Nakazawa, Fumie; Soeda, Tetsuhiro; Hirata, Michinori; Arai, Nobuo; Shima, Midori
• Publication, Distribution, etc.: Wiley
• Publication Date: 2020-05
• Publication Date (W3CDTF): 2020-05
• Alternative Title: エミシズマブは凝固第VIII因子と同様にフィブリン構造およびその安定性を向上させる
• Periodical title: Haemophilia
• No. or year of volume/issue: 26 3
• Volume: 26
• Issue: 3
• Pages: e97-e105
• ISSN (Periodical Title): ISSN : 1351-8216
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2021-03-15
• Dissertation Number: 甲第787号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: emicizumab; fibrin clot structure; fibrinolysis; haemophilia A; scanning electron microscopy
• Target Audience: 一般
• Note (General): type:Thesis; Introduction: Emicizumab is an antifactor (F)IXa/FX bispecific antibody, mimicking FVIIIa cofactor function. Emi prophylaxis effectively reduces bleeding events in patients with haemophilia A. The physical properties of emicizumab-induced fibrin clots remain to be investigated, however. Aim: We have investigated the stability and structure of emicizumab-induced fibrin clots. Methods: Coagulation was initiated by activated partial thromboplastin time (aPTT) trigger and prothrombin time (PT)/aPTT-mixed trigger in FVIII-deficient plasma with various concentrations of emicizumab or recombinant FVIII. The turbidity and stability of fibrin clots were assessed by clot waveform and clot-fibrinolysis waveform analyses, respectively. The resulting fibrin was analysed by scanning electron microscopy (SEM). Results: Using an aPTT trigger, the turbidity was decreased and the fibrinolysis times were prolonged in the presence of emicizumab dose-dependently. Scanning electron microscopy imaging demonstrated that emicizumab improved the structure of fibrin network with thinner fibres than in its absence. Although emicizumab shortened the aPTT dramatically, the nature of emicizumab-induced fibrin clots did not reflect the hypercoagulable state. Similarly, using a PT/aPTT-mixed trigger that could evaluate potential emicizumab activity, emicizumab improved the stability and structure of fibrin clot in a series of experiments. In this circumstance, fibrin clot properties with emicizumab at 50 and 100 µg/mL appeared to be comparable to those with FVIII at ~12 and ~24-32 IU/dL, respectively. Conclusion: Emicizumab effectively improved fibrin clot stability and structure in FVIII-deficient plasma, and the physical properties of emicizumab-induced fibrin clots were similar to those with FVIII.; 博士（医学）・甲第787号・令和3年3月15日; © 2020 John Wiley & Sons Ltd.; This is the peer reviewed version of the following article: https://onlinelibrary.wiley.com/doi/10.1111/hae.13961, which has been published in final form at https://doi.org/10.1111/hae.13961. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.; identifier:Haemophilia Vol.26 No.3 p.e97-e105 (2020 May); identifier:13518216; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3911; identifier:Haemophilia, 26(3): e97-e105
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3911/1/01%e7%94%b2787%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3911/2/02%e7%94%b2787%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3911/3/03%e7%94%b2787%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/hae.13961
• Periodical Title (NCID): AA11030122; https://ci.nii.ac.jp/ncid/AA11030122
• 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