{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:17:50Z","timestamp":1784542670794,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T00:00:00Z","timestamp":1490313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Direct oral anticoagulants (DOACs) are effective and safe for prophylaxis and treatment of thromboembolic phenomena. However, managing DOACs during bleeding emergencies is challenging. A systematic review and meta\u2010analysis was conducted on studies addressing efficacy and safety of the drugs used for reversal of DOACs.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>Medline, Embase, Cochrane Library, and<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>were searched up to September 2016. Studies that examined clinical and laboratory effects of drugs used to reverse DOACs were included. Risk of bias was assessed using Newcastle\u2010Ottawa scale and Cochrane Collaboration tool. Primary and secondary outcomes assessed were reversal of clinical bleeding, clotting assays, and safety, respectively. Overall effect estimates were pooled, and clinical and statistical heterogeneity were assessed. Meta\u2010analysis was conducted using random\u2010effects model.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Four cohort studies in bleeding patients (n\u00a0=\u00a0230) and eight randomized controlled trials in healthy volunteers (n\u00a0=\u00a0381) were included, both with moderate risk of bias. Reversal of clotting assays in healthy volunteers was frequently reported, demonstrating that prothrombin complex concentrate (PCC) reversed prothrombin time (PT) and endogenous thrombin potential (ETP) substantially. For PT, pooled mean difference was 1.68 seconds (95% confidence interval [CI], \u22120.33 to 3.70 sec; p<jats:italic>\u00a0&lt;\u00a0<\/jats:italic>0.01; I<jats:sup>2<\/jats:sup>\u00a0=\u00a097%). For ETP, pooled mean difference was 2.16 seconds (95% CI, 0.57 to 3.75 sec; p\u00a0&lt;\u00a00.01; I<jats:sup>2<\/jats:sup>\u00a0=<jats:sup>\u00a0<\/jats:sup>98%). Andexanet alfa and idarucizumab both reverse clotting assays. No important safety concerns were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Clotting assays are partially reversed by PCC in healthy volunteers. Idarucizumab and andexanet alfa have solid laboratory reversal effect and potential to be clinically efficacious and safe. However, clinical evidence is still lacking for all agents.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.14096","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T12:01:12Z","timestamp":1490356872000},"page":"1834-1846","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and safety of the drugs used to reverse direct oral anticoagulants: a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"57","author":[{"given":"Luis Teodoro","family":"da Luz","sequence":"first","affiliation":[{"name":"Departments of Surgery (Sunnybrook Health Sciences Centre)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylene","family":"Marchand","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Sherbrooke Sherbrooke Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartolomeu","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Sunnybrook Health Sciences Centre)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homer","family":"Tien","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Sunnybrook Health Sciences Centre)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery","family":"Nathens","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Sunnybrook Health Sciences Centre)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakesh","family":"Shah","sequence":"additional","affiliation":[{"name":"Pediatrics (Mount Sinai Hospital), University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euv030"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/0003088-200948010-00001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.653048"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.110.937680"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009638"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310907"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-563577"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22373"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu463"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/HPC.0000000000000042"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.03.056"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303402"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-468207"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3102"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03429.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2010.02.007"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_2_8_21_1","unstructured":"WellsGA SheaB O'ConnellD et al. 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