Dataset Information

Safety of tranexamic acid in thrombotic adverse events and seizure in patients with haemorrhage: a protocol for a systematic review and meta-analysis.

ABSTRACT:

Introduction

Tranexamic 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 analysis

We 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 dissemination

This 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 number

UMIN000039611.

SUBMITTER: Murao S

PROVIDER: S-EPMC7311044 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety of tranexamic acid in thrombotic adverse events and seizure in patients with haemorrhage: a protocol for a systematic review and meta-analysis.

Murao Shuhei S Nakata Hidekazu H Yamakawa Kazuma K

BMJ open 20200622 6

<h4>Introduction</h4>Tranexamic 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.<h4>Methods and analysis</h4>We will conduct a systematic review and meta-ana ...[more]

PMID: 32571860

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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.

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.

Dataset Information

Safety of tranexamic acid in thrombotic adverse events and seizure in patients with haemorrhage: a protocol for a systematic review and meta-analysis.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Safety of tranexamic acid in thrombotic adverse events and seizure in patients with haemorrhage: a protocol for a systematic review and meta-analysis.

Similar Datasets

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