title: Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.
abstract: There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.
  
  
  
  The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).
  
  
  
  We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.
  
  
  
  We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.
  
  
  
  We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.
  
  
  
  A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).
  
  
  
  Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.
authors.affiliation: Division of General Internal Medicine, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, New Jersey, USA, 08903.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Carson
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Stanworth
authors.forename: Nareg
authors.initials: N
authors.lastname: Roubinian
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fergusson
authors.forename: Darrell
authors.initials: D
authors.lastname: Triulzi
authors.forename: Carolyn
authors.initials: C
authors.lastname: Doree
authors.forename: Paul C
authors.initials: PC
authors.lastname: Hebert
mesh_terms: D000740:Anemia / Q000097:blood / Q000628:therapy; D017707:Erythrocyte Transfusion / Q000009:adverse effects / Q000401:mortality / Q000592:standards* / Q000706:statistics & numerical data; D006400:Hematocrit / Q000592:standards; D006441:Hemoglobin A / Q000032:analysis / Q000592:standards*; D006801:Humans; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D014182:Transplantation, Autologous / Q000592:standards; D014184:Transplantation, Homologous / Q000401:mortality / Q000592:standards
chemical_list: D006441:Hemoglobin A