Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis
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ABSTRACT: Background
Tranexamic acid (TXA) reduces surgical bleeding and reduces death from bleeding after trauma and childbirth. However, its effects on thrombotic events and seizures are less clear. We conducted a systematic review and meta-analysis to examine the safety of TXA in bleeding patients. Methods
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials from inception until June 1, 2020. We included randomized trials comparing intravenous tranexamic acid and placebo or no intervention in bleeding patients. The primary outcomes were thrombotic events, venous thromboembolism, acute coronary syndrome, stroke and seizures. A meta-analysis was performed using a random effects model and meta-regression analysis was performed to evaluate how effects vary by dose. We assessed the certainty of evidence using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Results
A total of 234 studies with 102,681 patients were included in the meta-analysis. In bleeding patients, there was no evidence that TXA increased the risk of thrombotic events (RR = 1.00 [95% CI 0.93–1.08]), seizures (1.18 [0.91–1.53]), venous thromboembolism (1.04 [0.92–1.17]), acute coronary syndrome (0.88 [0.78–1.00]) or stroke (1.12 [0.98–1.27]). In a dose-by-dose sensitivity analysis, seizures were increased in patients receiving more than 2 g/day of TXA (3.05 [1.01–9.20]). Meta-regression showed an increased risk of seizures with increased dose of TXA (p = 0.011). Conclusion
Tranexamic acid did not appear to increase the risk of thrombotic events in bleeding patients. However, because there may be dose-dependent increase in the risk of seizures, very high doses should be avoided. Supplementary Information
The online version contains supplementary material available at 10.1186/s13054-021-03799-9.
SUBMITTER: Murao S
PROVIDER: S-EPMC8561958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients.DesignSystematic review and meta-analysis.Data sourcesCochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles.Study selectionRandomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status.Results129 trials, totalling 10,488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; P<0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; P<0.001). The effect of tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P = 0.11), stroke (1.14, 0.65 to 2.00; P = 0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P = 0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; P = 0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years.ConclusionsStrong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.
| S-EPMC3356857 | biostudies-literature
Project description:IntroductionTranexamic acid (TXA) is a synthetic derivative of the amino acid lysine that inhibits fibrinolysis by blocking lysine-binding sites on plasminogen, which contribute to reduced bleeding, the need for transfusion and mortality. Although there is reliable evidence of the efficacy of TXA, its effects on other important outcomes, adverse events, including thrombotic events and seizure, remain uncertain.Methods and analysisWe will conduct a systematic review and meta-analysis of randomised controlled trials with the objective of evaluating the incidence of thrombotic adverse events and seizure and how the effect of TXA varies by dose and underlying disease. We will include patients with bleeding in any underlying disease. We will search MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials for randomised controlled trials. The planned date of our systematic search is 1 June 2020. We will follow the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Subgroup and sensitivity analyses will be performed to explore residual heterogeneity and inconsistency. Meta-regression analysis will be carried out to investigate the association between the incidence of adverse events and the TXA dose. The risk of systematic errors (bias) and random errors will be assessed and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationThis study will not involve primary data collection, and formal ethics approval will therefore not be required. We aim to publish this systematic review in a peer-review journal.Trial registration numberUMIN000039611.
| S-EPMC7311044 | biostudies-literature
Project description:IntroductionGastrointestinal bleeding results in significant morbidity, cost and mortality. TXA, an antifibrinolytic agent, has been proposed to reduce mortality; however, many studies report conflicting results.MethodsThe aim of the study was to perform the first systematic review and meta-analysis of RCTs to evaluate the efficacy TXA for both upper and lower gastrointestinal bleeding. This was performed per PRISMA guidelines. PubMed, EMBASE, Cochrane and Scopus databases were searched for RCTs. Dichotomous variables were pooled as risk ratios (RR) with 95% confidence intervals (CI) using the MH method with random effects modelling.ResultsFourteen RCTs were identified with 14,338 patients and mean age of 58.4 years. 34.9% (n = 5008) were female and 65.1% (n = 9330) male. There was no significant difference in mortality between TXA and placebo (RR 0.86 95% CI (0.74 to 1.00), P: 0.05). The secondary outcomes, similarly, did not yield significant results. These included rebleeding, need for surgical intervention (RR: 0.75 95% CI (0.53, 1.07)), endoscopic intervention (RR: 0.92 95% CI (0.70, 1.22)), transfusion requirement (RR: 1.01 95% CI (0.94, 10.7)) and length of stay (RR: 0.03 95% CI (- 0.03, 0.08)). There was no increased risk of VTE, RR: 1.29 95% CI (0.53, 3.16). One trial (n = 12,009) reported an increased risk of seizure in the TXA group, RR: 1.73 95% CI (1.03-2.93).ConclusionTXA does not reduce mortality in patients with acute upper or lower gastrointestinal bleeding and may confer an increased risk of seizures. The authors do not recommend the use of TXA in acute gastrointestinal bleeding.
| S-EPMC10961292 | biostudies-literature
Project description:ImportanceTranexamic acid (TXA) is an efficient antifibrinolytic agent; however, concerns remain about the potential adverse effects, particularly vascular occlusive events, that may be associated with its use.ObjectiveTo examine the association between intravenous TXA and total thromboembolic events (TEs) and mortality in patients of all ages and of any medical disciplines.Data sourceCochrane Central Register of Controlled Trials and MEDLINE were searched for eligible studies investigating intravenous TXA and postinterventional outcome published between 1976 and 2020.Study selectionRandomized clinical trials comparing intravenous TXA with placebo/no treatment. The electronic database search yielded a total of 782 studies, and 381 were considered for full-text review. Included studies were published in English, German, French, and Spanish. Studies with only oral or topical tranexamic administration were excluded.Data extraction and synthesisMeta-analysis, subgroup and sensitivity analysis, and meta-regression were performed. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Main outcomes and measuresVascular occlusive events and mortality.ResultsA total of 216 eligible trials including 125 550 patients were analyzed. Total TEs were found in 1020 (2.1%) in the group receiving TXA and 900 (2.0%) in the control group. This study found no association between TXA and risk for total TEs (risk difference = 0.001; 95% CI, -0.001 to 0.002; P = .49) for venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, and cerebral infarction or ischemia. Sensitivity analysis using the risk ratio as an effect measure with (risk ratio = 1.02; 95% CI, 0.94-1.11; P = .56) and without (risk ratio = 1.03; 95% CI, 0.95-1.12; P = .52) studies with double-zero events revealed robust effect size estimates. Sensitivity analysis with studies judged at low risk for selection bias showed similar results. Administration of TXA was associated with a significant reduction in overall mortality and bleeding mortality but not with nonbleeding mortality. In addition, an increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism. Comparison of studies with sample sizes of less than or equal to 99 (risk difference = 0.004; 95% CI, -0.006 to 0.014; P = .40), 100 to 999 (risk difference = 0.004; 95% CI, -0.003 to 0.011; P = .26), and greater than or equal to 1000 (risk difference = -0.001; 95% CI, -0.003 to 0.001; P = .44) showed no association between TXA and incidence of total TEs. Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs (risk difference, -0.005; 95% CI, -0.021 to 0.011; P = .53).Conclusions and relevanceFindings from this systematic review and meta-analysis of 216 studies suggested that intravenous TXA, irrespective of dosing, is not associated with increased risk of any TE. These results help clarify the incidence of adverse events associated with administration of intravenous TXA and suggest that TXA is safe for use with undetermined utility for patients receiving neurological care.
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Project description:Background/purposeTranexamic acid (TA) is one of the commonly used local hemostatic agents for dental procedures and a previous study has demonstrated a significantly lower incidence of post-procedural bleeding (PPB) in patients taking warfarin and received local TA treatment after the dental procedures than those who took warfarin and did not receive local TA treatment. However, it is still unknown whether post-procedural local TA treatment can lower the bleeding risk to the same level as individuals who do not take oral anticoagulant (OAC). The current study aimed to compare the PPB risk in patients who took OAC and received local TA treatment after the dental procedures and individuals who did not take OAC and underwent similar dental procedures.Materials and methodsWe systematically searched primary researches from two databases and four eligible cohort studies were identified. The bleeding incidence was collected from each study and the pooled odds ratio (OR) and 95% confidence interval (CI) of PPB were calculated using Mantel-Haenzel method.ResultsThe analysis revealed a higher risk of PPB in patients who took OAC and received local TA treatment after the dental procedures than individuals who did not take OAC and underwent similar dental procedures with the pooled OR of 2.4, although the pooled effect estimate had a relatively wide 95% CI with non-statistically difference (0.69-8.12).ConclusionThis study results serve as a reminder to dentists that the increased risk of PPB in those who took OAC is not entirely resolved by the local TA treatment.
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Project description:ImportanceEvidence has emerged on the efficacy of tranexamic acid to control blood loss and postoperative complications after rhinoplasty.ObjectiveTo investigate the results of tranexamic acid use to reduce intraoperative bleeding, postoperative eyelid edema, and periorbital ecchymosis in rhinoplasty.Data sources and study selectionFor this systematic review of randomized clinical trials, searches were performed in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, Science Direct, Google Scholar, OpenThesis, and ClinicalTrials.gov from inception to December 23, 2017. Key words included tranexamic acid, rhinoplasty, and nasal surgical procedures. The following elements were used to define eligibility criteria: (1) population: patients undergoing rhinoplasty surgery; (2) intervention and controls: tranexamic acid vs placebo solution or no-treatment control group; (3) outcomes: intraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis, and thromboembolic events; and (4) study type: randomized clinical trials.Data extraction and synthesisTwo reviewers extracted data and assessed study quality according to the Cochrane guidelines for randomized clinical trials. Treatment effects were defined as weighted mean difference (WMD) and 95% CIs. The strength of evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation rating system.Main outcomes and measuresIntraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis. To calculate the effect sizes, means and SDs were obtained for each study group and outcome of interest.ResultsFive studies comprising 276 patients were included in the systematic review: 177 patients (64.1%) were women, and mean age was 26.8 (range, 16-42) years. Four studies comprising 246 patients estimated the amount in intraoperative bleeding as a primary outcome and were included in the meta-analysis. Eyelid edema and ecchymosis were evaluated as outcomes in 2 studies. Tranexamic acid was associated with reduced bleeding during rhinoplasty was found (WMD, -42.28 mL; 95% CI, -70.36 to -14.21 mL), with differences (P?=?.01) between oral (WMD, -61.70 mL; 95%?CI, -83.02 to -40.39 mL; I2?=?0%) and intravenous (WMD, -23.88 mL; 95% CI, -45.19 to -2.58 mL; I2?=?56%) administration. Eyelid edema and ecchymosis scores in patients receiving tranexamic acid were significantly lower compared with the control group within the first postoperative week: lower eyelid edema, WMD, -0.76; 95% CI, -1.04 to -0.49 and lower eyelid ecchymosis, WMD, -0.94; 95% CI, -1.80 to -0.08. No cases of thromboembolic events were reported.Conclusions and relevanceCurrent available evidence suggests that preoperative administration of tranexamic acid is safe and may reduce intraoperative bleeding as well as postoperative eyelid edema and ecchymosis in patients undergoing rhinoplasty.
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Project description:Tranexamic acid (TXA) is an antifibrinolytic agent that has been shown to decrease blood loss and transfusion rates after knee and hip arthroplasty, however with only limited evidence to support its use in shoulder arthroplasty. Therefore, we performed a systematic review and meta-analysis to evaluate the clinical usefulness of tranexamic acid for shoulder arthroplasty. A thorough literature search was conducted across four electronic databases (PubMed, Cochrane Library, Web of Science, Scopus) from inception through to 1 December 2021. The mean difference (MD), odds ratio (OR) or relative risk (RR) and 95% confidence interval (CI) were used to estimate pooled results from studies. Total of 10 studies comprising of 993 patients met the inclusion criteria and were included in the analysis. Blood volume loss in the TXA and non-TXA group was 0.66 ± 0.52 vs. 0.834 ± 0.592 L (MD= -0.15; 95%CI: -0.23 to -0.07; p < 0.001). Change of hemoglobin levels were 2.2 ± 1.0 for TXA group compared to 2.7 ± 1.1 for non-TXA group (MD= -0.51; 95%CI: -0.57 to -0.44; p < 0.001) and hematocrit change was 6.1 ± 2.7% vs. 7.9 ± 3.1%, respectively; (MD= -1.43; 95%CI: -2.27 to -0.59; p < 0.001). Tranexamic acid use for shoulder arthroplasty reduces blood volume loss during and after surgery and reduces drain output and hematocrit change.
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Project description:It is unclear how tranexamic acid (TXA) affects blood loss and seizures in meningioma resections. We performed a systematic review and meta-analysis and tried to evaluate the effectiveness and safety of TXA use for patients undergoing meningioma resections. Regards to this systematic review and meta-analysis (registered with CRD42023416693), we searched PubMed, Embase (Ovid), EBSCO, and Cochrane central library up to and including Oct 2023. Patients undergoing meningioma resections treated with TXA and placebo or no treatment were eligible for this study. This would allow delineation of the impact of TXA on blood loss, postoperative seizure, and other complication incidences. Four prospective cohort studies with 781 patients (390 patients in the TXA group and 391 patients in the control group) were conducted via a systematic review and meta-analysis. The results suggested that the application of TXA for patients undergoing meningioma resections reduced mean blood loss of 252 mL with 95% confidence interval (CI) -469.26 to -34.67 (P = 0.02) and I2 of 94% but did not increase postoperative seizure (risk ratio: 1.08; 95%CI: 0.54 to 2.15; P = 0.84) and other complication rates. This systematic review and meta-analysis suggests that the administration of TXA could reduce blood loss in patients undergoing intracerebral meningioma resection. The systematic review protocol has been registered at PROSPERO (Registration No. CRD42023416693) on April 23, 2023.
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Project description:The antifibrinolytic agent tranexamic acid (TXA) has demonstrated clinical benefit in trauma patients with severe bleeding, but its effectiveness in patients with traumatic brain injury (TBI) is unclear. We conducted a systematic review to evaluate the following research question: In ED patients with or at risk of intracranial hemorrhage (ICH) secondary to TBI, does TXA compared to placebo improve patients' outcomes?MEDLINE, EMBASE, CINAHL, and other databases were searched for randomized controlled trial (RCT) or quasi-RCT studies that compared the effect of TXA to placebo on outcomes of TBI patients. The main outcomes of interest included mortality, neurologic function, hematoma expansion, and adverse effects. We used "Grading quality of evidence and strength of recommendations" to assess the quality of trials. Two authors independently abstracted data using a data collection form. Results from studies were pooled when appropriate.Of 1030 references identified through the search, 2 high-quality RCTs met inclusion criteria. The effect of TXA on mortality had a pooled relative risk of 0.64 (95% confidence interval [CI], 0.41-1.02); on unfavorable functional status, a relative risk of 0.77 (95% CI, 0.59-1.02); and on ICH progression, a relative risk of 0.76 (95% CI, 0.58-0.98). No serious adverse effects (such as thromboembolic events) associated with TXA group were reported in the included trials.Pooled results from the 2 RCTs demonstrated statistically significant reduction in ICH progression with TXA and a nonstatistically significant improvement of clinical outcomes in ED patients with TBI. Further evidence is required to support its routine use in patients with TBI.
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Project description:IntroductionBleeding during cardiac surgery is associated with increased morbidity and mortality. Tranexamic acid is an antifibrinolytic with proven efficacy in major surgeries. Current clinical practice guidelines recommend intraoperative use in cardiac procedures. However, several complications have been reported with tranexamic acid including seizures. This review intends to summarise the evidence examining the efficacy and safety of tranexamic acid in patients undergoing cardiac surgery.Methods/designWe will search MEDLINE, Embase, PubMED, ACPJC, CINAHL and the Cochrane trial registry for eligible randomised controlled trials, the search dates for all databases will be from inception until 1 January 2019, investigating the perioperative use of topical and/or intravenous tranexamic acid as a stand-alone antifibrinolytic agent compared with placebo in patients undergoing open cardiac surgery. We categorised outcomes as patient critical or patient important. Selected patient-critical outcomes are: mortality (intensive care unit, hospital and 30-day endpoints), reoperation within 24 hours, postoperative bleeding requiring transfusion of packed red blood cells, myocardial infarction, stroke, pulmonary embolism, bowel infarction, upper or lower limb deep vein thrombosis and seizures. Those outcomes, we perceived as clinical experts to be most patient valued and patients were not involved in outcomes selection process. We will not apply publication date, language, journal or methodological quality restrictions. Two reviewers will independently screen and identify eligible studies using predefined eligibility criteria and then review full reports of all potentially relevant citations. A third reviewer will resolve disagreements if consensus cannot be achieved. We will present the results as relative risk with 95% CIs for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CIs. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication TRIAL REGISTRATION NUMBER: CRD42018105904.
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