Journal Article

Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis

Yamakawa, Kazuma, Murao, Shuhei, Roberts, Ian, Nakata, Hidekazu

2021

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acute Coronary Syndrome - epidemiology / Acute coronary syndromes / Antifibrinolytic agents / Antifibrinolytic Agents - adverse effects / Bias / Binding sites / Bleeding / Blood clot / Bone surgery / Critical care / Critical Care Medicine / Drug therapy / Emergency Medicine / Gynecology / Health aspects / Heart surgery / Hemorrhage / Hemorrhage - drug therapy / Humans / Intensive / Intervention / Medicine / Medicine & Public Health / Meta-analysis / Methods / Obstetrics / Orthopedics / Regression analysis / Risk Assessment / Risk factors / Seizure / Seizures (Medicine) / Seizures - epidemiology / Software / Stroke / Stroke - epidemiology / Surgery / Systematic review / Thromboembolism / Thrombosis / Thrombotic events / Tranexamic acid / Tranexamic Acid - adverse effects / Transient ischemic attack / Trauma / Treatment Outcome / Venous Thromboembolism - epidemiology