title: Topical application of tranexamic acid for the reduction of bleeding.
abstract: BACKGROUND
  Intravenous tranexamic acid reduces bleeding in surgery, however, its effect on the risk of thromboembolic events is uncertain and an increased risk remains a theoretical concern. Because there is less systemic absorption following topical administration, the direct application of tranexamic acid to the bleeding surface has the potential to reduce bleeding with minimal systemic effects.
  
  
  OBJECTIVE
  To assess the effects of the topical administration of tranexamic acid in the control of bleeding.
  
  
  METHODS
  We searched the Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily and Ovid OLDMEDLINE®; Embase Classic + Embase (OvidSP); PubMed and ISI Web of Science (including Science Citation Index Expanded and Social Science Citation Index (SCI-EXPANDED & CPCI-S)). We also searched online trials registers to identify ongoing or unpublished trials. The search was run on the 31st May 2013.
  
  
  METHODS
  Randomised controlled trials comparing topical tranexamic acid with no topical tranexamic acid or placebo in bleeding patients.
  
  
  METHODS
  Two authors examined the titles and abstracts of citations from the electronic databases for eligibility. Two authors extracted the data and assessed the risk of bias for each trial. Outcome measures of interest were blood loss, mortality, thromboembolic events (myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism) and receipt of a blood transfusion.
  
  
  RESULTS
  We included 29 trials involving 2612 participants. Twenty-eight trials involved patients undergoing surgery and one trial involved patients with epistaxis (nosebleed). Tranexamic acid (TXA) reduced blood loss by 29% (pooled ratio 0.71, 95% confidence interval (CI) 0.69 to 0.72; P < 0.0001). There was uncertainty regarding the effect on death (risk ratio (RR) 0.28, 95% CI 0.06 to 1.34; P = 0.11), myocardial infarction (RR 0.33, 95% CI 0.04 to 3.08; P = 0.33), stroke (RR 0.33, 95% CI 0.01 to 7.96; P = 0.49), deep vein thrombosis (RR 0.69, 95% CI 0.31 to 1.57; P = 0.38) and pulmonary embolism (RR 0.52, 95% CI 0.09 to 3.15; P = 0.48). TXA reduced the risk of receiving a blood transfusion by a relative 45% (RR 0.55, 95% CI 0.55 to 0.46; P < 0.0001). There was substantial statistical heterogeneity between trials for the blood loss and blood transfusion outcomes.
  
  
  CONCLUSIONS
  There is reliable evidence that topical application of tranexamic acid reduces bleeding and blood transfusion in surgical patients, however the effect on the risk of thromboembolic events is uncertain. The effects of topical tranexamic acid in patients with bleeding from non-surgical causes has yet to be reliably assessed. Further high-quality trials are warranted to resolve these uncertainties before topical tranexamic acid can be recommended for routine use.
authors.affiliation: Cochrane Injuries Group, London School of Hygiene & Tropical Medicine, London, UK. katharine.ker@lshtm.ac.uk.
authors.forename: Katharine
authors.initials: K
authors.lastname: Ker
authors.forename: Deirdre
authors.initials: D
authors.lastname: Beecher
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
mesh_terms: D000287:Administration, Topical; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D004844:Epistaxis / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014148:Tranexamic Acid / Q000008:administration & dosage*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid