Health Care–Associated Infection After Red Blood Cell Transfusion: A Systematic Review and Meta-analysis | Health Care Safety | JAMA | JAMA Network
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US Department of Health and Human Services.  National action plan to prevent healthcare-associated infections: roadmap to elimination. Accessed February 4, 2014.
Pronovost  P, Needham  D, Berenholtz  S,  et al.  An intervention to decrease catheter-related bloodstream infections in the ICU.  N Engl J Med. 2006;355(26):2725-2732.PubMedGoogle ScholarCrossref
Boyce  JM, Pittet  D; Healthcare Infection Control Practices Advisory Committee; HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force; Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America.  Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.  MMWR Recomm Rep. 2002;51(RR-16):1-45.PubMedGoogle Scholar
Saint  S, Greene  MT, Kowalski  CP, Watson  SR, Hofer  TP, Krein  SL.  Preventing catheter-associated urinary tract infection in the United States: a national comparative study.  JAMA Intern Med. 2013;173(10):874-879.PubMedGoogle ScholarCrossref
Scott  RD.  The direct medical costs of health care–associated infections in US hospitals and the benefits of prevention. Accessed February 4, 2014.
Whitaker  BI, Hinkins  S.  The 2011 national blood collection and utilization survey. Accessed 2/5/2014.
Lannan  KL, Sahler  J, Spinelli  SL, Phipps  RP, Blumberg  N.  Transfusion immunomodulation—the case for leukoreduced and (perhaps) washed transfusions.  Blood Cells Mol Dis. 2013;50(1):61-68.PubMedGoogle ScholarCrossref
Buddeberg  F, Schimmer  BB, Spahn  DR.  Transfusion-transmissible infections and transfusion-related immunomodulation.  Best Pract Res Clin Anaesthesiol. 2008;22(3):503-517.PubMedGoogle ScholarCrossref
Fergusson  D, Khanna  MP, Tinmouth  A, Hébert  PC.  Transfusion of leukoreduced red blood cells may decrease postoperative infections: 2 meta-analyses of randomized controlled trials.  Can J Anaesth. 2004;51(5):417-424.PubMedGoogle ScholarCrossref
Carson  JL, Brooks  MM, Abbott  JD,  et al.  Liberal vs restrictive transfusion thresholds for patients with symptomatic coronary artery disease.  Am Heart J. 2013;165(6):964-971, e1.PubMedGoogle ScholarCrossref
Villanueva  C, Colomo  A, Bosch  A,  et al.  Transfusion strategies for acute upper gastrointestinal bleeding.  N Engl J Med. 2013;368(1):11-21.PubMedGoogle ScholarCrossref
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  Ann Intern Med. 2009;151(4):264-269, W64.PubMedGoogle ScholarCrossref
Carson  JL, Carless  PA, Hebert  PC.  Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.  Cochrane Database Syst Rev. 2012;4:CD002042.PubMedGoogle Scholar
Gregersen  M, Borris  LC, Damsgaard  EM.  A liberal blood transfusion strategy after hip fracture surgery does not increase the risk of infection in frail elderly.  Eur Geriatr Med.2012;3 (supp 1):S74. doi:10.1016/j.eurger.2012.07.139Google ScholarCrossref
Freeman  MF, Tukey  JW.  Transformations related to the angular and the square root.  Ann Math Stat. 1950;21:607-611.Google ScholarCrossref
Kuhnert  R, Böhning  D.  A comparison of 3 different models for estimating relative risk in meta-analysis of clinical trials under unobserved heterogeneity.  Stat Med. 2007;26(11):2277-2296.PubMedGoogle ScholarCrossref
Hill  GE, Frawley  WH, Griffith  KE, Forestner  JE, Minei  JP.  Allogeneic blood transfusion increases the risk of postoperative bacterial infection: a meta-analysis.  J Trauma. 2003;54(5):908-914.PubMedGoogle ScholarCrossref
Rogers  MA, Blumberg  N, Saint  S, Langa  KM, Nallamothu  BK.  Hospital variation in transfusion and infection after cardiac surgery: a cohort study.  BMC Med. 2009;7:37.PubMedGoogle ScholarCrossref
Rogers  MA, Blumberg  N, Saint  SK, Kim  C, Nallamothu  BK, Langa  KM.  Allogeneic blood transfusions explain increased mortality in women after coronary artery bypass graft surgery.  Am Heart J. 2006;152(6):1028-1034.PubMedGoogle ScholarCrossref
Bracey  AW, Radovancevic  R, Riggs  SA,  et al.  Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.  Transfusion. 1999;39(10):1070-1077.PubMedGoogle ScholarCrossref
Hajjar  LA, Vincent  JL, Galas  FR,  et al.  Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.  JAMA. 2010;304(14):1559-1567.PubMedGoogle ScholarCrossref
Cholette  JM, Rubenstein  JS, Alfieris  GM, Powers  KS, Eaton  M, Lerner  NB.  Children with single-ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy.  Pediatr Crit Care Med. 2011;12(1):39-45.PubMedGoogle ScholarCrossref
Cooper  HA, Rao  SV, Greenberg  MD,  et al.  Conservative vs liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study).  Am J Cardiol. 2011;108(8):1108-1111.PubMedGoogle ScholarCrossref
Shehata  N, Burns  LA, Nathan  H,  et al.  A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery.  Transfusion. 2012;52(1):91-99.PubMedGoogle ScholarCrossref
de Gast-Bakker  DH, de Wilde  RB, Hazekamp  MG,  et al.  Safety and effects of 2 red blood cell transfusion strategies in pediatric cardiac surgery patients: a randomized controlled trial.  Intensive Care Med. 2013;39(11):2011-2019.PubMedGoogle ScholarCrossref
Hébert  PC, Wells  G, Blajchman  MA,  et al.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care: Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.  N Engl J Med. 1999;340(6):409-417.PubMedGoogle ScholarCrossref
LaCroix  J, Hébert  PC, Hutchison  JS,  et al; TRIPICU Investigators; Canadian Critical Care Trials Group; Pediatric Acute Lung Injury and Sepsis Investigators Network.  Transfusion strategies for patients in pediatric intensive care units.  N Engl J Med. 2007;356(16):1609-1619.PubMedGoogle ScholarCrossref
Kirpalani  H, Whyte  RK, Andersen  C,  et al.  The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) vs liberal (high) transfusion threshold for extremely low birth weight infants.  J Pediatr. 2006;149(3):301-307.PubMedGoogle ScholarCrossref
Carson  JL, Terrin  ML, Barton  FB,  et al.  A pilot randomized trial comparing symptomatic vs hemoglobin level–driven red blood cell transfusions following hip fracture.  Transfusion. 1998;38(6):522-529.PubMedGoogle ScholarCrossref
Grover  M, Talwalkar  S, Casbard  A,  et al.  Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty.  Vox Sang. 2006;90(2):105-112.PubMedGoogle ScholarCrossref
Foss  NB, Kristensen  MT, Jensen  PS, Palm  H, Krasheninnikoff  M, Kehlet  H.  The effects of liberal vs restrictive transfusion thresholds on ambulation after hip fracture surgery.  Transfusion. 2009;49(2):227-234.PubMedGoogle ScholarCrossref
So-Osman  C, Nelissen  R, Te Slaa  R, Coene  L, Brand  R, Brand  A.  A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells.  Vox Sang. 2010;98(1):56-64.PubMedGoogle ScholarCrossref
Carson  JL, Terrin  ML, Noveck  H,  et al; FOCUS Investigators.  Liberal or restrictive transfusion in high-risk patients after hip surgery.  N Engl J Med. 2011;365(26):2453-2462.PubMedGoogle ScholarCrossref
Prick  BW, Jansen  AJG, Steegers  EAP,  et al.  Transfusion policy after severe postpartum haemorrhage: a randomised non-inferiority trial [published online January 10, 2014].  BJOG. doi:10.1111/1471-0528.12531.Google Scholar
Karam  O, Tucci  M, Ducruet  T, Hume  HA, Lacroix  J, Gauvin  F; Canadian Critical Care Trials Group; PALISI Network.  Red blood cell transfusion thresholds in pediatric patients with sepsis.  Pediatr Crit Care Med. 2011;12(5):512-518.PubMedGoogle ScholarCrossref
Vichinsky  EP, Haberkern  CM, Neumayr  L,  et al; The Preoperative Transfusion in Sickle Cell Disease Study Group.  A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease.  N Engl J Med. 1995;333(4):206-213.PubMedGoogle ScholarCrossref
Howard  J, Malfroy  M, Llewelyn  C,  et al.  The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study: a randomised, controlled, multicentre clinical trial.  Lancet. 2013;381(9870):930-938.PubMedGoogle ScholarCrossref
So-Osman  C, Nelissen  R, Brand  R,  et al.  The impact of a restrictive transfusion trigger on post-operative complication rate and well-being following elective orthopaedic surgery: a post-hoc analysis of a randomised study.  Blood Transfus. 2013;11(2):289-295.PubMedGoogle Scholar
Horvath  KA, Acker  MA, Chang  H,  et al.  Blood transfusion and infection after cardiac surgery.  Ann Thorac Surg. 2013;95(6):2194-2201.PubMedGoogle ScholarCrossref
Carson  JL, Grossman  BJ, Kleinman  S,  et al; Clinical Transfusion Medicine Committee of the AABB.  Red blood cell transfusion: a clinical practice guideline from the AABB.  Ann Intern Med. 2012;157(1):49-58.PubMedGoogle ScholarCrossref
Centers for Disease Control and Prevention.  CDC/NHSN surveillance definitions for specific types of infections. Accessed February 5, 2014.
Wacker  C, Prkno  A, Brunkhorst  FM, Schlattmann  P.  Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis.  Lancet Infect Dis. 2013;13(5):426-435.PubMedGoogle ScholarCrossref
Original Investigation
April 2, 2014

Health Care–Associated Infection After Red Blood Cell Transfusion: A Systematic Review and Meta-analysis

Author Affiliations
  • 1University of Michigan, Division of General Medicine, Department of Internal Medicine, Ann Arbor
  • 2Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York
  • 3VA Ann Arbor Medical Center/University of Michigan Patient Safety Enhancement Program, Ann Arbor
  • 4VA Ann Arbor Health Services Research and Development Center of Excellence, Ann Arbor, Michigan
  • 5Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor
JAMA. 2014;311(13):1317-1326. doi:10.1001/jama.2014.2726

Importance  The association between red blood cell (RBC) transfusion strategies and health care–associated infection is not fully understood.

Objective  To evaluate whether RBC transfusion thresholds are associated with the risk of infection and whether risk is independent of leukocyte reduction.

Data Sources  MEDLINE, EMBASE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, Cochrane Database of Sytematic Reviews,, International Clinical Trials Registry, and the International Standard Randomized Controlled Trial Number register were searched through January 22, 2014.

Study Selection  Randomized clinical trials with restrictive vs liberal RBC transfusion strategies.

Data Extraction and Synthesis  Twenty randomized trials with 8598 patients met eligibility criteria, of which 17 trials (n = 7456 patients) contained sufficient information for meta-analyses. DerSimonian and Laird random-effects models were used to report pooled risk ratios. Absolute risks of infection were calculated using the profile likelihood random-effects method.

Main Outcomes and Measures  Incidence of health care–associated infection such as pneumonia, mediastinitis, wound infection, and sepsis.

Results  The pooled risk of all serious infections was 10.6% (95% CI, 5.6%-15.9%) in the restrictive group and 12.7% (95% CI, 7.0%-18.7%) in the liberal group. The risk ratio (RR) for the association between transfusion strategies and infection (serious infections and selected infections, combined) was 0.92 (95% CI, 0.82-1.04) with little heterogeneity (I2 = 6.3%; τ2 = .0041). The RR for the association between transfusion strategies and serious infection was 0.84 (95% CI, 0.73-0.96; I2 = 0%, τ2 <.0001). The number needed to treat (NNT) with restrictive strategies to prevent serious infection was 48 (95% CI, 36-71). The risk of infection remained reduced with a restrictive strategy, even with leukocyte reduction (RR, 0.83 [95% CI, 0.69-0.99]). For trials with a restrictive hemoglobin threshold of <7.0 g/dL, the RR was 0.86 (95% CI, 0.72-1.02). With stratification by patient type, the RR for serious infection was 0.72 (95% CI, 0.53-0.97) in patients undergoing orthopedic surgery and 0.51 (95% CI, 0.28-0.95) in patients presenting with sepsis. There were no significant differences in the incidence of infection by RBC threshold for patients with cardiac disease, the critically ill, those with acute upper gastrointestinal bleeding, or for infants with low birth weight.

Conclusions and Relevance  Among hospitalized patients, a restrictive RBC transfusion strategy compared with a liberal transfusion strategy was not associated with a reduced risk of health care–associated infection overall, although it was associated with a reduced risk of serious infection. Implementing restrictive strategies may have the potential to lower the incidence of serious health care–associated infection.