title: Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial.
abstract: BACKGROUND
  The CRASH-2 trial showed that early administration of tranexamic acid (TXA) safely reduces mortality in bleeding in trauma patients. Based on data from the CRASH-2 trial, global mortality data and a systematic literature review, we estimated the number of premature deaths that might be averted every year worldwide through the use of TXA.
  
  
  METHODS
  We used CRASH-2 trial data to examine the effect of TXA on death due to bleeding by geographical region. We used WHO mortality data (2008) and data from a systematic review of the literature to estimate the annual number of in-hospital trauma deaths due to bleeding. We then used the relative risk estimates from the CRASH-2 trial to estimate the number of premature deaths that could be averted if all hospitalised bleeding trauma patients received TXA within one hour of injury, and within three hours of injury. Sensitivity analyses were used to explore the effect of uncertainty in the parameter estimates and the assumptions made in the model.
  
  
  RESULTS
  There is no evidence that the effect of TXA on death due to bleeding varies by geographical region (heterogeneity p = 0.70). Based on WHO data and our systematic literature review, we estimate that each year worldwide there are approximately 400,000 in-hospital trauma deaths due to bleeding. If patients received TXA within one hour of injury then approximately 128,000 (uncertainty range [UR] ≈ 72,000 to 172,000) deaths might be averted. If patients received TXA within three hours of injury then approximately 112,000 (UR ≈ 68,000 to 148,000) deaths might be averted. Country specific estimates show that the largest numbers of deaths averted would be in India and China.
  
  
  CONCLUSIONS
  The use of TXA in the treatment of traumatic bleeding has the potential to prevent many premature deaths every year. A large proportion of the potential health gains are in low and middle income countries.
authors.affiliation: Clinical Trials Unit, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. katharine.ker@lshtm.ac.uk
authors.forename: Katharine
authors.initials: K
authors.lastname: Ker
authors.forename: Junko
authors.initials: J
authors.lastname: Kiriya
authors.forename: Pablo
authors.initials: P
authors.lastname: Perel
authors.forename: Phil
authors.initials: P
authors.lastname: Edwards
authors.forename: Haleema
authors.initials: H
authors.lastname: Shakur
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D003710:Demography; D004638:Emergency Treatment; D014943:Global Health / Q000706:statistics & numerical data; D006801:Humans; D012307:Risk Factors; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000401:mortality; D014148:Tranexamic Acid / Q000008:administration & dosage*; D016896:Treatment Outcome; D014944:World Health Organization; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid