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2020年度 >
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http://hdl.handle.net/10564/3911
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タイトル: | Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII. |
その他のタイトル: | 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 |
著者: | Shimonishi, Naruto Nogami, Keiji Ogiwara, Kenichi Matsumoto, Tomoko Nakazawa, Fumie Soeda, Tetsuhiro Hirata, Michinori Arai, Nobuo Shima, Midori |
キーワード: | emicizumab fibrin clot structure fibrinolysis haemophilia A scanning electron microscopy |
発行日: | 2020年5月 |
出版者: | Wiley |
引用: | Haemophilia Vol.26 No.3 p.e97-e105 (2020 May) |
抄録: | 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. |
内容記述: | 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. |
URI: | http://hdl.handle.net/10564/3911 |
ISSN: | 13518216 |
DOI: | https://doi.org/10.1111/hae.13961 |
学位授与番号: | 24601A787 |
学位授与年月日: | 2021-03-15 |
学位名: | 博士(医学) |
学位授与機関: | 奈良県立医科大学 |
出現コレクション: | 2020年度
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