Emicizumab Augments Thrombus Formation in Whole Blood from Patients with Hemophilia A under High Shear Flow Conditions.

• Material Type: 博士論文
• Title: Emicizumab Augments Thrombus Formation in Whole Blood from Patients with Hemophilia A under High Shear Flow Conditions.
• Author/Editor: Yaoi, Hiroaki; Shida, Yasuaki; Kitazawa, Takehisa; Shima, Midori; Nogami, Keiji
• Author Heading: Yaoi, Hiroaki; Shida, Yasuaki; Kitazawa, Takehisa; Shima, Midori; Nogami, Keiji
• Publication, Distribution, etc.: Thieme
• Publication Date: 2020-09-09
• Publication Date (W3CDTF): 2020-09-09
• Alternative Title: 高ずり応力下において、エミシズマブは血友病A 患者の全血の血栓形成を増加させる
• Periodical title: Thrombosis and haemostasis
• No. or year of volume/issue: 121 3
• Volume: 121
• Issue: 3
• Pages: 279-286
• ISSN (Periodical Title): ISSN : 0340-6245
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2020-12-24
• Dissertation Number: 乙第1487号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: emicizumab; FVIII; thrombus formation; bypassing agents; flow chamber
• Target Audience: 一般
• Note (General): type:Thesis; Background: Emicizumab is a bispecific antibody to factor (F) IXa and FX that mimics the FVIIIa cofactor function. Emicizumab prophylaxis markedly decreases bleeding episodes in patients with hemophilia A (PwHAs), irrespective of the presence of FVIII inhibitors. However, thrombotic microangiopathy (TMA) was reported when repeated high doses of activated prothrombin complex concentrates (aPCC) were concomitantly used with emicizumab. Although bypassing agents (BPAs) are vital in the hemostatic treatment for PwHAs with inhibitors, the mechanism of emicizumab-related TMA remains unclear. Aim: To assess the risk of excessive thrombus formation associated with BPAs and emicizumab under high shear conditions. Methods: Perfusion flow-chamber experiments under high shear conditions were performed using whole blood from PwHAs in the presence of emicizumab without or together with FVIII or BPAs ex vivo. Results: Emicizumab (100 μg/mL) added ex vivo to whole blood from PwHAs improved defective thrombus formation in a similar manner to that observed with the addition of recombinant FVIII at the early phase, while FVIII continued to be important at the later stages. aPCC (1.2 U/mL equivalent to 100 U/kg) or recombinant FVIIa (1.1 µg/mL; equivalent to 90 µg/kg) together with emicizumab further promoted platelet interactions and fibrin formation ex vivo but did not induce excessive thrombus formation. Conclusion: Emicizumab enhanced thrombin generation at local sites and improved defective hemostasis in whole blood from PwHAs under high shear conditions. Simple concomitant use of BPAs with emicizumab did not mediate excessive thrombus formation and remains an option for hemostatic management of emicizumab-treated PwHAs with inhibitors.; 博士（医学）・乙第1487号・令和2年12月24日; © 2020. Thieme. All rights reserved.; This is a non-final version of an article published in final form in "http://dx.doi.org/10.1055/s-0040-1716542"; identifier:Thrombosis and haemostasis vo.121 No.3 p.279-286 (2021 Mar); identifier:03406245; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3832; identifier:Thrombosis and haemostasis, 121(3): 279-286
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3832/1/01%e4%b9%991487%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3832/2/02%e4%b9%991487%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3832/8/03%e4%b9%991487%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1055/s-0040-1716542
• Periodical Title (NCID): AA00863137; https://ci.nii.ac.jp/ncid/AA00863137
• 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