Abstract: 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.

Plain-language summary: We examined the results of RCTs that randomly allocated participants to one of two groups. In one group, trial participants received blood at lower blood counts. In the other group, trial participants received blood at higher blood counts. The data are current up to May 2016. We identified a total of 31 relevant trials, which involved 12,587 participants. All of the studies compared different policies for blood transfusions. We found that participants who were assigned to receive blood at lower blood counts were 43% less likely to receive a blood transfusion than those who were given blood at higher blood counts. The risk of dying within 30 days of the transfusion was the same whether the participants received transfusion at lower or higher blood counts. We also evaluated harmful events that occurred after participants received, or did not receive, blood transfusions, including infection (pneumonia, wound infection, and blood poisoning), heart attacks, strokes, and problems with blood clots, and found that there was no clear difference in the instance of these events between the group that received transfusions at lower blood counts and the group that received transfusions at higher blood counts. We found that most of the RCTs provided a high quality of evidence, in that they were adequately conducted and used appropriate methods that minimised any possible biases that could make the validity of the results uncertain. We concluded that it was not harmful to the participants' health status to give blood at lower or higher blood counts. If a policy of giving blood only at lower blood counts were followed routinely in clinical practice, it would reduce the amount of blood patients receive substantially and reduce the risk of patients receiving blood transfusions unnecessarily, as transfusions can have harmful effects. Additional studies are needed to establish the blood count at which a blood transfusion is needed in patients who have suffered a heart attack, brain injury, or have cancer.