{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:57:11Z","timestamp":1784617031667,"version":"3.55.0"},"reference-count":32,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish state","award":["ALF grants"],"award-info":[{"award-number":["ALF grants"]}]},{"DOI":"10.13039\/501100023867","name":"Swedish Stroke Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023867","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,1,31]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>Reversal treatment is commonly used for managing oral anticoagulant (OAC)-associated intracranial haemorrhages. Its effects on mortality are still understudied, particularly in various subtypes of intracranial haemorrhages. This systematic review and meta-analysis aims to synthesise the available data to study the impact of reversal therapies on mortality following various OAC-associated acute intracranial haemorrhages.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods and analysis<\/jats:title>\n<jats:p>This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Protocols, and the final review will be reported in accordance with the PRISMA reporting guidelines. This systematic review and meta-analysis will include studies that assess contemporary reversal treatment in comparison to no reversal treatment, in cases of OAC-associated intracranial haemorrhage. Stratification will be performed for the types of bleeding as well as OAC at bleeding onset. Preliminary searches to determine search term inclusions were conducted in May\u2013August 2024 in the electronic databases Embase, PubMed, Scopus and Web of Science without language and publication date restrictions. Randomised controlled studies, non-randomised controlled trials, and observational studies will be considered for the final meta-analysis. Three reviewers (MT, JOS and AB) will screen titles and abstracts, and one reviewer (MT) will subsequently conduct full-text screening.<\/jats:p>\n<jats:p>Risks of bias will be assessed by MT using tools such as Risk of Bias 2, Risk Of Bias In Non-randomised Studies - of Interventions and the Newcastle-Ottawa Scale. Heterogeneity among the study results will be assessed using the I\u00b2 statistic. If appropriate, a random-effects meta-analysis model will be performed. Subgroup analyses and meta-regression (if applicable) will be performed to assess sources of heterogeneity among (1) intracranial haemorrhage types, (2) OAC drugs and (3) study types, with randomised controlled trials being the primary focus.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Ethics and dissemination<\/jats:title>\n<jats:p>Ethical approval is not needed as this project involves previously published data. We intend to publish the results in a peer-reviewed journal.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>PROSPERO registration number<\/jats:title>\n<jats:p>CRD42024556420.<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/bmjopen-2024-090357","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T04:57:22Z","timestamp":1740373042000},"page":"e090357","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Reversal treatment and clinical outcomes in acute intracranial haemorrhage associated with oral anticoagulant use: protocol of a planned systematic review and meta-analysis"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2392-5341","authenticated-orcid":false,"given":"Mattias","family":"Tallroth","sequence":"first","affiliation":[{"name":"School of Medical Sciences, \u00d6rebro University Faculty of Medicine and Health, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5091-604X","authenticated-orcid":false,"given":"Linda","family":"\u00d6stlundh","sequence":"additional","affiliation":[{"name":"\u00d6rebro University Library, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-9278","authenticated-orcid":false,"given":"Andr\u00e1s","family":"B\u00fcki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, \u00d6rebro University Faculty of Medicine and Health, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3552-9153","authenticated-orcid":false,"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"},{"name":"Unit of Integrative Epidemiology, Institute of Enviromental Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"von Euler","sequence":"additional","affiliation":[{"name":"Department of Neurology and Rehabilitation, \u00d6rebro University Faculty of Medicine and Health, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob O","family":"Str\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Neurology and Rehabilitation, \u00d6rebro University Faculty of Medicine and Health, \u00d6rebro, Sweden"},{"name":"Department of General Medicine, Whangarei Hospital, Whangarei, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"2025070104270908000_15.2.e090357.1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.013343"},{"key":"2025070104270908000_15.2.e090357.2","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2020.37438","article-title":"Clinical Characteristics and Outcomes Associated With Oral Anticoagulant Use Among Patients Hospitalized With Intracerebral Hemorrhage","volume":"4","author":"Xian","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2025070104270908000_15.2.e090357.3","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316631"},{"key":"2025070104270908000_15.2.e090357.4","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1161\/STROKEAHA.120.030930","article-title":"Prognosis of Intracerebral Hemorrhage Related to Antithrombotic Use","volume":"52","author":"Apostolaki-Hansson","year":"2021","journal-title":"Stroke"},{"key":"2025070104270908000_15.2.e090357.5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s42466-023-00256-6","article-title":"Hematoma expansion in intracerebral hemorrhage - the right target?","volume":"5","author":"Haupenthal","year":"2023","journal-title":"Neurol Res Pract"},{"key":"2025070104270908000_15.2.e090357.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707278"},{"key":"2025070104270908000_15.2.e090357.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1814051"},{"key":"2025070104270908000_15.2.e090357.8","doi-asserted-by":"crossref","first-page":"R185","DOI":"10.1186\/cc11669","article-title":"Reversal of Vitamin K Antagonist (VKA) effect in patients with severe bleeding: a French multicenter observational study (Optiplex) assessing the use of Prothrombin Complex Concentrate (PCC) in current clinical practice","volume":"16","author":"Desmettre","year":"2012","journal-title":"Crit Care"},{"key":"2025070104270908000_15.2.e090357.9","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/j.ajem.2020.05.086","article-title":"A review of guidelines on anticoagulation reversal across different clinical scenarios - Is there a general consensus?","volume":"38","author":"Milling","year":"2020","journal-title":"Am J Emerg Med"},{"key":"2025070104270908000_15.2.e090357.10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s11239-018-1667-5","article-title":"Anticoagulation reversal in vitamin K antagonist-associated intracerebral hemorrhage: a systematic review","volume":"46","author":"Ko","year":"2018","journal-title":"J Thromb Thrombolysis"},{"key":"2025070104270908000_15.2.e090357.11","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s10072-019-3726-x","article-title":"Efficacy and safety of prothrombin complex concentrate for vitamin K antagonist-associated intracranial hemorrhage: a systematic review and meta-analysis","volume":"40","author":"Pan","year":"2019","journal-title":"Neurol Sci"},{"key":"2025070104270908000_15.2.e090357.12","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2022.40145","article-title":"Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage: A Systematic Review and Meta-analysis","volume":"5","author":"Chaudhary","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2025070104270908000_15.2.e090357.13","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1111\/ene.13742","article-title":"Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis","volume":"25","author":"Katsanos","year":"2018","journal-title":"Eur J Neurol"},{"key":"2025070104270908000_15.2.e090357.14","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/ana.25134","article-title":"Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage","volume":"83","author":"Gerner","year":"2018","journal-title":"Ann Neurol"},{"key":"2025070104270908000_15.2.e090357.15","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.121.034572"},{"key":"2025070104270908000_15.2.e090357.16","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11123399","article-title":"Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study","volume":"11","author":"Rauch","year":"2022","journal-title":"J Clin Med"},{"key":"2025070104270908000_15.2.e090357.17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2313040"},{"key":"2025070104270908000_15.2.e090357.18","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2023.1212495","article-title":"Outcome after intracranial hemorrhage under dabigatran and reversal with idarucizumab versus under vitamin-K-antagonists - the RIC-ICH study","volume":"14","author":"Kuklik","year":"2023","journal-title":"Front Neurol"},{"key":"2025070104270908000_15.2.e090357.19","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2021.727403","article-title":"Dabigatran Reversal With Idarucizumab and In-Hospital Mortality in Intracranial Hemorrhage: A Systematic Review of Real-Life Data From Case Reports and Case Series","volume":"12","author":"Frol","year":"2021","journal-title":"Front Neurol"},{"key":"2025070104270908000_15.2.e090357.20","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000407"},{"key":"2025070104270908000_15.2.e090357.21","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S1474-4422(16)00110-1","article-title":"Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial","volume":"15","author":"Steiner","year":"2016","journal-title":"Lancet Neurol"},{"key":"2025070104270908000_15.2.e090357.22","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.0846"},{"key":"2025070104270908000_15.2.e090357.23","unstructured":"Riksstroke The Swedish Stroke Register . Arsrapporten-2022-preliminar.pdf. 2023. Available: https:\/\/www.riksstroke.org\/wp-content\/uploads\/2023\/09\/Arsrapporten-2022-preliminar-230919.pdf"},{"key":"2025070104270908000_15.2.e090357.24","unstructured":"The National Board of Health and Welfare . L\u00e4kemedelsf\u00f6rs\u00e4ljning i Sverige \u2013 analys och prognos 2022\u20132025, 2022. Available: https:\/\/www.socialstyrelsen.se\/globalassets\/sharepoint-dokument\/artikelkatalog\/ovrigt\/2022-4-7858.pdf [Accessed 21 Jan 2024]."},{"key":"2025070104270908000_15.2.e090357.25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/phar.2901","article-title":"Is reversal of anticoagulants necessary in neurologically intact traumatic intracranial hemorrhage?","volume":"44","author":"Powell","year":"2024","journal-title":"Pharmacotherapy"},{"key":"2025070104270908000_15.2.e090357.26","doi-asserted-by":"publisher","DOI":"10.1186\/2046-4053-4-1"},{"key":"2025070104270908000_15.2.e090357.27","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2025070104270908000_15.2.e090357.28","unstructured":"Cabells . Predatory reports. Available: https:\/\/cabells.com\/solutions\/predatory-reports [Accessed 21 Apr 2024]."},{"key":"2025070104270908000_15.2.e090357.29","unstructured":"Cochrane . Recommendations on testing for funnel plot asymmetry, Available: https:\/\/handbook-5 1.cochrane.org\/chapter_10\/10_4_3_1_recommendations_on_testing_for_funnel_plot_asymmetry.htm [Accessed 18 Nov 2024]."},{"key":"2025070104270908000_15.2.e090357.30","doi-asserted-by":"publisher","DOI":"10.1136\/bmjebm-2022-111962"},{"key":"2025070104270908000_15.2.e090357.31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709118"},{"key":"2025070104270908000_15.2.e090357.32","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.54916","article-title":"Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants","volume":"7","author":"Ip","year":"2024","journal-title":"JAMA Netw Open"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-090357","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T16:00:59Z","timestamp":1754496059000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-090357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,26]]},"published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1136\/bmjopen-2024-090357"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-090357","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]}}}