{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T01:36:01Z","timestamp":1772933761493,"version":"3.50.1"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"crossref","award":["26461593"],"award-info":[{"award-number":["26461593"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"crossref","award":["18K07885"],"award-info":[{"award-number":["18K07885"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Emicizumab 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.<\/jats:p><jats:p>\n          Aim\u2003To assess the risk of excessive thrombus formation associated with BPAs and emicizumab under high shear conditions.<\/jats:p><jats:p>\n          Methods\u2003Perfusion 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.<\/jats:p><jats:p>\n          Results\u2003Emicizumab (100\u2009\u03bcg\/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 \u00b5g\/mL; equivalent to 90 \u00b5g\/kg) together with emicizumab further promoted platelet interactions and fibrin formation ex vivo but did not induce excessive thrombus formation.<\/jats:p><jats:p>\n          Conclusion\u2003Emicizumab 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.<\/jats:p>","DOI":"10.1055\/s-0040-1716542","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T23:01:06Z","timestamp":1599692466000},"page":"279-286","source":"Crossref","is-referenced-by-count":6,"title":["Emicizumab Augments Thrombus Formation in Whole Blood from Patients with Hemophilia A under High Shear Flow Conditions"],"prefix":"10.1055","volume":"121","author":[{"given":"Hiroaki","family":"Yaoi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuaki","family":"Shida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehisa","family":"Kitazawa","sequence":"additional","affiliation":[{"name":"Research Division, Chugai Pharmaceutical Co., Kamakura, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Midori","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Nogami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/j.1365-2516.2012.02909.x","article-title":"Guidelines for the management of hemophilia","volume":"19","author":"A 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