{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:48:02Z","timestamp":1780667282756,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T00:00:00Z","timestamp":1384819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Haemophilia patients with inhibitors require bypassing agents (<jats:styled-content style=\"fixed-case\">BPA<\/jats:styled-content>) like activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) to control bleeds. Adjunct tranexamic acid (<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>) may improve haemostasis. The objective of this study was to investigate safety and haemostatic effect of<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>given in combination with<jats:styled-content style=\"fixed-case\">BPA<\/jats:styled-content>. Healthy volunteers (<jats:italic>N<\/jats:italic>\u00a0=\u00a05) and haemophilia inhibitor patients (<jats:italic>N<\/jats:italic>\u00a0=\u00a06) were enrolled in a prospective case crossover design. Controls were treated with<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>20\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>orally (O.R.) Patients were treated with aPCC 75\u00a0IU\u00a0kg<jats:sup>\u22121<\/jats:sup>intravenous (I.V.) on day 1 followed by<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>20\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>O.R. combined with aPCC 75\u00a0IU\u00a0kg<jats:sup>\u22121<\/jats:sup>I.V. on day 2. A 14\u2010day washout occurred before crossover to rFVIIa 90\u00a0\u03bcg\u00a0kg<jats:sup>\u22121<\/jats:sup>I.V. \u00b1<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>. Safety evaluation and blood sampling processes were performed at baseline, 15, 30, 60, 120, 180 and 240\u00a0min post treatment. Primary outcome was maximum clot firmness (<jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>) evaluated by whole blood thromboelastometry using a<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content>\u00a0+\u00a0tissue plasminogen activator\u2010based assay. Healthy controls showed a 20\u2010fold increase in<jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>following<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>. Adjunct<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>to aPCC or rFVIIa induced a significant increase in<jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>(<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.0001) reaching levels indistinguishable from healthy controls treated with<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>(<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05). Infusion of aPCC or rFVIIa alone induced only 3\u201310 fold increase in<jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>from baseline, with a decline in<jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>starting after 60\u2013120\u00a0min.<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>did not increase the endogenous thrombin potential. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed. Combination of aPCC or rFVIIa with<jats:styled-content style=\"fixed-case\">TXA<\/jats:styled-content>normalizes clot stability in haemophilia patients with inhibitor as compared to healthy controls. No clinical or laboratory adverse events were observed.<\/jats:p>","DOI":"10.1111\/hae.12318","type":"journal-article","created":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T04:19:56Z","timestamp":1384921196000},"page":"369-375","source":"Crossref","is-referenced-by-count":35,"title":["Tranexamic acid as adjunct therapy to bypassing agents in haemophilia<scp>A<\/scp>patients with inhibitors"],"prefix":"10.1111","volume":"20","author":[{"given":"H. T. T.","family":"Tran","sequence":"first","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo Oslo Norway"},{"name":"Department of Haematology Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Baxter Healthcare Corporation Westlake Village CA USA"},{"name":"Haemostasis Research Unit Guy's and St Thomas' Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. J.","family":"Rea","sequence":"additional","affiliation":[{"name":"Haemostasis Research Unit Guy's and St Thomas' Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bj\u00f8rnsen","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Ueland","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H.","family":"Pripp","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. E.","family":"Tj\u00f8nnfjord","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Oslo Oslo Norway"},{"name":"Department of Haematology Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. A.","family":"Holme","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo Oslo Norway"},{"name":"Department of Haematology Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02829.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02504.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12080"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02360.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02223.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02693.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02294.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01931.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02612.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12095"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03306.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02648.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3928\/01477447-20091124-30"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACO.0b013e3283532b29"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta17100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02748.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-08-378935"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07600.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V61.1.36.36"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198109243051301"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01601.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-017988"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02332.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00912.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01451.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02028.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08854.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02253.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.04171.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-392308"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1113270"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02755.x"},{"key":"e_1_2_9_34_1","volume-title":"Baxter International Product Specification","author":"Prescribing Information"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60835-5"},{"issue":"4","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1745-6584.2005.0048.x","article-title":"Minimizing factor requirements for surgery without increased risk","volume":"10","author":"Schulman S","year":"2004","journal-title":"Haemophilia"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-2836-z"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.01.025"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-393371"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12318","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12318","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T20:59:51Z","timestamp":1716152391000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,19]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1111\/hae.12318"],"URL":"https:\/\/doi.org\/10.1111\/hae.12318","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,19]]}}}