並列タイトル等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
タイトル（掲載誌）Thrombosis and haemostasis
一般注記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
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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
DOIinfo:doi/10.1055/s-0040-1716542
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