title: Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis.
abstract: OBJECTIVE
  To assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Cochrane 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.
  
  
  METHODS
  Randomised 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.
  
  
  RESULTS
  129 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.
  
  
  CONCLUSIONS
  Strong 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.
authors.affiliation: Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. katharine.ker@lshtm.ac.uk
authors.forename: Katharine
authors.initials: K
authors.lastname: Ker
authors.forename: Phil
authors.initials: P
authors.lastname: Edwards
authors.forename: Pablo
authors.initials: P
authors.lastname: Perel
authors.forename: Haleema
authors.initials: H
authors.lastname: Shakur
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
mesh_terms: D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000401:mortality / Q000517:prevention & control*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000453:epidemiology; D013923:Thromboembolism / Q000453:epidemiology; D014148:Tranexamic Acid / Q000627:therapeutic use*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid