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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3832

Title: Emicizumab Augments Thrombus Formation in Whole Blood from Patients with Hemophilia A under High Shear Flow Conditions.
Other Titles: 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
Authors: Yaoi, Hiroaki
Shida, Yasuaki
Kitazawa, Takehisa
Shima, Midori
Nogami, Keiji
Keywords: emicizumab
thrombus formation
bypassing agents
flow chamber
Issue Date: 9-Sep-2020
Publisher: Thieme
Citation: Thrombosis and haemostasis Online ahead of print (2020 Sep 9)
Abstract: 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.
Description: 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"
URI: http://hdl.handle.net/10564/3832
ISSN: 03406245
Academic Degrees and number: 24601B1487
Degree-granting date: 2020-12-24
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2020年度

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