Update: What is the Role of Tranexamic Acid in Patients with Acute Gastrointestinal Bleeding?

Introduction
In December 2022, the UIC Drug Information Group reviewed the literature related to the use of tranexamic acid for the treatment of acute gastrointestinal (GI) bleeding.1 The initial review can be accessed here. The purpose of this FAQ is to summarize data on the use of tranexamic acid (TXA) for acute GI bleeding that have been published since the prior review.

Guidelines
Updated 2023 guidelines published by the American College of Gastroenterology (ACG) for the management of acute lower GI bleeding (LGIB) now address the role of antifibrinolytic agents in lower GI bleeds, and provide a strong recommendation based on moderate-quality evidence against the use of antifibrinolytics such as TXA for acute LGIB.2 The ACG bases this new recommendation on studies that have shown either no differences in mortality or no differences in the reduction of hemoglobin (Hgb) levels, transfusion rates or volumes between patients receiving oral or intravenous (IV) TXA versus placebo therapy. The 2021 ACG guideline, which focuses on upper GI and ulcer bleeding, has not been updated since the last literature review.3 The 2021 guideline primarily focuses on endoscopic and invasive interventions for the management of GI bleeding and does not address the use of TXA.

Summary of New Evidence
Several new meta-analyses and clinical studies on the use of TXA in acute GI bleeding are summarized in the Table.4-10 Two meta-analyses concluded that TXA was associated with a mortality reduction when used for the treatment of upper GI bleeding (UGIB), and either no mortality benefit when used for LGIB, or a mortality increase.4,5 The meta-analyses conducted by Calderon Martinez and colleagues found that TXA was associated with a 28% mortality reduction (risk ratio [RR], 0.72; 95% confidence interval [CI], 0.59 to 0.87) when used for UGIB, while O’Donnell and colleagues demonstrated a 15% reduction (RR, 0.85; 95% CI, 0.72 to 0.99).4,5 When TXA was used for the acute treatment of LGIB, however, Calderon Martinez and colleagues found that the risk of mortality was increased by 67% (RR, 1.67; 95% CI, 1.44 to 1.93).4 Both meta-analyses found no difference in the need for surgical intervention when TXA was used versus placebo, but came to different conclusions about the risk of rebleeding.4,5 Although Calderon Martinez and colleagues found that TXA significantly reduced the risk of rebleeding, (RR, 0.81; 95% CI, 0.87 to 0.97), when 2 large studies were excluded from the analysis (one conducted by Kumar and colleagues summarized in the Table), the smaller remaining trials lacked statistical power to demonstrate a difference in risk.4,6 Additionally, a smaller meta-analysis of studies found that TXA with acid suppression in UGIB reduced the risk of rebleeding (RR, 0.63; 95% CI, 0.41 to 0.96) and the units of blood transfused (mean difference [MD], -1.08, 95% CI, -1.44 to -0.71) compared to acid suppression alone.7 TXA plus acid suppression also reduced the need for salvage therapy (RR, 0.28; 95% CI, 0.12 to 0.64) compared to acid suppression alone, but no difference was found in mortality or the need for transfusion between groups.

A large, propensity-matched cohort study of medical claims data from over 2 million patients with hematemesis or melena who received TXA within 7 days of their UGIB diagnosis focused on assessing the risk of cardiac and thromboembolic events with the use of TXA.8 Following propensity-score matching to adjust for baseline differences in populations, TXA was shown to increase the risk of myocardial infarction (MI) (OR [odds ratio], 1.4; 95% CI, 1.2 to 1.7), cerebrovascular accident (CVA; OR, 1.6; 95% CI, 1.3 to 1.9), pulmonary embolism (PE; OR, 1.8; 95% CI, 1.5 to 2.3), and deep venous thrombosis (DVT; OR, 2.1; 95% CI, 1.28 to 2.5). After excluding patients from the analysis who had a prior reported cardiovascular event, the risk of MI, CVA, PE, and DVT remained significantly increased in patients who received TXA for UGIB versus those who did not.

Two recent randomized controlled trials (RCTs) and one retrospective study have also been published since the last literature review and guideline update.6,9,10 In the small RCT (N=81) conducted by Moscovici and colleagues, no difference in blood requirements or the units of packed red blood cells (pRBCs) was demonstrated in patients with LGIB who received TXA compared to placebo.9 In the study by Kumar and colleagues (included in the meta-analysis by Calderon Martinez and colleagues) of adults with Child-Pugh class B or C liver disease and UGIB, administration of TXA significantly reduced the failure to control bleeding by day 5 and failure to prevent rebleeding after day 5 to 6 weeks, although it had no impact on mortality.6 Additionally, in the retrospective study conducted by Bai and colleagues, a greater proportion of patients with gastric cancer and UGIB achieved successful hemostasis with TXA and esomeprazole (90.36%) versus esomeprazole alone (78.82%; p=0.003).10 Rates of secondary bleeding, thrombus formation, and digestive tract perforation were also less common with TXA versus esomeprazole alone.

Table. Newer evidence of TXA for Acute GI bleeding.4-10
Study design
Subjects		InterventionsFindings
Meta-analyses
Calderon Martinez et al 20254

SR/MA of 23 studies published between 1973 and 2024		N=2,061,263 patients of all ages with acute GI bleedingTXA PO, IV, or NGT (not all doses specified)

Placebo
  • Rates of rebleeding were reduced with TXA (RR, 0.81; 95% CI, 0.87 to 0.97).
  • TXA via PO and IV routes associated with a mortality reduction (RR, 0.56; 95% CI, 0.35 to 0.89).
  • TXA associated with mortality reduction in UGIB (RR, 0.72; 95% CI, 0.59 to 0.87) and mortality increase in LGIB (RR, 1.67; 95% CI, 1.44 to 1.93).
  • No differences in the need for transfusion, thrombotic events, or need for surgical intervention (NS).
  • The rate of thrombotic events did not increase with TXA (NS).
Kan et al 20257

SR/MA of 6 RCTs published between 1987 and 2023		N=709 adults with confirmed UGIB receiving acid suppressive therapyTXA 1 to 2 g PO, 1 g IV, or 1.25 g topical (duration not reported)

All patients received some form of acid suppression (PPI, antacid, or not reported)
  • TXA + acid suppression reduced the risk of rebleeding compared to acid suppression alone (RR, 0.63; 95% CI, 0.41 to 0.96).
  • TXA + acid suppression reduced the units of blood transfused compared to acid suppression alone (MD, -1.08, 95% CI, -1.44 to -0.71).
  • TXA + acid suppression reduced the need for salvage therapy compared to acid suppression alone (RR, 0.28; 95% CI, 0.12 to 0.64).
  • No difference in mortality or the need for transfusion between groups (NS).
O’Donnell et al 20245

14 RCTs published between 1973 and 2021		N=14,338 adults with UGIB or LGIBTXA 1 g to 6 g per day IV or PO for 1 to 7 days and/or 1 to 2 g via NGT once, or 12 g per day for 2 days

1 study: TXA 30 mg/kg per day IV or PO for 3 days

Placebo
  • No difference in mortality in patients who received TXA vs placebo (NS).
    • Subgroup analyses found no difference in patients with LGIB (NS), but a mortality benefit was shown in UGIB with TXA vs placebo (RR, 0.85; 95% CI, 0.72 to 0.99).
  • No difference in the risk of rebleeding, rate of arterial thrombotic events, need for surgical intervention, endoscopic intervention, transfusion requirement, or LOS in patients who received TXA vs none (NS).
  • One trial reported an increased risk of seizure with TXA (RR, 1.73; 95% CI, 1.03 to 2.93).
Clinical studies
Moscovici et al 20249

DB, SC, RCT		N=81 adults with LGIBTXA 1 g every 8 hours IV

Placebo
  • No difference in blood requirements in those receiving TXA versus placebo (NS).
  • No difference in the amount of pRBC units in those receiving TXA versus placebo (NS).
Bai et al 202410

Retrospective study		N=168 adults with gastric cancer and acute UGIBTXA 1 g twice daily IV + esomeprazole 80 mg IV, followed by 8 mg/hour

Esomeprazole 80 mg IV, followed by 8 mg/hour
  • More patients achieved successful hemostasis with TXA vs esomeprazole alone (90.36% vs 78.82%, respectively; p=0.003).
  • Secondary bleeding rates were reduced with TXA vs esomeprazole alone (16.87% vs 15.28%, respectively; p=0.002).
  • The thrombus formation rate was lower with TXA vs esomeprazole alone (68.67% vs 52.94%, respectively; p=0.003)
  • Digestive tract perforation was less common with TXA vs esomeprazole alone (0% vs 3.53%, respectively; p=0.035).
Fowler et al 20248

Retrospective matched cohort study of patients from 2003 to 2023		N=2,016,763 patients with hematemesis or melenaTXA given within 7 days of UGIB diagnosis
  • Following PSM, TXA vs no TXA, there was an increased risk of:
    • MI (OR, 1.4; 95% CI, 1.2 to 1.7)
    • CVA (OR, 1.6; 95% CI, 1.3 to 1.9)
    • PE (OR, 1.8; 95% CI, 1.5 to 2.3)
    • DVT (OR, 2.1; 95% CI, 1.28 to 2.5)
  • After excluding patients with a prior event, all outcomes were still significantly increased with TXA vs not:
    • MI (OR, 1.9; 95% CI, 1.3 to 2.7)
    • CVA (OR, 2.4; 95% CI, 1.5 to 3.6)
    • PE (OR, 4; 95% CI, 2.5 to 6.5)
    • DVT (OR, 2.8; 95% CI, 2.1 to 3.6)
Kumar et al 20246

RCT		N=600 adults with Child-Pugh class B or C cirrhosis and UGIBTXA 1 gm IV loading dose, followed by 3 gm IV over 24 hours

Placebo
  • The proportion of patients with 5-day treatment failure was reduced with TXA (6.3%) versus placebo (13.3%; p=0.006).
  • EVL bleeding was reduced in patient who received TXA vs placebo (4.9 vs 12%, respectively; p=0.005).
  • 5- day and 6-week mortality rates were similar between groups (NS).
Abbreviations: CI=confidence interval; CVA=cerebrovascular accident; DB=double-blind; DVT=deep venous thrombosis; EVL=endoscopic variceal ligation; GI=gastrointestinal LGIB=lower gastrointestinal bleeding; LOS=length of stay; MA=meta-analysis; MD=mean difference; MI=myocardial infarction; NGT=nasogastric tube; NS=nonsignificant; OR=odds ratio; PE=pulmonary embolism; pRBC=packed red blood cells; PPI=proton pump inhibitor; PO=by mouth; PSM=propensity-score matching; RCT=randomized controlled trial; RR=risk ratio; SC=single center; SR=systematic review; TXA=tranexamic acid; UGIB=upper gastrointestinal bleeding.

Conclusion
The updated ACG guidelines on management of LGIB now recommend against the use of TXA due to the lack of benefit on mortality, Hgb levels, and transfusion rates and volumes with oral or IV TXA. In LGIB, 2 newer meta-analyses have confirmed the lack of mortality benefit with TXA, with 1 demonstrating a potential mortality increase. One small RCT also found no difference in blood requirements in patients with LGIB who received TXA versus placebo.

In UGIB, 2 meta-analyses demonstrated a potential mortality benefit with TXA. A smaller meta-analysis in UGIB also found that combined acid suppressive therapy with TXA reduced the risk of rebleeding. A large RCT of patients with liver disease and UGIB also found that TXA improved the failure to control bleeding by day 5. In a retrospective study of patients with gastric cancer and UGIB, successful hemostasis was increased and secondary bleeding rates were reduced in those who received TXA with acid suppression versus acid suppression alone. Additionally, a large retrospective study reported an increased rate of cardiovascular and thrombotic events in patients who received TXA for UGIB, although after incorporation of this study into the meta-analyses by Calderon Martinez and colleagues, the overall risk of thrombotic events with TXA was not significantly increased.

Overall, further study is needed to determine the role of TXA in UGIB and the optimal dosing regimen, as dosing greatly varied across studies. Further study is also needed to elucidate the risk of thromboembolism with TXA when used for GI bleeding. The use of TXA in combination with acid suppression, and in patients with gastric cancer or liver disease with UGIB also warrants further investigation.

References

  1. Buege M. What is the role of tranexamic acid in patients with acute gastrointestinal bleeding? Published December 2022. Accessed June 18, 2025. https://dig.pharmacy.uic.edu/faqs/2022-2/december-2022-faqs/what-is-the-role-of-tranexamic-acid-in-patients-with-acute-gastrointestinal-bleeding/
  2. Sengupta N, Feuerstein JD, Jairath V, et al. Management of patients with acute lower gastrointestinal bleeding: An updated ACG guideline. Am J Gastroenterol. 2023;118(2):208-231. doi:10.14309/ajg.0000000000002130
  3. Laine L, Barkun AN, Saltzman JR, et al. ACG Clinical Guideline: Upper gastrointestinal and ulcer bleeding. Am J Gastroenterol. 2021;116(5):899-917. doi:10.14309/ajg.0000000000001245
  4. Calderon Martinez E, Briceño Silva GD, Sanchez Cruz C, et al. Tranexamic acid as treatment for acute gastrointestinal bleeding: A comprehensive systematic review and meta-analysis. Indian J Gastroenterol. 2025;44(3):311-329. doi:10.1007/s12664-025-01749-9
  5. O’Donnell O, Gallagher C, Davey MG, et al. A systematic review and meta-analysis assessing the use of tranexamic acid (TXA) in acute gastrointestinal bleeding. Ir J Med Sci. 2024;193(2):705-719. doi:10.1007/s11845-023-03517-0
  6. Kumar M, Venishetty S, Jindal A, et al. Tranexamic acid in upper gastrointestinal bleed in patients with cirrhosis: A randomized controlled trial. Hepatology. 2024;80(2):376-388. doi:10.1097/HEP.0000000000000817
  7. Kan SW, Tan YP, Tay MZ, et al. Tranexamic acid with acid suppression versus acid suppression alone as therapy for upper gastrointestinal bleeding: A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2025;40(2):398-403. doi:10.1111/jgh.16842
  8. Fowler C, Nasser J, Fera B, et al. Tranexamic acid in upper gastrointestinal bleeding is associated with venous and arterial thromboembolic events. Crit Care Explor. 2024;6(3):e1060. Published 2024 Mar 12. doi:10.1097/CCE.0000000000001060
  9. Moscovici A, Nasasra A, Hammerschlag J, et al. The effect of tranexamic acid on blood transfusion in lower gastrointestinal bleeding-A double blind prospective randomised controlled trial. World J Surg. 2024;48(8):2016-2021. doi:10.1002/wjs.12282
  10. Bai Z, Wang L, Yu B. Efficacy and safety of tranexamic acid in the treatment of gastric cancer complicated with upper gastrointestinal bleeding. Am J Transl Res. 2024;16(3):925-932. Published 2024 Mar 15. doi:10.62347/KOLI5819

Prepared by:
Christie Denton, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago Retzky College of Pharmacy

July 2025

The information presented is current as of June 18, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.