title: Changes in gene expression following trauma are related to the age of transfused packed red blood cells.
abstract: BACKGROUND
  Transfusion of packed red blood cells (PRBCs) is associated with an increased incidence of nosocomial infections and an increased risk of death. The duration of storage before transfusion may influence these outcomes. Here, we explore the association between the age of transfused PRBCs and specific patterns of inflammatory gene expression in severely injured trauma patients.
  
  
  METHODS
  Severely injured trauma patients requiring intensive care unit treatment and receiving transfusion of PRBCs within 24 hours of the injury were recruited. Blood samples were obtained within 2 hours of the trauma, at 24 hours, and at 72 hours. Messenger RNA was extracted from whole blood, and gene expression was quantified using quantitative polymerase chain reaction. The median age of the units of PRBCs transfused to each patient was recorded. The primary outcome measure was the change in candidate gene expression over the initial 72 hours.
  
  
  RESULTS
  Sixty-four patients were studied. Fifty-three patients (83%) were male, and the median age was 40.5 years (interquartile range [IQR], 31-59). Median Injury Severity Score (ISS) was 31.5 (IQR, 23-43), and 55 patients (86%) experienced a blunt injury. Forty-one patients (64%) developed a nosocomial infection, and 15 patients (23%) died before hospital discharge. Each patient received a median of 5 U of PRBCs (IQR, 4-9.8 U) during the first 24 hours of hospital admission. The median age of the units of PRBCs transfused in each patient was 20 days (IQR, 17-22 days). Older blood was associated with greater decreases in interleukin 12 (IL-12), IL-23, and RORγt (all p's < 0.05) gene expression over the initial 24 hours, greater decreases in IL-12 gene expression over 72 hours, and a rise in transforming growth factor β gene expression over the first 72 hours. A multivariate analysis confirmed the independence of these associations.
  
  
  CONCLUSIONS
  Increasing the duration of storage of PRBCs before transfusion is associated with a pattern of gene expression consistent with more severe immunosuppression.
  
  
  METHODS
  Epidemiologic study, level III.
authors.affiliation: From the Adult Critical Care Unit (H.D.T.T., M.E.V., J.R.P., R.M.P., C.J.H., M.J.O.), Royal London Hospital, Barts Health NHS Trust; Centre for Trauma Sciences (H.DT.T., K.B.), Blizard Institute, and Centre for Translational Medicine and Therapeutics (H.D.T.T., M.E.V., J.R.P., R.M.P., H.C.O., C.J.H., M.J.O.), William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Hew D T
authors.initials: HD
authors.lastname: Torrance
authors.forename: Mark E
authors.initials: ME
authors.lastname: Vivian
authors.forename: Karim
authors.initials: K
authors.lastname: Brohi
authors.forename: John R
authors.initials: JR
authors.lastname: Prowle
authors.forename: Rupert M
authors.initials: RM
authors.lastname: Pearse
authors.forename: Helen C
authors.initials: HC
authors.lastname: Owen
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Hinds
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Dwyer
mesh_terms: D000328:Adult; D001793:Blood Preservation / Q000009:adverse effects*; D003422:Critical Care; D016207:Cytokines / Q000235:genetics*; D017707:Erythrocyte Transfusion; D005260:Female; D015870:Gene Expression; D006801:Humans; D007165:Immunosuppression Therapy; D015601:Injury Severity Score; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D014157:Transcription Factors