{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:47:17Z","timestamp":1780544837604,"version":"3.54.1"},"reference-count":91,"publisher":"National Institute for Health and Care Research","issue":"58","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["11\/01\/04"],"award-info":[{"award-number":["11\/01\/04"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n Adults with significant upper or lower gastrointestinal bleeding (n<\/jats:italic>\u2009=\u200912,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo.<\/jats:p>\n <\/jats:sec>\n \n Main outcome measures<\/jats:title>\n The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 12,009 patients were allocated to receive tranexamic acid (n<\/jats:italic>\u2009=\u20095994, 49.9%) or the matching placebo (n<\/jats:italic>\u2009=\u20096015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding.<\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes.<\/jats:p>\n <\/jats:sec>\n \n Limitations<\/jats:title>\n Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment<\/jats:italic>; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/hta25580","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T14:26:27Z","timestamp":1634653587000},"page":"1-86","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT"],"prefix":"10.3310","volume":"25","clinical-trial-number":[{"clinical-trial-number":"isrctn11225767","registry":"10.18810\/isrctn","type":"results"},{"clinical-trial-number":"nct01658124","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"2012-003192-19","registry":"10.18810\/euctr","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-6054","authenticated-orcid":true,"given":"Ian","family":"Roberts","sequence":"first","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6511-109X","authenticated-orcid":true,"given":"Haleema","family":"Shakur-Still","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6195-6669","authenticated-orcid":true,"given":"Adefemi","family":"Afolabi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University College Hospital Ibadan, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-3998","authenticated-orcid":true,"given":"Adegboyega","family":"Akere","sequence":"additional","affiliation":[{"name":"Department of Medicine, University College Hospital Ibadan, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1405-9391","authenticated-orcid":true,"given":"Monica","family":"Arribas","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-5534","authenticated-orcid":true,"given":"Emma","family":"Austin","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-8660","authenticated-orcid":true,"given":"Kiran","family":"Bal","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-8402","authenticated-orcid":true,"given":"Nuha","family":"Bazeer","sequence":"additional","affiliation":[{"name":"Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK"},{"name":"Department of Health Policy, London School of Economics and Political Science, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2530-9608","authenticated-orcid":true,"given":"Danielle","family":"Beaumont","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-5994","authenticated-orcid":true,"given":"Amy","family":"Brenner","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-2092","authenticated-orcid":true,"given":"Laura","family":"Carrington","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5428-3988","authenticated-orcid":true,"given":"Rizwana","family":"Chaudhri","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Rawalpindi Medical University, Rawalpindi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2736-2784","authenticated-orcid":true,"given":"Timothy","family":"Coats","sequence":"additional","affiliation":[{"name":"Emergency Department, Leicester Royal Infirmary, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0720-3612","authenticated-orcid":true,"given":"Ian","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Alcohol Research, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-9958","authenticated-orcid":true,"given":"Kenneth","family":"Halligan","sequence":"additional","affiliation":[{"name":"Patient representative, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5342-0530","authenticated-orcid":true,"given":"Irshad","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Medicine, King Edward Medical University, Mayo Hospital, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1092-0033","authenticated-orcid":true,"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Western University and London Health Sciences Centre, London, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-0552","authenticated-orcid":true,"given":"Kiran","family":"Javaid","sequence":"additional","affiliation":[{"name":"Rawalpindi Medical University \u2013 Pakistan National Coordinating Centre (RMU-PNCC), Rawalpindi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2782-9508","authenticated-orcid":true,"given":"Aasia","family":"Kayani","sequence":"additional","affiliation":[{"name":"Rawalpindi Medical University \u2013 Pakistan National Coordinating Centre (RMU-PNCC), Rawalpindi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3503-7140","authenticated-orcid":true,"given":"Ton","family":"Lisman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-5859","authenticated-orcid":true,"given":"Raoul","family":"Mansukhani","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1850-1463","authenticated-orcid":true,"given":"Alec","family":"Miners","sequence":"additional","affiliation":[{"name":"Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9338-962X","authenticated-orcid":true,"given":"Muttiullah","family":"Mutti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-5330","authenticated-orcid":true,"given":"Muhammad Arif","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Medical Unit III, Services Institute of Medical Sciences, Services Hospital Gastrointestinal, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6452-6763","authenticated-orcid":true,"given":"Richard","family":"Pollok","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, St George\u2019s Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-4823","authenticated-orcid":true,"given":"Danielle","family":"Prowse","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-4110","authenticated-orcid":true,"given":"Jonathan","family":"Simmons","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Royal Berkshire Hospital, Reading, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7414-4950","authenticated-orcid":true,"given":"Simon","family":"Stanworth","sequence":"additional","affiliation":[{"name":"Transfusion Medicine, NHS Blood and Transplant (NHSBT), John Radcliffe Hospital, Oxford, UK"},{"name":"Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, UK"},{"name":"Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-2370","authenticated-orcid":true,"given":"Andrew","family":"Veitch","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, New Cross Hospital, Wolverhampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-387X","authenticated-orcid":true,"given":"Jack","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2021,10]]},"reference":[{"key":"key20211019092525773_ref1-bib1","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/1745-6215-15-450","article-title":"HALT-IT \u2013 tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial","volume":"15","author":"Roberts","year":"2014","journal-title":"Trials"},{"key":"key20211019092525773_ref1-bib2","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1186\/s13063-019-3561-7","article-title":"Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial","volume":"20","author":"Brenner","year":"2019","journal-title":"Trials"},{"key":"key20211019092525773_ref1-bib3","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1016\/S0140-6736(20)30848-5","article-title":"Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial","volume":"395","author":"HALT-IT Trial Collaborators","year":"2020","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.bpg.2007.10.011","article-title":"Epidemiology of acute upper gastrointestinal bleeding","volume":"22","author":"van Leerdam","year":"2008","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"key20211019092525773_ref1-bib5","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1136\/gut.2010.228437","article-title":"Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit","volume":"60","author":"Hearnshaw","year":"2011","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib6","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1136\/gutjnl-2016-313428","article-title":"Acute lower GI bleeding in the UK: patient characteristics, interventions and outcomes in the first nationwide audit","volume":"67","author":"Oakland","year":"2018","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib7","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1111\/j.1365-2036.2005.02485.x","article-title":"Review article: the management of lower gastrointestinal bleeding","volume":"21","author":"Farrell","year":"2005","journal-title":"Aliment Pharmacol Ther"},{"key":"key20211019092525773_ref1-bib8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/gut.2006.117598","article-title":"Gastroenterology services in the UK. The burden of disease, and the organisation and delivery of services for gastrointestinal and liver disorders: a review of the evidence","volume":"56","author":"Williams","year":"2007","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib9","first-page":"419","article-title":"Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study","volume":"92","author":"Longstreth","year":"1997","journal-title":"Am J Gastroenterol"},{"key":"key20211019092525773_ref1-bib10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/j.1365-2036.2010.04495.x","article-title":"Hospitalized incidence and case fatality for upper gastrointestinal bleeding from 1999 to 2007: a record linkage study","volume":"33","author":"Button","year":"2011","journal-title":"Aliment Pharmacol Ther"},{"key":"key20211019092525773_ref1-bib11","doi-asserted-by":"publisher","first-page":"g4606","DOI":"10.1136\/bmj.g4606","article-title":"Predicting risk of upper gastrointestinal bleed and intracranial bleed with anticoagulants: cohort study to derive and validate the QBleed scores","volume":"349","author":"Hippisley-Cox","year":"2014","journal-title":"BMJ"},{"key":"key20211019092525773_ref1-bib12","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1097\/01.mcg.0000248004.73075.ad","article-title":"Changing trends in the epidemiology and clinical outcome of acute upper gastrointestinal bleeding in a defined geographical area in Greece","volume":"42","author":"Theocharis","year":"2008","journal-title":"J Clin Gastroenterol"},{"key":"key20211019092525773_ref1-bib13","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1097\/00042737-200012020-00007","article-title":"Epidemiology and course of acute upper gastro-intestinal haemorrhage in four French geographical areas","volume":"12","author":"Czernichow","year":"2000","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"key20211019092525773_ref1-bib14","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1111\/j.1572-0241.2003.07517.x","article-title":"Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993\/1994 and 2000","volume":"98","author":"van Leerdam","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"key20211019092525773_ref1-bib15","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3109\/00365521.2012.763174","article-title":"Upper gastrointestinal bleeding: incidence, etiology and outcomes in a population-based setting","volume":"48","author":"Hreinsson","year":"2013","journal-title":"Scand J Gastroenterol"},{"key":"key20211019092525773_ref1-bib16","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1038\/ajg.2012.168","article-title":"Trends for incidence of hospitalization and death due to GI complications in the United States from 2001 to 2009","volume":"107","author":"Laine","year":"2012","journal-title":"Am J Gastroenterol"},{"key":"key20211019092525773_ref1-bib17","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1007\/s10620-017-4882-6","article-title":"Changing Epidemiology of upper gastrointestinal hemorrhage in the last decade: a nationwide analysis","volume":"63","author":"Wuerth","year":"2018","journal-title":"Dig Dis Sci"},{"key":"key20211019092525773_ref1-bib18","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.gie.2014.09.027","article-title":"The in-hospital mortality rate for upper GI hemorrhage has decreased over 2 decades in the United States: a nationwide analysis","volume":"81","author":"Abougergi","year":"2015","journal-title":"Gastrointest Endosc"},{"key":"key20211019092525773_ref1-bib19","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1097\/00042737-200506000-00008","article-title":"Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study","volume":"17","author":"Di Fiore","year":"2005","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"key20211019092525773_ref1-bib20","doi-asserted-by":"publisher","first-page":"253","DOI":"10.4103\/1319-3767.70608","article-title":"Etiology and outcome of patients with upper gastrointestinal bleeding: a study from South of Iran","volume":"16","author":"Kaviani","year":"2010","journal-title":"Saudi J Gastroenterol"},{"key":"key20211019092525773_ref1-bib21","doi-asserted-by":"publisher","first-page":"29","DOI":"10.4103\/njss.njss_7_15","article-title":"Etiology of upper gastrointestinal bleeding in the University of Benin Teaching Hospital, South-Southern Nigeria","volume":"26","author":"Ugiagbe","year":"2016","journal-title":"Niger J Surg Sci"},{"key":"key20211019092525773_ref1-bib22","first-page":"425","article-title":"Clinical epidemiological characteristics and change trend of upper gastrointestinal bleeding over the past 15 years","volume":"20","author":"Wang","year":"2017","journal-title":"Zhonghua Wei Chang Wai Ke Za Zhi"},{"key":"key20211019092525773_ref1-bib23","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1111\/jgh.13617","article-title":"Etiology and outcome in patients with upper gastrointestinal bleeding: study on 4747 patients in the central region of Iran","volume":"32","author":"Minakari","year":"2017","journal-title":"J Gastroenterol Hepatol"},{"key":"key20211019092525773_ref1-bib24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1097\/MCG.0b013e318297fb40","article-title":"Causes of bleeding and outcomes in patients hospitalized with upper gastrointestinal bleeding","volume":"48","author":"Kim","year":"2014","journal-title":"J Clin Gastroenterol"},{"key":"key20211019092525773_ref1-bib25","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nrgastro.2009.167","article-title":"Diagnosis and management of lower gastrointestinal bleeding","volume":"6","author":"Barnert","year":"2009","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"key20211019092525773_ref1-bib26","doi-asserted-by":"publisher","DOI":"10.4172\/2161-069x.1000235","article-title":"Determinants and outcome of acute upper gastrointestinal bleeding in Yemen","volume":"4","author":"Hassan Al-Dholea","year":"2014","journal-title":"J Gastrointest Dig Syst"},{"key":"key20211019092525773_ref1-bib27","first-page":"455","article-title":"Causes and outcome of upper gastrointestinal bleeding in Emergency Endoscopy Unit of Ain Shams University Hospital","volume":"41","author":"Elwakil","year":"2011","journal-title":"J Egypt Soc Parasitol"},{"key":"key20211019092525773_ref1-bib28","doi-asserted-by":"publisher","first-page":"518","DOI":"10.4314\/ahs.v12i4.19","article-title":"Endoscopic findings in upper gastrointestinal bleeding patients at Lacor hospital, northern Uganda","volume":"12","author":"Alema","year":"2012","journal-title":"Afr Health Sci"},{"key":"key20211019092525773_ref1-bib29","first-page":"4539","article-title":"Risk factors for upper gastrointestinal bleeding requiring hospitalization","volume":"9","author":"Jiang","year":"2016","journal-title":"Int J Clin Exp Med"},{"key":"key20211019092525773_ref1-bib30","doi-asserted-by":"publisher","first-page":"34","DOI":"10.4103\/1319-3767.91737","article-title":"Clinical outcome of acute upper gastrointestinal hemorrhage among patients admitted to a government hospital in Egypt","volume":"18","author":"Gado","year":"2012","journal-title":"Saudi J Gastroenterol"},{"key":"key20211019092525773_ref1-bib31","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1590\/S0004-28032002000200002","article-title":"Upper gastrointestinal bleeding in a Brazilian hospital: a retrospective study of endoscopic records","volume":"39","author":"Zaltman","year":"2002","journal-title":"Arq Gastroenterol"},{"key":"key20211019092525773_ref1-bib32","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s12876-015-0353-8","article-title":"Trends in upper gastrointestinal diagnosis over four decades in Lusaka, Zambia: a retrospective analysis of endoscopic findings","volume":"15","author":"Kayamba","year":"2015","journal-title":"BMC Gastroenterol"},{"key":"key20211019092525773_ref1-bib33","first-page":"410","article-title":"Frequency of different causes of upper gastrointestinal bleeding using endoscopic procedure at a tertiary care hospital","volume":"64","author":"Sher","year":"2014","journal-title":"Pak Armed Forces Med J"},{"key":"key20211019092525773_ref1-bib34","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0001-706X(03)00029-9","article-title":"Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa","volume":"86","author":"van der Werf","year":"2003","journal-title":"Acta Trop"},{"key":"key20211019092525773_ref1-bib35","volume-title":"UK Comparative Audit of Upper Gastrointestinal Bleeding and the Use of Blood","author":"British Society of Gastroenterology","year":"2007"},{"key":"key20211019092525773_ref1-bib36","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1111\/j.1365-2036.2011.04651.x","article-title":"Clinical predictors of poor outcomes among patients with nonvariceal upper gastrointestinal bleeding in Europe","volume":"33","author":"Lanas","year":"2011","journal-title":"Aliment Pharmacol Ther"},{"key":"key20211019092525773_ref1-bib37","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1136\/gut.38.3.316","article-title":"Risk assessment after acute upper gastrointestinal haemorrhage","volume":"38","author":"Rockall","year":"1996","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib38","doi-asserted-by":"publisher","first-page":"e49507","DOI":"10.1371\/journal.pone.0049507","article-title":"Prognosis following upper gastrointestinal bleeding","volume":"7","author":"Roberts","year":"2012","journal-title":"PLOS ONE"},{"key":"key20211019092525773_ref1-bib39","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1038\/ajg.2014.263","article-title":"Poor outcomes in hospitalized patients with gastrointestinal bleeding: impact of baseline risk, bleeding severity, and process of care","volume":"109","author":"Jairath","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"key20211019092525773_ref1-bib40","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.3346\/jkms.2016.31.10.1611","article-title":"The clinical outcomes of lower gastrointestinal bleeding are not better than those of upper gastrointestinal bleeding","volume":"31","author":"Kwak","year":"2016","journal-title":"J Korean Med Sci"},{"key":"key20211019092525773_ref1-bib41","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1136\/gut.35.6.746","article-title":"Bleeding peptic ulcer \u2013 risk factors for rebleeding and sequential changes in endoscopic findings","volume":"35","author":"Hsu","year":"1994","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib42","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1136\/bmj.1.5739.26","article-title":"Factors predisposing to recurrent haemorrhage after acute gastrointestinal bleeding","volume":"1","author":"Northfield","year":"1971","journal-title":"Br Med J"},{"key":"key20211019092525773_ref1-bib43","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/S0016-5085(82)80264-3","article-title":"Variceal hemorrhage: a critical evaluation of survival analysis","volume":"82","author":"Smith","year":"1982","journal-title":"Gastroenterology"},{"key":"key20211019092525773_ref1-bib44","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1056\/NEJM200008033430501","article-title":"Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers","volume":"343","author":"Lau","year":"2000","journal-title":"N Engl J Med"},{"key":"key20211019092525773_ref1-bib45","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1136\/gutjnl-2011-300019","article-title":"Improving outcomes from acute upper gastrointestinal bleeding","volume":"61","author":"Jairath","year":"2012","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib46","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1136\/bmj.311.6999.222","article-title":"Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage","volume":"311","author":"Rockall","year":"1995","journal-title":"BMJ"},{"key":"key20211019092525773_ref1-bib47","unstructured":"National Institute for Health and Care Excellence (NICE) (UK). Acute Upper Gastrointestinal Bleeding in Over 16s: Management. London: NICE; 2016. URL: www.nice.org.uk\/guidance\/cg141 (accessed 13 October 2020)."},{"key":"key20211019092525773_ref1-bib48","volume-title":"Results from a National Audit National Comparative Audit of Lower Gastrointestinal Bleeding and the Use of Blood","author":"National Comparative Audit of Blood Transfusion","year":"2016"},{"key":"key20211019092525773_ref1-bib49","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1136\/gutjnl-2018-317807","article-title":"Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology","volume":"68","author":"Oakland","year":"2019","journal-title":"Gut"},{"key":"key20211019092525773_ref1-bib50","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1136\/jcp.33.Suppl_14.35","article-title":"Basis of antifibrinolytic therapy","volume":"14","author":"Prentice","year":"1980","journal-title":"J Clin Pathol Suppl"},{"key":"key20211019092525773_ref1-bib51","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/0140-6736(93)90278-O","article-title":"Association of fibrinolytic tests with outcome of acute upper-gastrointestinal-tract bleeding","volume":"341","author":"al-Mohana","year":"1993","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib52","first-page":"664","article-title":"Evidence for a relationship between fibrinolysis and haematemesis","volume":"24","author":"Poller","year":"1973","journal-title":"Br J Haematol"},{"key":"key20211019092525773_ref1-bib53","doi-asserted-by":"publisher","first-page":"e3054","DOI":"10.1136\/bmj.e3054","article-title":"Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis","volume":"344","author":"Ker","year":"2012","journal-title":"BMJ"},{"key":"key20211019092525773_ref1-bib54","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0140-6736(10)60835-5","article-title":"Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial","volume":"376","author":"The CRASH-2 Trial Collaborators","year":"2010","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib55","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1016\/S0140-6736(17)30638-4","article-title":"Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial","volume":"389","author":"The WOMAN Trial Collaborators","year":"2017","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib56","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1056\/NEJMoa1606424","article-title":"Tranexamic acid in patients undergoing coronary-artery surgery","volume":"376","author":"Myles","year":"2017","journal-title":"N Engl J Med"},{"key":"key20211019092525773_ref1-bib57","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1016\/S0140-6736(19)32233-0","article-title":"Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial","volume":"394","author":"The CRASH-3 Trial Collaborators","year":"2019","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib58","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/S0140-6736(11)60278-X","article-title":"The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial","volume":"377","author":"The CRASH-2 Trial Collaborators","year":"2011","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib59","doi-asserted-by":"publisher","first-page":"e18987","DOI":"10.1371\/journal.pone.0018987","article-title":"Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial","volume":"6","author":"Guerriero","year":"2011","journal-title":"PLOS ONE"},{"key":"key20211019092525773_ref1-bib60","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006640.pub3","article-title":"Tranexamic acid for upper gastrointestinal bleeding","volume":"11","author":"Bennett","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"key20211019092525773_ref1-bib61","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1471-230X-9-41","article-title":"Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use","volume":"9","author":"Straube","year":"2009","journal-title":"BMC Gastroenterol"},{"key":"key20211019092525773_ref1-bib62","volume-title":"Cyklokapron Tablets \u2013 Summary of Product Characteristics (SmPC)","author":"Electronic medicines compendium (emc)"},{"key":"key20211019092525773_ref1-bib63","volume-title":"Guideline for Good Clinical Practice E6(R2)","author":"Committee for Human Medicinal Products","year":"2016"},{"key":"key20211019092525773_ref1-bib64","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"key":"key20211019092525773_ref1-bib65","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001886.pub3","article-title":"Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion","volume":"1","author":"Henry","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"key20211019092525773_ref1-bib66","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1097\/00000542-199502000-00009","article-title":"The dose-response relationship of tranexamic acid","volume":"82","author":"Horrow","year":"1995","journal-title":"Anesthesiology"},{"key":"key20211019092525773_ref1-bib67","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1186\/s13063-018-2900-4","article-title":"Outcome measures in clinical trials of treatments for acute severe haemorrhage","volume":"19","author":"Brenner","year":"2018","journal-title":"Trials"},{"key":"key20211019092525773_ref1-bib68","volume-title":"Guide to the Methods of Technology Appraisal 2013","author":"National Institute for Health and Care Excellence"},{"key":"key20211019092525773_ref1-bib69","doi-asserted-by":"publisher","first-page":"e002716","DOI":"10.1136\/bmjgh-2020-002716","article-title":"Cost-effectiveness analysis of tranexamic acid for the treatment of traumatic brain injury, based on the results of the CRASH-3 randomised trial: a decision modelling approach","volume":"5","author":"Williams","year":"2020","journal-title":"BMJ Glob Health"},{"key":"key20211019092525773_ref1-bib70","volume-title":"National Life Tables, UK: 2016 to 2018","author":"Morgan","year":"2019"},{"key":"key20211019092525773_ref1-bib71","doi-asserted-by":"publisher","first-page":"e1001437","DOI":"10.1371\/journal.pmed.1001437","article-title":"Excess long-term mortality following non-variceal upper gastrointestinal bleeding: a population-based cohort study","volume":"10","author":"Crooks","year":"2013","journal-title":"PLOS Med"},{"key":"key20211019092525773_ref1-bib72","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0140-6736(14)61999-1","article-title":"Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial","volume":"386","author":"Jairath","year":"2015","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib73","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","article-title":"EuroQol \u2013 a new facility for the measurement of health-related quality of life","volume":"16","author":"The EuroQol Group","year":"1990","journal-title":"Health Policy"},{"key":"key20211019092525773_ref1-bib74","doi-asserted-by":"publisher","first-page":"e007230","DOI":"10.1136\/bmjopen-2014-007230","article-title":"Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial","volume":"5","author":"Campbell","year":"2015","journal-title":"BMJ Open"},{"key":"key20211019092525773_ref1-bib75","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1001\/jama.1963.03060120024016","article-title":"Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function","volume":"185","author":"Katz","year":"1963","journal-title":"JAMA"},{"key":"key20211019092525773_ref1-bib76","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1136\/bmj.316.7133.736","article-title":"Variations in population health status: results from a United Kingdom national questionnaire survey","volume":"316","author":"Kind","year":"1998","journal-title":"BMJ"},{"key":"key20211019092525773_ref1-bib77","unstructured":"Joint Formulary Committee. British National Formulary. 76th ed. London: BMJ Group and Pharmaceutical Press; 2019."},{"key":"key20211019092525773_ref1-bib78","volume-title":"Unit Costs of Health and Social Care 2018","author":"Curtis","year":"2018"},{"key":"key20211019092525773_ref1-bib79","doi-asserted-by":"publisher","first-page":"e222","DOI":"10.1016\/S2214-109X(17)30467-9","article-title":"Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial","volume":"6","author":"Li","year":"2018","journal-title":"Lancet Glob Health"},{"key":"key20211019092525773_ref1-bib80","volume-title":"National Schedule of Reference Costs 2017\/18","author":"NHS Improvement"},{"key":"key20211019092525773_ref1-bib81","volume-title":"NHS Blood and Transplant Price List 2018\/2019","author":"NHS Blood and Transplant"},{"key":"key20211019092525773_ref1-bib82","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2217\/fca-2019-0033","article-title":"Costs of gastrointestinal bleeding events in atrial fibrillation: a UK Clinical Practice Research Datalink study","volume":"15","author":"Ramagopalan","year":"2019","journal-title":"Future Cardiol"},{"key":"key20211019092525773_ref1-bib83","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1136\/emermed-2019-209181","article-title":"Biological mechanisms and individual variation in fibrinolysis after major trauma","volume":"37","author":"Coats","year":"2020","journal-title":"Emerg Med J"},{"key":"key20211019092525773_ref1-bib84","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12884-018-1794-1","article-title":"Haematological and fibrinolytic status of Nigerian women with post-partum haemorrhage","volume":"18","author":"Roberts","year":"2018","journal-title":"BMC Pregnancy Childbirth"},{"key":"key20211019092525773_ref1-bib85","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1002\/hep.30915","article-title":"Mixed fibrinolytic phenotypes in decompensated cirrhosis and acute-on-chronic liver failure with hypofibrinolysis in those with complications and poor survival","volume":"71","author":"Blasi","year":"2020","journal-title":"Hepatology"},{"key":"key20211019092525773_ref1-bib86","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1055\/s-0036-1585081","article-title":"Decreased plasma fibrinolytic potential as a risk for venous and arterial thrombosis","volume":"43","author":"Lisman","year":"2017","journal-title":"Semin Thromb Hemost"},{"key":"key20211019092525773_ref1-bib87","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006640.pub2","article-title":"Tranexamic acid for upper gastrointestinal bleeding","volume":"1","author":"Gluud","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"key20211019092525773_ref1-bib88","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/ana.24558","article-title":"Tranexamic acid-associated seizures: causes and treatment","volume":"79","author":"Lecker","year":"2016","journal-title":"Ann Neurol"},{"key":"key20211019092525773_ref1-bib89","doi-asserted-by":"publisher","first-page":"i6432","DOI":"10.1136\/bmj.i6432","article-title":"Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study","volume":"356","author":"Stanley","year":"2017","journal-title":"BMJ"},{"key":"key20211019092525773_ref1-bib90","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/S0140-6736(15)00489-4","article-title":"How systematic reviews cause research waste","volume":"386","author":"Roberts","year":"2015","journal-title":"Lancet"},{"key":"key20211019092525773_ref1-bib91","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1017\/S0266462302000624","article-title":"The typical Cochrane review: how many trials? How many participants?","volume":"18","author":"Mallett","year":"2002","journal-title":"Int J Technol Asses Health Care"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2037777","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/hta25580\/hta25580.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2037777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T15:38:34Z","timestamp":1692113914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/hta25580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":91,"journal-issue":{"issue":"58","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["10.3310\/hta25580"],"URL":"https:\/\/doi.org\/10.3310\/hta25580","relation":{},"ISSN":["1366-5278","2046-4924"],"issn-type":[{"value":"1366-5278","type":"print"},{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"11-2012","name":"contractual_start_date","label":"Contractual start date","group":{"name":"article_history","label":"Article History"}},{"value":"10-2020","name":"editorial_review_begun","label":"Editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"4-2021","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}