Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion
Abstract
Background
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.
Objectives
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).
Search methods
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.
Selection criteria
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.
Data collection and analysis
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'.
Main results
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).
Authors' conclusions
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.
PICOs
Plain language summary
Is it safe to use lower blood counts as a trigger for blood transfusion in order to give fewer blood transfusions?
Background
Doctors and healthcare professionals often give blood transfusions to people after loss of blood from surgery, bleeding, or medical illnesses. Blood is a limited resource, so for this reason, and because some low‐income countries do not test the blood used in transfusions for the presence of dangerous viruses such as HIV or hepatitis, it is helpful to give blood transfusions only when they are really necessary.
A normal blood count is above 12. This review summarised all randomized controlled trials (RCTs) that investigated whether it is safe to give blood transfusions when the blood count drops to between seven and eight (thereby reducing the number of transfusions), rather than giving transfusions at higher blood counts of nine to 10.
Study characteristics
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.
Key results
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.
Quality of evidence
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.
Authors conclusions
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.
