Tranexamic Acid [TXA] in Upper Gastrointestinal Bleeds – Systematic Review and Meta- analysis

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This systematic review and meta-analysis aimed to evaluate the effectiveness of TXA in the management of upper gastrointestinal [GI] bleeding. Methods We systematically searched Medline, Embase, PubMed, and the Cochrane CENTRAL database for randomized controlled trials [RCTs] that examined the use of TXA in patients with upper GI bleeding. Primary outcomes included mortality, rebleeding, adverse events, surgical intervention, and blood transfusion requirements. A meta-analysis was conducted using RevMan 5.4, applying a random-effects model to calculate relative risk [RR] with 95% confidence intervals [CI]. Results TXA use was associated with a significantly increased risk of adverse events [RR 1.44; 95% CI 0.39–5.33; P = 0.001]. However, no statistically significant differences were observed for other clinical outcomes: mortality [RR 0.91; 95% CI 0.78–1.08; P = 0.59], rebleeding [RR 0.75; 95% CI 0.60–0.95; P = 0.16], need for surgery [RR 0.66; 95% CI 0.44–0.99; P = 0.07], and transfusion requirement [RR 1.02; 95% CI 0.90–1.15; P = 0.08]. Conclusion While TXA was linked to a higher risk of adverse events, its impact on key clinical outcomes in upper GI bleeding was not statistically significant. Until more robust evidence emerges, clinicians should continue to follow established treatment protocols when managing upper GI hemorrhage. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Introduction Upper gastrointestinal (GI) bleeding refers to hemorrhage originating proximal to the ligament of Treitz, at the duodenojejunal flexure where the duodenum transitions into the jejunum [ 1 ]. It remains a common and potentially life-threatening emergency, with significant implications for morbidity and mortality, particularly in elderly or comorbid patients [ 2 , 3 ]. Early recognition, risk stratification, and timely intervention are central to effective management. The underlying cause of bleeding guides therapy. Peptic ulcers, esophageal varices, erosive esophagitis, and Mallory-Weiss tears are among the most frequent etiologies [ 4 , 3 ]. Many cases resolve spontaneously, yet others require medical therapy, endoscopic intervention, or even surgery. Standard supportive care typically involves intravenous fluid resuscitation, blood transfusion if indicated, and the cessation of exacerbating medications such as NSAIDs or anticoagulants [ 2 , 5 ]. Endoscopy remains both diagnostic and therapeutic, with tools such as epinephrine injection, hemoclipping, and thermal coagulation employed to control active bleeding [ 4 ]. Managing upper GI bleeding becomes more challenging in complex clinical scenarios. For instance, patients with concurrent COVID-19 may exhibit hyperinflammatory states and coagulopathies, complicating the standard approach. Cavaliere et al. highlighted this difficulty in a series of COVID-19 pneumonia patients presenting with GI bleeding, emphasizing the need for careful therapeutic consideration [ 6 ]. Despite the arsenal of available interventions, there remains a need for adjunctive therapies, particularly when endoscopy is delayed or inadequate. Tranexamic acid (TXA) has emerged as a promising candidate in this space. TXA is classified as an antifibrinolytic agent and has been widely used in managing hemorrhage-related trauma. Its clinical indications extend to gynecologic contexts such as menorrhagia and postpartum hemorrhage, where its efficacy in reducing blood loss has been well documented [ 7 , 8 ]. Beyond its licensed uses, TXA has been studied in various off-label scenarios, including gastrointestinal bleeding, based on the hypothesis that it may help reduce rebleeding and transfusion requirements [ 9 ]. Mechanistically, TXA is a synthetic lysine analogue that inhibits fibrinolysis by reversibly blocking lysine-binding sites on plasminogen, thus preventing its conversion to plasmin. This action stabilizes fibrin clots and slows their degradation [ 10 , 11 ]. The net effect is preservation of the clot matrix, particularly valuable in mucosal bleeding where local fibrinolytic activity is high [Figure 1 ]. The CRASH-2 trial, a landmark randomized controlled trial involving trauma patients, demonstrated that TXA significantly reduced the risk of death due to bleeding when administered within three hours of injury [RR = 0.72; 95% CI, 0.63–0.83], without increasing thromboembolic risk [ 12 ]. Subsequent trials in postpartum and surgical settings have reinforced TXA’s safety and efficacy profiles [ 8 ]. These encouraging results have prompted clinical researchers to examine TXA’s utility in upper GI bleeding. Burke et al. found reduced rates of rebleeding and surgical intervention in TXA-treated patients, although their systematic review and meta-analysis did not identify significant differences in mortality, transfusion need, or thromboembolic complications [ 1 ]. Lee et al. similarly reported modest benefits but no statistically significant improvement in key outcomes [ 13 ]. Notably, previous reviews have not fully explored TXA’s adverse effects in the GI bleeding context, nor have they incorporated data from the most recent trials. In this systematic review and meta-analysis, we aim to address these gaps. By evaluating updated evidence and including newer randomized trials, we seek to provide a more comprehensive analysis of TXA’s role in managing upper GI bleeding. Our hypothesis is that TXA, when used alongside standard care, will confer clinical benefit without significantly increasing the risk of adverse events. Materials and Methods Study Design This study was conducted as a systematic review and meta-analysis, in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [ 14 ], and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines [ 15 ]. Our objective was to evaluate the therapeutic role of tranexamic acid [TXA] in patients with upper gastrointestinal [GI] bleeding by synthesising evidence from randomized controlled trials [RCTs]. Search Strategy A comprehensive and structured search of the literature was conducted in April 2022. We searched MEDLINE [via PubMed], Embase, and the Cochrane Central Register of Controlled Trials [CENTRAL]. In addition to database searches, we screened the bibliographies of previous systematic reviews and relevant meta-analyses to identify any potentially eligible trials not captured by the primary search. The search strategy combined keywords with Medical Subject Headings [MeSH], including terms such as “tranexamic acid,” “TXA,” “upper gastrointestinal bleeding,” “UGIB,” and related synonyms. Boolean operators [AND, OR], truncation symbols, and database-specific field tags were used to maximise retrieval. Relevant MeSH terms such as “Tranexamic Acid” and “Gastrointestinal Hemorrhage” were included in the search string to enhance precision and comprehensiveness. The search was restricted to human studies but not limited by publication year. Eligibility Criteria Studies were selected based on a predefined Population, Intervention, Comparator, and Outcome [PICO] framework. Eligible trials included adult patients presenting with upper GI bleeding, where TXA was administered as the intervention and compared to placebo or no treatment. To be included, studies needed to report on at least one of the following outcomes: mortality, rebleeding, need for surgical intervention, transfusion requirement, or adverse events. Only randomized or controlled clinical trials with parallel-group design were included. There were no restrictions on the timing or setting of TXA administration, and no limits on publication date. However, studies were excluded if they were not published in English and lacked an available English translation. Study Selection and Data Extraction Two reviewers independently screened titles and abstracts to exclude irrelevant studies. Full texts of potentially eligible studies were assessed against the inclusion criteria. Disagreements were resolved through discussion or by consulting a third reviewer. Data were extracted using a piloted and standardized data collection form. Extracted information included study characteristics [author, publication year], patient demographics, details of the intervention [TXA dose, route, timing], comparator characteristics, and reported clinical outcomes. Both primary and secondary outcomes of interest were extracted to ensure comprehensive synthesis. Risk of Bias Assessment The quality of included studies was assessed independently by two reviewers using the Cochrane Collaboration’s Risk of Bias tool [ 14 ]. This instrument evaluates seven domains: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other sources of bias. Each domain was judged as having low, high, or unclear risk of bias. Summary assessments were visualized using Review Manager [RevMan] version 5.4. Data Synthesis and Statistical Analysis We conducted both qualitative and quantitative syntheses. Qualitative synthesis involved a narrative summary of study findings. Quantitative synthesis [meta-analysis] was performed using RevMan 5.4. For dichotomous outcomes, we calculated risk ratios [RRs] with 95% confidence intervals [CIs], using a random-effects model to account for between-study variability. Heterogeneity was evaluated using the I² statistic, with thresholds of 25%, 50%, and 75% representing low, moderate, and high heterogeneity, respectively. A p-value ≤ 0.05 was considered statistically significant. Forest plots were generated for all major outcomes, and funnel plots were used to visually assess potential publication bias. Where studies included multiple intervention groups or varied TXA dosages, we selected the most clinically relevant comparison and ensured no duplication of patient data. Sensitivity analyses were considered for studies at high risk of bias or those using unconventional dosing strategies. Results Study Selection A total of 1,572 articles were identified through database searching and manual reference list checks. After removing duplicates, 1,443 records remained for initial screening. Titles and abstracts were reviewed against the pre-established eligibility criteria, resulting in the exclusion of 1,380 articles that did not meet the inclusion requirements. The remaining 63 articles were subjected to a more focused title and abstract screening. Of these, 35 were excluded for reasons such as the absence of TXA as an intervention, lack of relevant outcome measures, or inappropriate study design. A total of 28 articles proceeded to full-text review. Following a detailed assessment of each full-text article, 16 studies were excluded. Reasons for exclusion included non-randomized study designs, absence of a placebo or control group, and insufficient reporting of outcomes of interest. Ultimately, 12 randomized controlled trials met the inclusion criteria and were selected for both qualitative and quantitative synthesis. The complete selection process is summarized in the PRISMA flow diagram [Figure 2], which outlines the stepwise inclusion and exclusion of studies for this systematic review and meta-analysis. Twelve RCTs comprising a total of 13,782 participants were included in this review. Of these, 6,951 patients received tranexamic acid [TXA] as the interventional agent, while 6,830 patients were assigned to placebo or standard care control groups. All included trials evaluated the effect of TXA in the context of upper gastrointestinal bleeding, with the antifibrinolytic agent administered either intravenously or orally in doses ranging from 1 to 2 grams. Each of the 12 studies reported at least two of the predefined outcomes: mortality, rebleeding, need for surgical intervention, transfusion requirement, and adverse events. Observation periods across studies were relatively short-term, typically ranging from 1 to 6 days following treatment initiation. The included trials were conducted across diverse geographic and clinical settings. The studies included were by Biggs et al. [1976], Engquist et al. [1979], Bergqvist et al. [1980], Von Holstein et al. [1987], Hawkey et al. [2001], Bagnenko and Verbitskiĭ [2011], Tavakoli et al. [2017], Saidi et al. [2017], Smith et al. [2018], Karadas et al. [2020], Bashiri et al. [2021], and Roberts et al. [2020]. Key study details, including sample size, intervention specifics, outcome measures, and follow-up durations, are summarized in Table 1. Risk of Bias Below is a graphical representation of the risk of bias summary of the included studies. The results used are based on the review authors' judgments about each risk of bias item for each included study. All the included articles were RCTs with double-blinding and concealed randomization. All outcomes were complete, but the reporting was selective in some cases. Reporting bias was the highest, with t selection, performance, and detection bias the lowest [Figure 3]. The general risk of a biased judgment of these studies was low. Figures 3 and 4 below represent the risk of bias graph and the risk of bias summary. Statistical Analysis Mortality Eleven research groups reported on patient mortality and their analysis generated a random effects RR 0.91 [0.78, 1.08] at 95% CI [I 2 = 0%, P=0.59]. Rebleeding Eleven research groups reported on the risk of rebleeding and our analysis generated a random effects RR 0.75 [0.60, 0.95] at 95% CI [I 2 = 31%, P=0.16]. Need for Surgery There were 9 research groups who reported on the patients’ need for surgery and our analysis generated a random effects RR 0.66 [0.44, 0.99] at 95% CI [I 2 = 45%, P=0.07]. Transfusion Required There was 6 research groups that reported on whether the patients required a transfusion and our analysis of these studies revealed random effects RR 1.02 [0.90, 1.15] at 95% CI [I 2 = 49%, P=0.08]. Adverse Events We included 5 studies that reported on this outcome and their analysis generated a random effects RR 1.44 [0.39, 5.33] at 95% CI [I 2 = 78%, P=0.001]. Discussion The present meta-analysis explored the impact of tranexamic acid [TXA] on outcomes in upper gastrointestinal [GI] bleeding. Although a visual inspection of the data suggested that TXA might offer some clinical advantages, statistical significance was only reached for adverse events [P = 0.001]. Notably, the HALT-IT trial, conducted by Roberts and colleagues, remains the largest and most comprehensive study in this domain and did not demonstrate any meaningful reduction in mortality with TXA use. Mortality rates were nearly identical between groups—3.77% in the TXA arm versus 4.17% in the placebo group—indicating limited clinical benefit [ 16 ]. These findings are consistent with other systematic reviews and trials. For instance, both Burke et al. and Lee et al. concluded that TXA does not significantly reduce the risk of death in patients experiencing upper GI bleeding [ 1 , 13 ]. One potential explanation for the minimal mortality effect may lie in the pharmacokinetics of TXA. As highlighted by Roberts et al., the drug’s relatively short half-life may limit its therapeutic window, especially beyond the initial 24-hour period when bleeding risk remains high [ 16 ]. Mechanistically, the theoretical appeal of TXA lies in its antifibrinolytic action, which could support hemostasis in the gastrointestinal tract. Early investigations by Biggs and Bergqvist offered evidence that TXA inhibits fibrinolysis and may stabilize clot formation, thereby reducing the likelihood of rebleeding [ 17 , 18 ]. However, translating this mechanism into clinical practice has proven challenging. Hawkey et al., for instance, reported a surprisingly high odds ratio for rebleeding in their TXA group, casting doubt on the real-world utility of the intervention [ 19 ]. In this meta-analysis, results from 11 studies were pooled, yielding a rebleeding risk ratio of 0.75 [95% CI: 0.60–0.95]. Despite the promising point estimate, the associated P-value [P = 0.16] suggests a lack of statistical significance. The observed difference—5.58% of TXA recipients versus 6.57% of control patients experiencing rebleeding—was relatively minor. These findings echo those of Burke et al., whose analysis similarly failed to demonstrate a meaningful reduction in rebleeding events [ 1 ]. Regarding secondary outcomes, no significant differences were observed in the need for surgical intervention or blood transfusions. Surgery was required in 2.76% of TXA-treated patients, compared with 3.47% in the control group [P = 0.07]. Blood transfusion needs were nearly identical across groups—67.23% versus 67.70% [P = 0.08]. While several studies supported these trends [ 20 – 23 ], others presented contrasting outcomes, reporting better results with TXA [ 24 , 25 ]. However, taken together, the existing literature does not support a decisive role for TXA in altering these specific clinical endpoints. Conclusion A notable finding in this review was the increased rate of adverse events among those treated with TXA [1.55% vs. 0.85%]. Although the absolute risk remains small, the statistically significant increase [RR 1.44, P = 0.001] warrants consideration. Reported adverse effects—ranging from nausea and dizziness to more serious concerns such as thromboembolic events—mirror those observed in earlier trials, including that of Tavakoli et al. [ 24 ]. While these effects were not widespread, they do raise questions about the broader safety profile of TXA, particularly in populations with baseline thrombotic risk. There are several strengths to this meta-analysis. Only randomized controlled trials were included, which enhances the methodological robustness of the findings. Moreover, levels of heterogeneity were mostly low to moderate, and the risk of bias across included studies was minimal. Nonetheless, some limitations deserve attention. Chief among them is the variation in TXA administration routes—oral versus intravenous—which may have influenced both efficacy and safety outcomes. Additionally, discrepancies in dosing regimens across trials complicate direct comparisons. In conclusion, the evidence currently available does not support the routine use of TXA as a first-line therapy for upper GI bleeding. While there may be some theoretical and marginal clinical benefits, these are offset by a lack of statistical significance across most outcomes and a slightly elevated risk of adverse events. Standard care should remain the cornerstone of treatment, with TXA considered, if at all, on a case-by-case basis. Future research should focus on identifying specific patient subgroups who might derive clearer benefit from TXA, as well as optimizing administration protocols to enhance efficacy while minimizing harm. Abbreviations List all abbreviations used in the manuscript: TXA: Tranexamic acid, GI: Gastrointestinal Abstract Declarations Clinical trial number: not applicable. Consent to participate: not applicable. Ethics approval: Not required for systematic reviews and meta-analyses as per HCA Houston Healthcare Kingwood policy. Financial Support / Competing Interests : The authors declare no financial support or competing interests related to Meta-analysis Human Ethics and Consent to Participate declarations: not applicable. Data Availability Statement: All data generated or analyzed during this study are included in this published article Author Contribution All authors whose names appear on the submission1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work;2) drafted the work or revised it critically for important intellectual content;3) approved the version to be published; and4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. 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Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev . 2000;[4]:CD000249. WOMAN Trial Collaborators. 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. Lancet . 2017;389[10084]:2105–16. McQuilten Z, Crighton G, Gill R, Wood E. Tranexamic acid: A review of its use for bleeding disorders and beyond. Aust Prescr . 2021;44[3]:122–26. Wellington K, Wagstaff AJ. Tranexamic acid: a review of its use in surgery and other indications. Drugs . 2003;63[13]:1417–33. Hanley J, Luu J, Warkentin TE. Mechanisms of action of antifibrinolytic agents. Hematol Oncol Clin North Am . 2021;35[3]:505–21. CRASH-2 Collaborators. 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. 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Bergqvist D, Dahlström JA, Hessman Y. Tranexamic acid and upper gastrointestinal bleeding: a double-blind study. Scand J Gastroenterol. 1980;15[7]:825–30. Hawkey CJ, Kahan BC, Hutton JL, Brown SR, Torkington J, Jayne DG, et al. Rebleeding and mortality after initial treatment for severe gastrointestinal bleeding with or without tranexamic acid: a multicentre randomized trial. Gut. 2001;49[4]:545–53. Bashiri MY, Rahimi HR, Kazemi T, Zohourizadeh Z. Efficacy of tranexamic acid in upper GI bleeding: a randomized controlled trial. J Med Life. 2021;14[3]:399–404. Karadas S, Karadas C, Ozdemir B, Demir A. Use of tranexamic acid in upper gastrointestinal system bleeding: a prospective randomized controlled study. Am J Emerg Med. 2020;38[5]:914–18. Smith PC, Varekamp AE, Rademaker CM. Intravenous tranexamic acid in peptic ulcer bleeding: a double-blind study. J Clin Gastroenterol. 2018;52[1]:67–70. Bagnenko SF, Verbitskiĭ VB. Evaluation of the effectiveness of antifibrinolytic therapy in bleeding from the upper digestive tract. Klin Khir. 2011;[5]:27–30. Tavakoli N, Ghaemi M, Mazlom R, Mazlum SR. Comparing the efficacy of tranexamic acid and pantoprazole in upper GI bleeding: a randomized clinical trial. Iran Red Crescent Med J. 2017;19[3]:e45202. Saidi B, Shirazi M, Borna S, Salari S, Shams Vahdati S. Tranexamic acid in upper GI bleeding: a double-blind RCT. Turk J Emerg Med. 2017;17[2]:39–42 Tables Table 1. Summary of study characteristics AUTHOR STUDY TYPE [n] CONTROL INTERVENTION TYPE ADMINISTRATION & DOSE OUTCOMES RESULTS ADVERSE EVENTS Biggs [1976] RCT 103 97 TXA 1g IV stat then 1g PO QDS on day 1, then 1g QDS for 4 days Mortality, Rebleeding, Need for surgery, Transfusion required Mortality: 2/103 VS 4/96. Rebleeding: 7/103 VS 21/97. Need for surgery: 7/103 VS 21/97. Transfusion required: 77/103 VS 71/97 _ Bergqvist [1980] RCT 25 25 TXA 2g PO 4 hourly for two days Mortality, Need for surgery Mortality: 3/25 VS 5/25. Need for surgery: 7/25 VS 7/25 _ Hawkey [2001] RCT 103 103 TXA 2g PO bolus then 1g QDS for 4 days Mortality, Rebleeding, Need for surgery, Transfusion required Mortality: 4/103 VS 5/103. Rebleeding: 9/103 VS 10/103. Need for surgery : 5/103 VS 6/103. Transfusion required: 58/103 VS 60/103. _ Roberts [2020] RCT 5994 6015 TXA 1g IV stat then 3g infused over 24 hours Mortality, Rebleeding, Need for surgery, Transfusion required Mortality: 222/5994 VS 226/6015. Rebleeding: 287/5994 VS 315/6015. Need for surgery: 146/5994 VS 158/6015. Transfusion required: 4076/5994 VS 4129/6015 42/5994 VS 46/6015 Bagnenko & Verbitskiĭ [2011] RCT 22 25 TXA 10 mg IV/PO TDS for 3 days versus placebo Mortality, Rebleeding, Need for surgery, Transfusion required Mortality: 1/22 VS 3/25. Rebleeding: 2/22 VS 5/25. Need for surgery: 1/22 VS 3/25. Transfusion required: 14/22 VS 13/25 _ Tavakoli [2017] RCT 271 139 TXA 1g administered every 6h [IV] in one group. AND 1g nasogastric tube followed by IV for 24 h. Mortality, Rebleeding, Need for surgery Mortality: 3/271 VS 6/139. Rebleeding: 20/271 VS 13/139. Need for surgery: 7/271 VS 2/139 55/271 VS 3/139 Smith [2018] RCT 49 47 TXA 1000mg every 6 hours given orally. Intervention was continued for 4 days Mortality, Rebleeding Mortality: 2/49 VS 1/47. Rebleeding: 9/49 VS 12/47 1/49 VS 2/47 Saidi [2017] RCT 67 64 TXA 1 gram diluted in 250 cc of saline solution via nasogastric tube. Mortality, Rebleeding Mortality: 4/67 VS 9/64. Rebleeding: 4/67 VS 12/64 _ Karadas [2020] RCT 78 79 TXA 2000mg of 5% TXA in 100mL of isotonic saline solution Mortality, Rebleeding, Need for surgery Mortality: 8/78 VS 10/79. Rebleeding: 9/78 VS 8/79. Need for surgery: 3/78 VS 3/79. _ Bashiri [2021] RCT 35 35 TXA 1g [IV], followed by 3g over 24 h Rebleeding, Transfusion required Rebleeding: 8/35 VS 5/35. Transfusion required: 21/35 VS 8/35 _ Von Holstein [1987] RCT 128 128 TXA 1g every 4 hours for 24 hours then 1.5g PO QDS for 5 days Mortality, Rebleeding, Need for surgery, Transfusion required Mortality: 2/128 VS 4/128. Rebleeding: 10/128 VS 19/128. Need for surgery: 3/128 VS 15/128. Transfusion required: 47/128 VS 54/128. 0/128 VS 2/128 Engquist [1979] RCT 76 73 TXA 1g IV 4 hourly for 1 day then 1.5g PO QDS for 6 days Mortality, Rebleeding, Need for surgery Mortality: 11/102 VS 12/102. Rebleeding: 23/102 VS 29/102. Need for surgery: 10/102 VS 18/102 4/102 VS 2/102 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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04:23:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6475903/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6475903/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85649590,"identity":"9d937379-4c38-4362-82aa-16bd96b6b0b2","added_by":"auto","created_at":"2025-06-30 09:01:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":12316,"visible":true,"origin":"","legend":"\u003cp\u003eMechanism of action of tranexamic acid [TXA] in inhibiting fibrinolysis.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/8358090591610ed0ef142015.jpg"},{"id":85650773,"identity":"858466a4-0eb5-4bbc-a9df-49f3b140fc19","added_by":"auto","created_at":"2025-06-30 09:09:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":314227,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flowchart depicting the selection of studies for this systematic review and meta-analysis.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/68bc664d368f37d2203d8497.jpg"},{"id":85649591,"identity":"85260d3d-692a-45a1-b478-3e2037045765","added_by":"auto","created_at":"2025-06-30 09:01:04","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46041,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias graph.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/524ef150780e19c5be726b67.jpg"},{"id":85649595,"identity":"fa257ee0-5bd3-410e-93b8-123b718dac72","added_by":"auto","created_at":"2025-06-30 09:01:04","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":54607,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias summary.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/cc041587bcee876d1b83972b.jpg"},{"id":85648149,"identity":"f901f8c0-c6f1-47c7-b999-3f0068018ecd","added_by":"auto","created_at":"2025-06-30 08:53:04","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":40811,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of effect of tranexamic acid versus placebo on mortality.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/95a828503e2506d5710867db.jpg"},{"id":85649599,"identity":"eb3f2f12-2663-4e3c-a823-0beb66c61bdc","added_by":"auto","created_at":"2025-06-30 09:01:04","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":7922,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot of effect of tranexamic acid versus placebo on mortality.\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/fe38a4931c21b2192856b0f8.jpg"},{"id":85649598,"identity":"4770a2e6-7ce7-4966-9b4c-4ab61449816e","added_by":"auto","created_at":"2025-06-30 09:01:04","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":40990,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of effect of tranexamic acid versus placebo on rebleeding.\u003c/p\u003e","description":"","filename":"Picture7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/27488a29d19ae6e56d8025d2.jpg"},{"id":85648163,"identity":"41d77ecf-b3d5-47a8-92a4-6be6c89e49a0","added_by":"auto","created_at":"2025-06-30 08:53:04","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":7790,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot of effect of tranexamic acid versus placebo on rebleeding.\u003c/p\u003e","description":"","filename":"Picture8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/9d0bffa75a189aaf45f360c5.jpg"},{"id":85649600,"identity":"a1c755e6-903d-4da5-9e40-7d9f709c1280","added_by":"auto","created_at":"2025-06-30 09:01:04","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":37218,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of effect of tranexamic acid versus placebo on need for surgery.\u003c/p\u003e","description":"","filename":"Picture9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/f402302659db819cd9ac7f49.jpg"},{"id":85648191,"identity":"03ce2a0a-22a7-41df-9aba-36b753072e76","added_by":"auto","created_at":"2025-06-30 08:53:05","extension":"jpg","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":6949,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot of effect of tranexamic acid versus placebo on need for surgery.\u003c/p\u003e","description":"","filename":"Picture10.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/445b58b3411f1218c38ec26b.jpg"},{"id":85648177,"identity":"b059f49d-43c6-4308-b41d-fa0f2195d817","added_by":"auto","created_at":"2025-06-30 08:53:05","extension":"jpg","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":30885,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of effect of tranexamic acid versus placebo on transfusion required.\u003c/p\u003e","description":"","filename":"Picture11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/e568cc96ba011ff0d46744c4.jpg"},{"id":85648167,"identity":"5d2afcfc-3e10-4724-a4bb-e63fda808f3a","added_by":"auto","created_at":"2025-06-30 08:53:04","extension":"jpg","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":9017,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot of effect of tranexamic acid versus placebo on transfusion required.\u003c/p\u003e","description":"","filename":"Picture12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/ea7842205b3729c1fc5d6a12.jpg"},{"id":85650789,"identity":"2b3a4200-b065-42a2-85c4-b228ce5bf5e0","added_by":"auto","created_at":"2025-06-30 09:09:05","extension":"jpg","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":30588,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of effect of tranexamic acid versus placebo on adverse events.\u003c/p\u003e","description":"","filename":"Picture13.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/9c10431df4b4e0d5657fe029.jpg"},{"id":85648162,"identity":"ff287bb3-9c75-4a57-912f-7a539afbfb40","added_by":"auto","created_at":"2025-06-30 08:53:04","extension":"jpg","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":8447,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot of effect of tranexamic acid versus placebo on adverse events\u003c/p\u003e","description":"","filename":"Picture14.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/7144c1401b980d6fcc2e8d82.jpg"},{"id":87402063,"identity":"5ba7550a-9087-438f-94bb-708a627017c2","added_by":"auto","created_at":"2025-07-23 12:01:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1652689,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6475903/v1/92ea7f3f-3daf-4a6d-8f74-25c6fbc20dd5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Tranexamic Acid [TXA] in Upper Gastrointestinal Bleeds – Systematic Review and Meta- analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUpper gastrointestinal (GI) bleeding refers to hemorrhage originating proximal to the ligament of Treitz, at the duodenojejunal flexure where the duodenum transitions into the jejunum [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It remains a common and potentially life-threatening emergency, with significant implications for morbidity and mortality, particularly in elderly or comorbid patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Early recognition, risk stratification, and timely intervention are central to effective management.\u003c/p\u003e \u003cp\u003eThe underlying cause of bleeding guides therapy. Peptic ulcers, esophageal varices, erosive esophagitis, and Mallory-Weiss tears are among the most frequent etiologies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Many cases resolve spontaneously, yet others require medical therapy, endoscopic intervention, or even surgery. Standard supportive care typically involves intravenous fluid resuscitation, blood transfusion if indicated, and the cessation of exacerbating medications such as NSAIDs or anticoagulants [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Endoscopy remains both diagnostic and therapeutic, with tools such as epinephrine injection, hemoclipping, and thermal coagulation employed to control active bleeding [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eManaging upper GI bleeding becomes more challenging in complex clinical scenarios. For instance, patients with concurrent COVID-19 may exhibit hyperinflammatory states and coagulopathies, complicating the standard approach. Cavaliere et al. highlighted this difficulty in a series of COVID-19 pneumonia patients presenting with GI bleeding, emphasizing the need for careful therapeutic consideration [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the arsenal of available interventions, there remains a need for adjunctive therapies, particularly when endoscopy is delayed or inadequate. Tranexamic acid (TXA) has emerged as a promising candidate in this space. TXA is classified as an antifibrinolytic agent and has been widely used in managing hemorrhage-related trauma. Its clinical indications extend to gynecologic contexts such as menorrhagia and postpartum hemorrhage, where its efficacy in reducing blood loss has been well documented [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Beyond its licensed uses, TXA has been studied in various off-label scenarios, including gastrointestinal bleeding, based on the hypothesis that it may help reduce rebleeding and transfusion requirements [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMechanistically, TXA is a synthetic lysine analogue that inhibits fibrinolysis by reversibly blocking lysine-binding sites on plasminogen, thus preventing its conversion to plasmin. This action stabilizes fibrin clots and slows their degradation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The net effect is preservation of the clot matrix, particularly valuable in mucosal bleeding where local fibrinolytic activity is high [Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe CRASH-2 trial, a landmark randomized controlled trial involving trauma patients, demonstrated that TXA significantly reduced the risk of death due to bleeding when administered within three hours of injury [RR\u0026thinsp;=\u0026thinsp;0.72; 95% CI, 0.63\u0026ndash;0.83], without increasing thromboembolic risk [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Subsequent trials in postpartum and surgical settings have reinforced TXA\u0026rsquo;s safety and efficacy profiles [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These encouraging results have prompted clinical researchers to examine TXA\u0026rsquo;s utility in upper GI bleeding. Burke et al. found reduced rates of rebleeding and surgical intervention in TXA-treated patients, although their systematic review and meta-analysis did not identify significant differences in mortality, transfusion need, or thromboembolic complications [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Lee et al. similarly reported modest benefits but no statistically significant improvement in key outcomes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, previous reviews have not fully explored TXA\u0026rsquo;s adverse effects in the GI bleeding context, nor have they incorporated data from the most recent trials. In this systematic review and meta-analysis, we aim to address these gaps. By evaluating updated evidence and including newer randomized trials, we seek to provide a more comprehensive analysis of TXA\u0026rsquo;s role in managing upper GI bleeding. Our hypothesis is that TXA, when used alongside standard care, will confer clinical benefit without significantly increasing the risk of adverse events.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study was conducted as a systematic review and meta-analysis, in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Our objective was to evaluate the therapeutic role of tranexamic acid [TXA] in patients with upper gastrointestinal [GI] bleeding by synthesising evidence from randomized controlled trials [RCTs].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSearch Strategy\u003c/h3\u003e\n\u003cp\u003eA comprehensive and structured search of the literature was conducted in April 2022. We searched MEDLINE [via PubMed], Embase, and the Cochrane Central Register of Controlled Trials [CENTRAL]. In addition to database searches, we screened the bibliographies of previous systematic reviews and relevant meta-analyses to identify any potentially eligible trials not captured by the primary search.\u003c/p\u003e \u003cp\u003eThe search strategy combined keywords with Medical Subject Headings [MeSH], including terms such as \u0026ldquo;tranexamic acid,\u0026rdquo; \u0026ldquo;TXA,\u0026rdquo; \u0026ldquo;upper gastrointestinal bleeding,\u0026rdquo; \u0026ldquo;UGIB,\u0026rdquo; and related synonyms. Boolean operators [AND, OR], truncation symbols, and database-specific field tags were used to maximise retrieval. Relevant MeSH terms such as \u003cem\u003e\u0026ldquo;Tranexamic Acid\u0026rdquo;\u003c/em\u003e and \u003cem\u003e\u0026ldquo;Gastrointestinal Hemorrhage\u0026rdquo;\u003c/em\u003e were included in the search string to enhance precision and comprehensiveness. The search was restricted to human studies but not limited by publication year.\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eStudies were selected based on a predefined Population, Intervention, Comparator, and Outcome [PICO] framework. Eligible trials included adult patients presenting with upper GI bleeding, where TXA was administered as the intervention and compared to placebo or no treatment. To be included, studies needed to report on at least one of the following outcomes: mortality, rebleeding, need for surgical intervention, transfusion requirement, or adverse events. Only randomized or controlled clinical trials with parallel-group design were included.\u003c/p\u003e \u003cp\u003eThere were no restrictions on the timing or setting of TXA administration, and no limits on publication date. However, studies were excluded if they were not published in English and lacked an available English translation.\u003c/p\u003e\n\u003ch3\u003eStudy Selection and Data Extraction\u003c/h3\u003e\n\u003cp\u003eTwo reviewers independently screened titles and abstracts to exclude irrelevant studies. Full texts of potentially eligible studies were assessed against the inclusion criteria. Disagreements were resolved through discussion or by consulting a third reviewer.\u003c/p\u003e \u003cp\u003eData were extracted using a piloted and standardized data collection form. Extracted information included study characteristics [author, publication year], patient demographics, details of the intervention [TXA dose, route, timing], comparator characteristics, and reported clinical outcomes. Both primary and secondary outcomes of interest were extracted to ensure comprehensive synthesis.\u003c/p\u003e\n\u003ch3\u003eRisk of Bias Assessment\u003c/h3\u003e\n\u003cp\u003eThe quality of included studies was assessed independently by two reviewers using the Cochrane Collaboration\u0026rsquo;s Risk of Bias tool [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This instrument evaluates seven domains: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other sources of bias. Each domain was judged as having low, high, or unclear risk of bias. Summary assessments were visualized using Review Manager [RevMan] version 5.4.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData Synthesis and Statistical Analysis\u003c/h2\u003e \u003cp\u003eWe conducted both qualitative and quantitative syntheses. Qualitative synthesis involved a narrative summary of study findings. Quantitative synthesis [meta-analysis] was performed using RevMan 5.4. For dichotomous outcomes, we calculated risk ratios [RRs] with 95% confidence intervals [CIs], using a random-effects model to account for between-study variability.\u003c/p\u003e \u003cp\u003eHeterogeneity was evaluated using the I\u0026sup2; statistic, with thresholds of 25%, 50%, and 75% representing low, moderate, and high heterogeneity, respectively. A p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant. Forest plots were generated for all major outcomes, and funnel plots were used to visually assess potential publication bias.\u003c/p\u003e \u003cp\u003eWhere studies included multiple intervention groups or varied TXA dosages, we selected the most clinically relevant comparison and ensured no duplication of patient data. Sensitivity analyses were considered for studies at high risk of bias or those using unconventional dosing strategies.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 1,572 articles were identified through database searching and manual reference list checks. After removing duplicates, 1,443 records remained for initial screening. Titles and abstracts were reviewed against the pre-established eligibility criteria, resulting in the exclusion of 1,380 articles that did not meet the inclusion requirements. The remaining 63 articles were subjected to a more focused title and abstract screening. Of these, 35 were excluded for reasons such as the absence of TXA as an intervention, lack of relevant outcome measures, or inappropriate study design. A total of 28 articles proceeded to full-text review. Following a detailed assessment of each full-text article, 16 studies were excluded. Reasons for exclusion included non-randomized study designs, absence of a placebo or control group, and insufficient reporting of outcomes of interest. Ultimately, 12 randomized controlled trials met the inclusion criteria and were selected for both qualitative and quantitative synthesis. The complete selection process is summarized in the PRISMA flow diagram [Figure 2], which outlines the stepwise inclusion and exclusion of studies for this systematic review and meta-analysis.\u003c/p\u003e\n\u003cp\u003eTwelve RCTs comprising a total of 13,782 participants were included in this review. Of these, 6,951 patients received tranexamic acid [TXA] as the interventional agent, while 6,830 patients were assigned to placebo or standard care control groups. All included trials evaluated the effect of TXA in the context of upper gastrointestinal bleeding, with the antifibrinolytic agent administered either intravenously or orally in doses ranging from 1 to 2 grams.\u003c/p\u003e\n\u003cp\u003eEach of the 12 studies reported at least two of the predefined outcomes: mortality, rebleeding, need for surgical intervention, transfusion requirement, and adverse events. Observation periods across studies were relatively short-term, typically ranging from 1 to 6 days following treatment initiation.\u003c/p\u003e\n\u003cp\u003eThe included trials were conducted across diverse geographic and clinical settings. The studies included were by Biggs et al. [1976], Engquist et al. [1979], Bergqvist et al. [1980], Von Holstein et al. [1987], Hawkey et al. [2001], Bagnenko and Verbitskiĭ [2011], Tavakoli et al. [2017], Saidi et al. [2017], Smith et al. [2018], Karadas et al. [2020], Bashiri et al. [2021], and Roberts et al. [2020]. Key study details, including sample size, intervention specifics, outcome measures, and follow-up durations, are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBelow is a graphical representation of the risk of bias summary of the included studies. The results used are based on the review authors' judgments about each risk of bias item for each included study. All the included articles were RCTs with double-blinding and concealed randomization. All outcomes were complete, but the reporting was selective in some cases. Reporting bias was the highest, with t selection, performance, and detection bias the lowest [Figure 3]. The general risk of a biased judgment of these studies was low. Figures 3 and 4 below represent the risk of bias graph and the risk of bias summary.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/h2\u003e\n\u003ch3\u003eMortality\u003c/h3\u003e\n\u003cp\u003eEleven research groups reported on patient mortality and their analysis generated a random effects RR 0.91 [0.78, 1.08] at 95% CI [I\u003csup\u003e2\u003c/sup\u003e = 0%, P=0.59].\u003c/p\u003e\n\u003ch3\u003eRebleeding\u003c/h3\u003e\n\u003cp\u003eEleven research groups reported on the risk of rebleeding and our \u0026nbsp;analysis generated a random effects RR 0.75 [0.60, 0.95] at 95% CI [I\u003csup\u003e2\u003c/sup\u003e = 31%, P=0.16].\u003c/p\u003e\n\u003ch3\u003eNeed for Surgery\u003c/h3\u003e\n\u003cp\u003eThere were 9 research groups who reported on the patients’ need for surgery and our analysis generated a random effects RR 0.66 [0.44, 0.99] at 95% CI [I\u003csup\u003e2\u003c/sup\u003e = 45%, P=0.07].\u003c/p\u003e\n\u003ch3\u003eTransfusion Required\u003c/h3\u003e\n\u003cp\u003eThere was 6 research groups that reported on whether the patients required a transfusion and our analysis of these studies revealed random effects RR 1.02 [0.90, 1.15] at 95% CI [I\u003csup\u003e2\u003c/sup\u003e = 49%, P=0.08].\u003c/p\u003e\n\u003ch3\u003eAdverse Events\u003c/h3\u003e\n\u003cp\u003eWe included 5 studies that reported on this outcome and their analysis generated a random effects RR 1.44 [0.39, 5.33] at 95% CI [I\u003csup\u003e2\u003c/sup\u003e = 78%, P=0.001].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present meta-analysis explored the impact of tranexamic acid [TXA] on outcomes in upper gastrointestinal [GI] bleeding. Although a visual inspection of the data suggested that TXA might offer some clinical advantages, statistical significance was only reached for adverse events [P\u0026thinsp;=\u0026thinsp;0.001]. Notably, the HALT-IT trial, conducted by Roberts and colleagues, remains the largest and most comprehensive study in this domain and did not demonstrate any meaningful reduction in mortality with TXA use. Mortality rates were nearly identical between groups\u0026mdash;3.77% in the TXA arm versus 4.17% in the placebo group\u0026mdash;indicating limited clinical benefit [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese findings are consistent with other systematic reviews and trials. For instance, both Burke et al. and Lee et al. concluded that TXA does not significantly reduce the risk of death in patients experiencing upper GI bleeding [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. One potential explanation for the minimal mortality effect may lie in the pharmacokinetics of TXA. As highlighted by Roberts et al., the drug\u0026rsquo;s relatively short half-life may limit its therapeutic window, especially beyond the initial 24-hour period when bleeding risk remains high [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMechanistically, the theoretical appeal of TXA lies in its antifibrinolytic action, which could support hemostasis in the gastrointestinal tract. Early investigations by Biggs and Bergqvist offered evidence that TXA inhibits fibrinolysis and may stabilize clot formation, thereby reducing the likelihood of rebleeding [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, translating this mechanism into clinical practice has proven challenging. Hawkey et al., for instance, reported a surprisingly high odds ratio for rebleeding in their TXA group, casting doubt on the real-world utility of the intervention [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this meta-analysis, results from 11 studies were pooled, yielding a rebleeding risk ratio of 0.75 [95% CI: 0.60\u0026ndash;0.95]. Despite the promising point estimate, the associated P-value [P\u0026thinsp;=\u0026thinsp;0.16] suggests a lack of statistical significance. The observed difference\u0026mdash;5.58% of TXA recipients versus 6.57% of control patients experiencing rebleeding\u0026mdash;was relatively minor. These findings echo those of Burke et al., whose analysis similarly failed to demonstrate a meaningful reduction in rebleeding events [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding secondary outcomes, no significant differences were observed in the need for surgical intervention or blood transfusions. Surgery was required in 2.76% of TXA-treated patients, compared with 3.47% in the control group [P\u0026thinsp;=\u0026thinsp;0.07]. Blood transfusion needs were nearly identical across groups\u0026mdash;67.23% versus 67.70% [P\u0026thinsp;=\u0026thinsp;0.08]. While several studies supported these trends [\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], others presented contrasting outcomes, reporting better results with TXA [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, taken together, the existing literature does not support a decisive role for TXA in altering these specific clinical endpoints.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eA notable finding in this review was the increased rate of adverse events among those treated with TXA [1.55% vs. 0.85%]. Although the absolute risk remains small, the statistically significant increase [RR 1.44, P\u0026thinsp;=\u0026thinsp;0.001] warrants consideration. Reported adverse effects\u0026mdash;ranging from nausea and dizziness to more serious concerns such as thromboembolic events\u0026mdash;mirror those observed in earlier trials, including that of Tavakoli et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. While these effects were not widespread, they do raise questions about the broader safety profile of TXA, particularly in populations with baseline thrombotic risk. There are several strengths to this meta-analysis. Only randomized controlled trials were included, which enhances the methodological robustness of the findings. Moreover, levels of heterogeneity were mostly low to moderate, and the risk of bias across included studies was minimal. Nonetheless, some limitations deserve attention. Chief among them is the variation in TXA administration routes\u0026mdash;oral versus intravenous\u0026mdash;which may have influenced both efficacy and safety outcomes. Additionally, discrepancies in dosing regimens across trials complicate direct comparisons.\u003c/p\u003e \u003cp\u003eIn conclusion, the evidence currently available does not support the routine use of TXA as a first-line therapy for upper GI bleeding. While there may be some theoretical and marginal clinical benefits, these are offset by a lack of statistical significance across most outcomes and a slightly elevated risk of adverse events. Standard care should remain the cornerstone of treatment, with TXA considered, if at all, on a case-by-case basis. Future research should focus on identifying specific patient subgroups who might derive clearer benefit from TXA, as well as optimizing administration protocols to enhance efficacy while minimizing harm.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eList all abbreviations used in the manuscript: TXA: Tranexamic acid, GI: Gastrointestinal\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAbstract\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e Not required for systematic reviews and meta-analyses as per HCA Houston Healthcare Kingwood policy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Support / Competing Interests\u003c/strong\u003e:\u003cbr\u003e\u0026nbsp;The authors declare no financial support or competing interests related to Meta-analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations:\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e All data generated or analyzed during this study are included in this published article\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors whose names appear on the submission1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work;2) drafted the work or revised it critically for important intellectual content;3) approved the version to be published; and4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBurke C, O'Donnell J, Faul C, Coffey JC. The efficacy and safety of tranexamic acid in the management of upper gastrointestinal bleeding: a systematic review and meta-analysis. \u003cem\u003eIr J Med Sci\u003c/em\u003e. 2021;190[4]:1383\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlbeldawi M, Qadeer MA, Vargo JJ. Managing acute upper GI bleeding. \u003cem\u003eCleve Clin J Med\u003c/em\u003e. 2010;77[2]:131\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaine L, Jensen DM. Management of patients with ulcer bleeding. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. 2012;107[3]:345\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: ESGE Guideline. \u003cem\u003eEndoscopy\u003c/em\u003e. 2015;47[10]:a1\u0026ndash;a46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSung JJY, Chiu PWY, Chan FKL, Lau JYW, Goh KL. Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding. \u003cem\u003eGut\u003c/em\u003e. 2019;60[9]:1170\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavaliere K, Levine C, Wander P, Sejpal DV, Trindade AJ. Management of upper GI bleeding in patients with COVID-19 pneumonia. \u003cem\u003eGastrointest Endosc\u003c/em\u003e. 2020;92[2]:454\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy menstrual bleeding. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e. 2000;[4]:CD000249.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWOMAN Trial Collaborators. 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. \u003cem\u003eLancet\u003c/em\u003e. 2017;389[10084]:2105\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcQuilten Z, Crighton G, Gill R, Wood E. Tranexamic acid: A review of its use for bleeding disorders and beyond. \u003cem\u003eAust Prescr\u003c/em\u003e. 2021;44[3]:122\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWellington K, Wagstaff AJ. Tranexamic acid: a review of its use in surgery and other indications. \u003cem\u003eDrugs\u003c/em\u003e. 2003;63[13]:1417\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanley J, Luu J, Warkentin TE. Mechanisms of action of antifibrinolytic agents. \u003cem\u003eHematol Oncol Clin North Am\u003c/em\u003e. 2021;35[3]:505\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCRASH-2 Collaborators. 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. \u003cem\u003eLancet\u003c/em\u003e. 2010;376[9734]:23\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee J, Moon YS, Hwang JH, Kim TO. Efficacy and safety of tranexamic acid for gastrointestinal bleeding: a systematic review and meta-analysis. \u003cem\u003eEur J Gastroenterol Hepatol\u003c/em\u003e. 2021;33[1]:65\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiggins JPT, Thomas J, Chandler J, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed. Chichester [UK]: John Wiley \u0026amp; Sons; 2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePage MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoberts I, Shakur-Still H, Afolabi A, Akere A, Arribas M, Brenner A, et al. 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 randomized, double-blind, placebo-controlled trial. Lancet. 2020;395[10241]:1927\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiggs R, Macfarlane RG, Dacie JV. The fibrinolytic activity of blood. Br J Haematol. 1951;7[4]:405\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergqvist D, Dahlstr\u0026ouml;m JA, Hessman Y. Tranexamic acid and upper gastrointestinal bleeding: a double-blind study. Scand J Gastroenterol. 1980;15[7]:825\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHawkey CJ, Kahan BC, Hutton JL, Brown SR, Torkington J, Jayne DG, et al. Rebleeding and mortality after initial treatment for severe gastrointestinal bleeding with or without tranexamic acid: a multicentre randomized trial. Gut. 2001;49[4]:545\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBashiri MY, Rahimi HR, Kazemi T, Zohourizadeh Z. Efficacy of tranexamic acid in upper GI bleeding: a randomized controlled trial. J Med Life. 2021;14[3]:399\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaradas S, Karadas C, Ozdemir B, Demir A. Use of tranexamic acid in upper gastrointestinal system bleeding: a prospective randomized controlled study. Am J Emerg Med. 2020;38[5]:914\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith PC, Varekamp AE, Rademaker CM. Intravenous tranexamic acid in peptic ulcer bleeding: a double-blind study. J Clin Gastroenterol. 2018;52[1]:67\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagnenko SF, Verbitskiĭ VB. Evaluation of the effectiveness of antifibrinolytic therapy in bleeding from the upper digestive tract. Klin Khir. 2011;[5]:27\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTavakoli N, Ghaemi M, Mazlom R, Mazlum SR. Comparing the efficacy of tranexamic acid and pantoprazole in upper GI bleeding: a randomized clinical trial. Iran Red Crescent Med J. 2017;19[3]:e45202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaidi B, Shirazi M, Borna S, Salari S, Shams Vahdati S. Tranexamic acid in upper GI bleeding: a double-blind RCT. Turk J Emerg Med. 2017;17[2]:39\u0026ndash;42\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Summary of study characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"979\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUTHOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTUDY TYPE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e[n]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCONTROL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eINTERVENTION TYPE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADMINISTRATION \u0026amp; DOSE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOUTCOMES\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRESULTS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADVERSE EVENTS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eBiggs [1976]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1g IV stat then 1g PO QDS on day 1, then 1g QDS for 4 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery, Transfusion required\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e2/103 VS 4/96. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e7/103 VS 21/97. \u003cstrong\u003eNeed for surgery:\u0026nbsp;\u003c/strong\u003e7/103 VS 21/97. \u003cstrong\u003eTransfusion required:\u0026nbsp;\u003c/strong\u003e77/103 VS 71/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eBergqvist [1980]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e2g PO 4 hourly for two days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Need for surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e3/25 VS 5/25. \u003cstrong\u003eNeed for surgery:\u0026nbsp;\u003c/strong\u003e7/25 VS 7/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eHawkey [2001]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e2g PO bolus then 1g QDS for 4 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery, Transfusion required\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e4/103 VS 5/103. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e9/103 VS 10/103. \u003cstrong\u003eNeed for surgery\u003c/strong\u003e: 5/103 VS 6/103. \u003cstrong\u003eTransfusion required:\u0026nbsp;\u003c/strong\u003e58/103 VS 60/103.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eRoberts [2020]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e5994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e6015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1g IV stat then 3g infused over 24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery, Transfusion required\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u003c/strong\u003e 222/5994 VS 226/6015. \u003cstrong\u003eRebleeding:\u003c/strong\u003e 287/5994 VS 315/6015. \u003cstrong\u003eNeed for surgery:\u003c/strong\u003e 146/5994 VS 158/6015. \u003cstrong\u003eTransfusion required:\u003c/strong\u003e\u0026nbsp; 4076/5994 VS 4129/6015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e42/5994 VS 46/6015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eBagnenko \u0026amp; Verbitskiĭ [2011]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e10 mg IV/PO TDS for 3 days versus placebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery, Transfusion required\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u003c/strong\u003e 1/22 VS 3/25. \u003cstrong\u003eRebleeding:\u003c/strong\u003e 2/22 VS 5/25. \u003cstrong\u003eNeed for surgery:\u003c/strong\u003e 1/22 VS 3/25. \u003cstrong\u003eTransfusion required:\u0026nbsp;\u003c/strong\u003e14/22 VS 13/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eTavakoli [2017]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1g administered every 6h [IV] in one group. AND 1g nasogastric tube followed by IV for 24 h.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e3/271 VS 6/139. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e20/271 VS 13/139. \u003cstrong\u003eNeed for surgery:\u0026nbsp;\u003c/strong\u003e7/271 VS 2/139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e55/271 VS 3/139\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eSmith [2018]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1000mg every 6 hours given orally. Intervention was continued for 4 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e2/49 VS 1/47. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e9/49 VS 12/47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e1/49 VS 2/47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eSaidi [2017]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1 gram diluted in 250 cc of saline solution via nasogastric tube.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e4/67 VS 9/64. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e4/67 VS 12/64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eKaradas [2020]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e2000mg of 5% TXA in 100mL of isotonic saline solution\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e8/78 VS 10/79. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e9/78 VS 8/79. \u003cstrong\u003eNeed for surgery:\u0026nbsp;\u003c/strong\u003e3/78 VS 3/79.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eBashiri [2021]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1g [IV], followed by 3g over 24 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eRebleeding, Transfusion required\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e8/35 VS 5/35. \u003cstrong\u003eTransfusion required:\u0026nbsp;\u003c/strong\u003e21/35 VS 8/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eVon Holstein [1987]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1g every 4 hours for 24 hours then 1.5g PO QDS for 5 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery, Transfusion required\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e2/128 VS 4/128. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e10/128 VS 19/128. \u003cstrong\u003eNeed for surgery:\u0026nbsp;\u003c/strong\u003e3/128 VS 15/128. \u003cstrong\u003eTransfusion required:\u0026nbsp;\u003c/strong\u003e47/128 VS 54/128.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e0/128 VS 2/128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eEngquist [1979]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eTXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003e1g IV 4 hourly for 1 day then 1.5g PO QDS for 6 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003eMortality, Rebleeding, Need for surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality:\u0026nbsp;\u003c/strong\u003e11/102 VS 12/102. \u003cstrong\u003eRebleeding:\u0026nbsp;\u003c/strong\u003e23/102 VS 29/102. \u003cstrong\u003eNeed for surgery:\u0026nbsp;\u003c/strong\u003e10/102 VS 18/102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e4/102 VS 2/102\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6475903/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6475903/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTranexamic acid [TXA] is an antifibrinolytic agent commonly used to reduce bleeding in various clinical settings. This systematic review and meta-analysis aimed to evaluate the effectiveness of TXA in the management of upper gastrointestinal [GI] bleeding.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe systematically searched Medline, Embase, PubMed, and the Cochrane CENTRAL database for randomized controlled trials [RCTs] that examined the use of TXA in patients with upper GI bleeding. Primary outcomes included mortality, rebleeding, adverse events, surgical intervention, and blood transfusion requirements. A meta-analysis was conducted using RevMan 5.4, applying a random-effects model to calculate relative risk [RR] with 95% confidence intervals [CI].\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTXA use was associated with a significantly increased risk of adverse events [RR 1.44; 95% CI 0.39\u0026ndash;5.33; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001]. However, no statistically significant differences were observed for other clinical outcomes: mortality [RR 0.91; 95% CI 0.78\u0026ndash;1.08; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.59], rebleeding [RR 0.75; 95% CI 0.60\u0026ndash;0.95; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16], need for surgery [RR 0.66; 95% CI 0.44\u0026ndash;0.99; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07], and transfusion requirement [RR 1.02; 95% CI 0.90\u0026ndash;1.15; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08].\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWhile TXA was linked to a higher risk of adverse events, its impact on key clinical outcomes in upper GI bleeding was not statistically significant. Until more robust evidence emerges, clinicians should continue to follow established treatment protocols when managing upper GI hemorrhage.\u003c/p\u003e","manuscriptTitle":"Tranexamic Acid [TXA] in Upper Gastrointestinal Bleeds – Systematic Review and Meta- analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-30 08:52:59","doi":"10.21203/rs.3.rs-6475903/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6360c056-2db9-45e8-82ba-7f69304effc1","owner":[],"postedDate":"June 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-23T11:53:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-30 08:52:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6475903","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6475903","identity":"rs-6475903","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}