{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:06:40Z","timestamp":1788926800645,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["24K10935"],"award-info":[{"award-number":["24K10935"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["25K11065"],"award-info":[{"award-number":["25K11065"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["25K19236"],"award-info":[{"award-number":["25K19236"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with haemophilia (PwH) complicated with atrial fibrillation require direct oral anticoagulants (DOACs) to prevent thrombosis, but still require haemostatic management to control bleeding. However, specific recommendations for managing bleeding in PwH with inhibitors (PwH\u2010inh) receiving DOACs remain lacking. In Japan, plasma\u2010derived (pd\u2010) factor (F)VIIa\/FX products are available for clinical management of PwH\u2010inh, and may also be beneficial for haemostatic treatment in PwH\u2010inh receiving DOACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To assess coagulation potential of pd\u2010FVIIa\/FX or other bypassing agents (BPAs) using an in vitro plasma model of PwHA\u2010inh receiving DOACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>FVIII\u2010deficient plasma was preincubated with anti\u2010FVIII inhibitor (termed \u2018FVIII\u2010depleted\u2019). Pd\u2010FVIIa\/FX (1.5\u00a0\u00b5g\/mL as FVIIa), recombinant (r)FVIIa (2.2\u00a0\u00b5g\/mL), activated prothrombin complex concentrates (aPCC; 1.3 IU\/mL), or FX preparation (520\u00a0nM) were added to FVIII\u2010depleted plasmas supplemented with apixaban (100\u00a0ng\/mL) or edoxaban (100\u00a0ng\/mL). A similar model was prepared using plasma samples spiked with emicizumab (50\u00a0\u00b5g\/mL). Coagulation potential was assessed utilizing thrombin generation assay (TGA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The addition of pd\u2010FVIIa\/FX to FVIII\u2010depleted plasmas supplemented with DOACs increased TG potential to near\u2010normal range, irrespective of the presence of emicizumab. However, the addition of rFVIIa or FX alone to the FVIII\u2010depleted plasma with DOACs exhibited coagulation potential below the normal range. The addition of aPCC and emicizumab to FVIII\u2010depleted plasmas with DOACs enhanced TG potential above the normal range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pd\u2010FVIIa\/FX improved coagulation potential in the in vitro model plasma of PwHA\u2010inh spiked with DOACs, irrespective of concomitant emicizumab. The clinical efficacy and safety of pd\u2010FVIIa\/FX require further evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70402","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:30:21Z","timestamp":1788924621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma\u2010Derived Factor VIIa\/Factor X Improves Thrombin Generation Potential in a Plasma Model of Haemophilia A Supplemented With Direct Oral Anticoagulants"],"prefix":"10.1111","author":[{"given":"Shigeharu","family":"Oh","sequence":"first","affiliation":[{"name":"Medical Science of Thrombosis and Bleeding Disorder Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Medical Science of Thrombosis and Bleeding Disorder Nara Medical University  Kashihara Nara Japan"},{"name":"Department of Pediatrics Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Onishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisuke","family":"Takami","sequence":"additional","affiliation":[{"name":"Medical Affairs Section KM Biologics Co., Ltd  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotoshi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Medical Affairs Section KM Biologics Co., Ltd  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Nogami","sequence":"additional","affiliation":[{"name":"Medical Science of Thrombosis and Bleeding Disorder Nara Medical University  Kashihara Nara Japan"},{"name":"Department of Pediatrics Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"e335","DOI":"10.1055\/s-0039-1698756","article-title":"Catheter Ablation for Atrial Fibrillation in Patients With Hemophilia or Von Willebrand Disease","volume":"3","author":"Van der Valk P. 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