Skip to main content
Top
Published in: Irish Journal of Medical Science (1971 -) 2/2024

Open Access 04-10-2023 | Tranexamic Acid | Original Article

A systematic review and meta-analysis assessing the use of tranexamic acid (TXA) in acute gastrointestinal bleeding

Authors: Oisín O’Donnell, Clodagh Gallagher, Matthew G. Davey, Jonathan Coulter, Mark Regan

Published in: Irish Journal of Medical Science (1971 -) | Issue 2/2024

Login to get access

Abstract

Introduction

Gastrointestinal bleeding results in significant morbidity, cost and mortality. TXA, an antifibrinolytic agent, has been proposed to reduce mortality; however, many studies report conflicting results.

Methods

The aim of the study was to perform the first systematic review and meta-analysis of RCTs to evaluate the efficacy TXA for both upper and lower gastrointestinal bleeding. This was performed per PRISMA guidelines. PubMed, EMBASE, Cochrane and Scopus databases were searched for RCTs. Dichotomous variables were pooled as risk ratios (RR) with 95% confidence intervals (CI) using the MH method with random effects modelling.

Results

Fourteen RCTs were identified with 14,338 patients and mean age of 58.4 years. 34.9% (n = 5008) were female and 65.1% (n = 9330) male. There was no significant difference in mortality between TXA and placebo (RR 0.86 95% CI (0.74 to 1.00), P: 0.05). The secondary outcomes, similarly, did not yield significant results. These included rebleeding, need for surgical intervention (RR: 0.75 95% CI (0.53, 1.07)), endoscopic intervention (RR: 0.92 95% CI (0.70, 1.22)), transfusion requirement (RR: 1.01 95% CI (0.94, 10.7)) and length of stay (RR: 0.03 95% CI (− 0.03, 0.08)). There was no increased risk of VTE, RR: 1.29 95% CI (0.53, 3.16). One trial (n = 12,009) reported an increased risk of seizure in the TXA group, RR: 1.73 95% CI (1.03–2.93).

Conclusion

TXA does not reduce mortality in patients with acute upper or lower gastrointestinal bleeding and may confer an increased risk of seizures. The authors do not recommend the use of TXA in acute gastrointestinal bleeding.
Appendix
Available only for authorised users
Literature
2.
go back to reference van Leerdam ME (2008) Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol 22(2):209–224CrossRefPubMed van Leerdam ME (2008) Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol 22(2):209–224CrossRefPubMed
3.
go back to reference Javaid T, Siddiqui N, Hasan S, Khan Z, Tabassum S, Khuder S et al (2016) The in-hospital mortality rate in gastrointestinal hemorrhage with shock: a nationwide analysis: 966. Am J Gastroenterol 111 Javaid T, Siddiqui N, Hasan S, Khan Z, Tabassum S, Khuder S et al (2016) The in-hospital mortality rate in gastrointestinal hemorrhage with shock: a nationwide analysis: 966. Am J Gastroenterol 111
4.
go back to reference Dworzynski K, Pollit V, Kelsey A et al (2012) Management of acute upper gastrointestinal bleeding: summary of NICE guidance. BMJ 344:e3412CrossRefPubMed Dworzynski K, Pollit V, Kelsey A et al (2012) Management of acute upper gastrointestinal bleeding: summary of NICE guidance. BMJ 344:e3412CrossRefPubMed
6.
go back to reference Roberts I, Shakur H, Coats T et al (2013) The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess 17(10):1–79CrossRefPubMedPubMedCentral Roberts I, Shakur H, Coats T et al (2013) The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess 17(10):1–79CrossRefPubMedPubMedCentral
7.
go back to reference Cox HT, Poller L, Thomson JM (1967) Gastric fibrinolysis. A possible aetiological link with peptic ulcer. Lancet 7503:1300–1302CrossRef Cox HT, Poller L, Thomson JM (1967) Gastric fibrinolysis. A possible aetiological link with peptic ulcer. Lancet 7503:1300–1302CrossRef
8.
go back to reference Nilsson IM, Bergentz SE, Hedner U, Kullenberg K (1975) Gastric fibrinolysis. Thromb Diath Haemorrh 34(2):409–418PubMed Nilsson IM, Bergentz SE, Hedner U, Kullenberg K (1975) Gastric fibrinolysis. Thromb Diath Haemorrh 34(2):409–418PubMed
9.
go back to reference Shakur H, Elbourne D, Gülmezoglu M et al (2010) The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 11:40CrossRefPubMedPubMedCentral Shakur H, Elbourne D, Gülmezoglu M et al (2010) The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 11:40CrossRefPubMedPubMedCentral
10.
go back to reference CRASH-3 trial collaborators (2019) 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. Lancet 394(10210):1713-1723. https://doi.org/10.1016/S0140-6736(19)32233-0. Epub 2019 Oct 14. Erratum in: Lancet. 2019 Nov 9;394(10210):1712. PMID: 31623894; PMCID: PMC6853170 CRASH-3 trial collaborators (2019) 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. Lancet 394(10210):1713-1723. https://​doi.​org/​10.​1016/​S0140-6736(19)32233-0. Epub 2019 Oct 14. Erratum in: Lancet. 2019 Nov 9;394(10210):1712. PMID: 31623894; PMCID: PMC6853170
11.
go back to reference Lin ZX, Woolf SK (2016) Safety, efficacy, and cost-effectiveness of tranexamic acid in orthopedic surgery. Orthopedics 39(2):119–130CrossRefPubMed Lin ZX, Woolf SK (2016) Safety, efficacy, and cost-effectiveness of tranexamic acid in orthopedic surgery. Orthopedics 39(2):119–130CrossRefPubMed
12.
go back to reference Roberts I, Shakur-Still H, Afolabi A et al (2021) A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT. Health Technol Assess 25:58CrossRef Roberts I, Shakur-Still H, Afolabi A et al (2021) A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT. Health Technol Assess 25:58CrossRef
13.
go back to reference Burke E, Harkins P, Ahmed I (2021) Is there a role for tranexamic acid in upper GI bleeding? A systematic review and meta-analysis. Surg Res Pract 2021:8876991PubMedPubMedCentral Burke E, Harkins P, Ahmed I (2021) Is there a role for tranexamic acid in upper GI bleeding? A systematic review and meta-analysis. Surg Res Pract 2021:8876991PubMedPubMedCentral
14.
go back to reference Kamal F, Khan MA, Lee-Smith W et al (2020) Efficacy and safety of tranexamic acid in acute upper gastrointestinal bleeding: meta-analysis of randomised controlled trials. Scand J Gastroenterol 55(12):1390–1397CrossRefPubMed Kamal F, Khan MA, Lee-Smith W et al (2020) Efficacy and safety of tranexamic acid in acute upper gastrointestinal bleeding: meta-analysis of randomised controlled trials. Scand J Gastroenterol 55(12):1390–1397CrossRefPubMed
15.
go back to reference Ng W, Jerath A, Wąsowicz M (2015) Tranexamic acid: a clinical review. Anaesthesiol Intensive Ther 47(4):339–350CrossRefPubMed Ng W, Jerath A, Wąsowicz M (2015) Tranexamic acid: a clinical review. Anaesthesiol Intensive Ther 47(4):339–350CrossRefPubMed
16.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefPubMedPubMedCentral Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefPubMedPubMedCentral
17.
go back to reference O’Donnell O, Regan M (2022) Systematic review of the use of tranexamic acid (TXA) in acute gastrointestinal bleeding. PROSPERO 2022. PROSPERO International prospective register of systematic reviews. Reference CRD42022308878 O’Donnell O, Regan M (2022) Systematic review of the use of tranexamic acid (TXA) in acute gastrointestinal bleeding. PROSPERO 2022. PROSPERO International prospective register of systematic reviews. Reference CRD42022308878
18.
go back to reference Richardson WS, Wilson MC, Nishikawa J, Hayward RS (1995) The well-built clinical question: a key to evidence-based decisions. ACP J Club 123(3):A12–A13CrossRefPubMed Richardson WS, Wilson MC, Nishikawa J, Hayward RS (1995) The well-built clinical question: a key to evidence-based decisions. ACP J Club 123(3):A12–A13CrossRefPubMed
19.
go back to reference Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898CrossRefPubMed Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898CrossRefPubMed
20.
go back to reference Bagnenko SF, Verbitskiĭ VG (2011) Antifibrinolitic therapy for the treatment of massive ulcerative gastro-intestinal bleedings. Khirurgiia (Mosk) 4:42–46 Bagnenko SF, Verbitskiĭ VG (2011) Antifibrinolitic therapy for the treatment of massive ulcerative gastro-intestinal bleedings. Khirurgiia (Mosk) 4:42–46
21.
go back to reference Barer D, Ogilvie A, Henry D et al (1983) Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding. N Engl J Med 308(26):1571–1575CrossRefPubMed Barer D, Ogilvie A, Henry D et al (1983) Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding. N Engl J Med 308(26):1571–1575CrossRefPubMed
22.
go back to reference Bashiri H, Hamzeii M, Bozorgomid A (2021) Effect of tranexamic acid on the treatment of patients with upper gastrointestinal bleeding: a double-blinded randomized controlled clinical trial. J Acute Dis 10(2):57–61CrossRef Bashiri H, Hamzeii M, Bozorgomid A (2021) Effect of tranexamic acid on the treatment of patients with upper gastrointestinal bleeding: a double-blinded randomized controlled clinical trial. J Acute Dis 10(2):57–61CrossRef
23.
go back to reference Bergqvist D, Dahlgren S, Hessman Y (1980) Local inhibition of the fibrinolytic system in patients with massive upper gastrointestinal hemorrhage. Upsala J Med Sci 85(2):173–178CrossRefPubMed Bergqvist D, Dahlgren S, Hessman Y (1980) Local inhibition of the fibrinolytic system in patients with massive upper gastrointestinal hemorrhage. Upsala J Med Sci 85(2):173–178CrossRefPubMed
25.
go back to reference Cormack F, Jouhar AJ, Chakrabarti RR, Fearnley GR (1973) Tranexamic acid in upper gastrointestinal haemorrhage. Lancet 301(7814):1207–1208CrossRef Cormack F, Jouhar AJ, Chakrabarti RR, Fearnley GR (1973) Tranexamic acid in upper gastrointestinal haemorrhage. Lancet 301(7814):1207–1208CrossRef
26.
go back to reference Engqvist A, Broström O, Feilitzen FV et al (1979) Tranexamic acid in massive haemorrhage from the upper gastrointestinal tract: a double-blind study. Scand J Gastroenterol 14(7):839–844CrossRefPubMed Engqvist A, Broström O, Feilitzen FV et al (1979) Tranexamic acid in massive haemorrhage from the upper gastrointestinal tract: a double-blind study. Scand J Gastroenterol 14(7):839–844CrossRefPubMed
27.
go back to reference Hawkey GM, Cole AT, McIntyre AS et al (2001) Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings as surrogate end points. Gut 49(3):372CrossRefPubMedPubMedCentral Hawkey GM, Cole AT, McIntyre AS et al (2001) Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings as surrogate end points. Gut 49(3):372CrossRefPubMedPubMedCentral
29.
go back to reference Karadas A, Dogan NÖ, Pinar SG et al (2020) A randomized controlled trial of the effects of local tranexamic acid on mortality, rebleeding, and recurrent endoscopy need in patients with upper gastrointestinal hemorrhage. Eur J Gastroenterol Hepatol 32(1) Karadas A, Dogan NÖ, Pinar SG et al (2020) A randomized controlled trial of the effects of local tranexamic acid on mortality, rebleeding, and recurrent endoscopy need in patients with upper gastrointestinal hemorrhage. Eur J Gastroenterol Hepatol 32(1)
30.
go back to reference Rafeey M, Shoaran M, Ghergherechi R (2016) Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: a randomised controlled trial. Afr J Paediatr Surg 13(1):9–13CrossRefPubMedPubMedCentral Rafeey M, Shoaran M, Ghergherechi R (2016) Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: a randomised controlled trial. Afr J Paediatr Surg 13(1):9–13CrossRefPubMedPubMedCentral
31.
go back to reference Smith SR, Murray D, Pockney PG et al (2018) Tranexamic acid for lower GI hemorrhage: a randomized placebo-controlled clinical trial. Dis Colon Rectum 61(1) Smith SR, Murray D, Pockney PG et al (2018) Tranexamic acid for lower GI hemorrhage: a randomized placebo-controlled clinical trial. Dis Colon Rectum 61(1)
32.
go back to reference Tavakoli N, Mokhtare M, Agah S et al (2017) Comparison of the efficacy of intravenous tranexamic acid with and without topical administration versus placebo in urgent endoscopy rate for acute gastrointestinal bleeding: a double-blind randomized controlled trial. United European Gastroenterol J 6(1):46–54CrossRefPubMedPubMedCentral Tavakoli N, Mokhtare M, Agah S et al (2017) Comparison of the efficacy of intravenous tranexamic acid with and without topical administration versus placebo in urgent endoscopy rate for acute gastrointestinal bleeding: a double-blind randomized controlled trial. United European Gastroenterol J 6(1):46–54CrossRefPubMedPubMedCentral
33.
go back to reference von Holstein CC, Eriksson SB, Källén R (1987) Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding. Br Med J (Clin Res Ed) 294(6563):7CrossRef von Holstein CC, Eriksson SB, Källén R (1987) Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding. Br Med J (Clin Res Ed) 294(6563):7CrossRef
34.
35.
go back to reference Laine L, McQuaid KR (2009) Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol 7(1):33–47; quiz 1–2CrossRefPubMed Laine L, McQuaid KR (2009) Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol 7(1):33–47; quiz 1–2CrossRefPubMed
36.
go back to reference Saidi H, Shojaie S, Ghavami Y et al (2017) Role of intra-gastric tranexamic acid in management of acute upper gastrointestinal bleeding. IIOAB J 8:76–81 Saidi H, Shojaie S, Ghavami Y et al (2017) Role of intra-gastric tranexamic acid in management of acute upper gastrointestinal bleeding. IIOAB J 8:76–81
37.
go back to reference Bennett C, Klingenberg SL, Langholz E, Gluud LL (2014) Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2014(11):Cd006640PubMedPubMedCentral Bennett C, Klingenberg SL, Langholz E, Gluud LL (2014) Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2014(11):Cd006640PubMedPubMedCentral
38.
go back to reference García-Iglesias P, Villoria A, Suarez D et al (2011) Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer. Aliment Pharmacol Ther 34(8):888–900CrossRefPubMed García-Iglesias P, Villoria A, Suarez D et al (2011) Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer. Aliment Pharmacol Ther 34(8):888–900CrossRefPubMed
39.
go back to reference Taeuber I, Weibel S, Herrmann E et al (2021) Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression. JAMA Surg 156(6):e210884CrossRefPubMedPubMedCentral Taeuber I, Weibel S, Herrmann E et al (2021) Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression. JAMA Surg 156(6):e210884CrossRefPubMedPubMedCentral
40.
go back to reference Murao S, Nakata H, Roberts I, Yamakawa K (2021) Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis. Crit Care 25(1):380CrossRefPubMedPubMedCentral Murao S, Nakata H, Roberts I, Yamakawa K (2021) Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis. Crit Care 25(1):380CrossRefPubMedPubMedCentral
41.
go back to reference Dionne JC, Oczkowski SJW, Hunt BJ et al (2022) Tranexamic acid in gastrointestinal bleeding: a systematic review and meta-analysis. Crit Care Med 50(3):e313–e319CrossRefPubMed Dionne JC, Oczkowski SJW, Hunt BJ et al (2022) Tranexamic acid in gastrointestinal bleeding: a systematic review and meta-analysis. Crit Care Med 50(3):e313–e319CrossRefPubMed
42.
go back to reference Ting KH, Shiu BH, Yang SF et al (2022) Risk of mortality among patients with gastrointestinal bleeding with early and late treatment with tranexamic acid: a population-based cohort study. J Clin Med 11(6) Ting KH, Shiu BH, Yang SF et al (2022) Risk of mortality among patients with gastrointestinal bleeding with early and late treatment with tranexamic acid: a population-based cohort study. J Clin Med 11(6)
43.
go back to reference Miyamoto Y, Ohbe H, Ishimaru M et al (2021) Effect of tranexamic acid in patients with colonic diverticular bleeding: a nationwide inpatient database study. J Gastroenterol Hepatol 36(4):999–1005CrossRefPubMed Miyamoto Y, Ohbe H, Ishimaru M et al (2021) Effect of tranexamic acid in patients with colonic diverticular bleeding: a nationwide inpatient database study. J Gastroenterol Hepatol 36(4):999–1005CrossRefPubMed
44.
go back to reference Heidet M, Amathieu R, Audureau E et al (2018) Efficacy and tolerance of early administration of tranexamic acid in patients with cirrhosis presenting with acute upper gastrointestinal bleeding: a study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (the EXARHOSE study). BMJ Open 8(8):e021943CrossRefPubMedPubMedCentral Heidet M, Amathieu R, Audureau E et al (2018) Efficacy and tolerance of early administration of tranexamic acid in patients with cirrhosis presenting with acute upper gastrointestinal bleeding: a study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (the EXARHOSE study). BMJ Open 8(8):e021943CrossRefPubMedPubMedCentral
Metadata
Title
A systematic review and meta-analysis assessing the use of tranexamic acid (TXA) in acute gastrointestinal bleeding
Authors
Oisín O’Donnell
Clodagh Gallagher
Matthew G. Davey
Jonathan Coulter
Mark Regan
Publication date
04-10-2023
Publisher
Springer International Publishing
Published in
Irish Journal of Medical Science (1971 -) / Issue 2/2024
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-023-03517-0

Other articles of this Issue 2/2024

Irish Journal of Medical Science (1971 -) 2/2024 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.