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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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