title: Red blood cell transfusion and mortality in trauma patients: risk-stratified analysis of an observational study.
abstract: BACKGROUND
  Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death.
  
  
  RESULTS
  A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: <6%, 6%-20%, 21%-50%, and >50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction <0.0001). Transfusion was associated with an increase in all-cause mortality among patients with <6% and 6%-20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08-7.13, p<0.0001, and OR 2.31, 95% CI 1.96-2.73, p<0.0001, respectively), but with a decrease in all-cause mortality in patients with >50% predicted risk of death (OR 0.59, 95% CI 0.47-0.74, p<0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05-3.24, p<0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (<6%) predicted risk of death (p-value for interaction <0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar.
  
  
  CONCLUSIONS
  The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial.
  
  
  BACKGROUND
  www.ClinicalTrials.gov NCT01746953.
authors.affiliation: Epidemiology & Population Health Faculty, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perel
authors.affiliation: Epidemiology & Population Health Faculty, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Clayton
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Doug G
authors.initials: DG
authors.lastname: Altman
authors.affiliation: Arthritis Research UK Primary Care Centre, Keele University, Staffordshire, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Croft
authors.affiliation: Epidemiology & Population Health Faculty, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Douglas
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Harry
authors.initials: H
authors.lastname: Hemingway
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Aroon
authors.initials: A
authors.lastname: Hingorani
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom; School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Morley
authors.affiliation: School of Health and Population Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Riley
authors.affiliation: London Chest Hospital, London, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Timmis
authors.affiliation: Arthritis Research UK Primary Care Centre, Keele University, Staffordshire, United Kingdom.
authors.forename: Danielle
authors.initials: D
authors.lastname: Van der Windt
authors.affiliation: Epidemiology & Population Health Faculty, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
mesh_terms: D000328:Adult; D006801:Humans; D055815:Young Adult; D002423:Cause of Death; D017707:Erythrocyte Transfusion / Q000401:mortality; D006470:Hemorrhage / Q000401:mortality / Q000628:therapy; D016017:Odds Ratio; D012306:Risk; D018570:Risk Assessment; D014148:Tranexamic Acid / Q000627:therapeutic use; D014947:Wounds and Injuries / Q000401:mortality; D000094422:Secondary Data Analysis
chemical_list: D014148:Tranexamic Acid