Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Blood transfusions are a very common medical procedure, and it's important to balance the potential benefits and harms. In December 2021, Jeffrey Carson from Rutgers Robert Wood Johnson Medical School, in New Brunswick in the USA, and colleagues updated the Cochrane Review of research comparing different triggers for transfusing red blood cells and we asked him to tell us more about the importance of the review and its findings.

Jeff: Patients who are ill in hospital are frequently anaemic, with low haemoglobin concentrations. The causes of anaemia are diverse, including blood loss during surgery, excessive blood sampling for laboratory tests, and the consequences of some illnesses. Anaemia decreases the oxygen content of the blood supplied to the tissues and makes the heart work harder to deliver oxygen around the body. However, it doesn't necessarily follow that correcting anaemia by the transfusion of red blood cells will improve outcomes. Anaemia is generally well tolerated by many people, and therefore, the benefits of red cell transfusions need to be weighed against the potential harms. 
Although the main option for raising haemoglobin concentration rapidly in anaemia is red blood cell transfusion, its availability and the potential harms vary throughout the world. In countries with well-regulated blood supplies, the safety of transfusion has improved significantly over recent decades, and the overall risks are very low. However, in resource-poor countries, blood transfusion is expensive, the supply of blood is inadequate, and the blood may not be safe because it is not often tested for viral pathogens. 
There are many randomized trials comparing different policies or schedules of using red cell transfusions. For instance, studies have randomised participants to 'restrictive' triggers (typically, they are transfused only when their haemoglobin concentration falls to around 7 g/ dL to 8 g/dL) versus 'liberal' triggers when they are transfused at a higher haemoglobin concentration of around 9 g/dL to 10 g/dL. 
Our review brings together the evidence from these trials. We are particularly interested in whether this supports the trend for increasingly restrictive transfusion practices across all patient groups and if transfusions can be withheld in some circumstances without harming patients. Since the last version of the review in 2016, several additional trials have become available, making it important to update the review, to ensure that guidelines continue to be based on the most recent literature. The number of trials has increased to 48, and the number of participants in these trials has nearly doubled to more 21,000.
Our review compares 30-day mortality and other clinical outcomes for restrictive versus liberal red blood cell transfusion thresholds for all conditions. We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin or haematocrit level below which a red blood cell transfusion was to be administered.
Of the 48 included studies, 11 are in orthopaedic surgery, eight in cardiac surgery, eight in cancer, leukemia, and hematological malignancies, seven in critical care, six in acute blood loss or trauma, three in acute coronary syndrome, and five in a variety of other conditions. The most common restrictive haemoglobin threshold was between 7.0 g/dL and 8.0 g/dL, in 35 trials, while the other trials used a threshold of 8 g/dL to 9.7 g/dL.
When we examined the impact of restrictive transfusion strategies on transfusion frequency, we found that it reduced the risk of receiving a transfusion by 41% across a broad range of clinical contexts but there was wide variability in the results of the individual trials. Looking at other outcomes, overall, restrictive transfusion strategies did not increase or decrease 30-day mortality compared with liberal strategies and we also found no important differences for cardiovascular outcomes such as cardiac events, myocardial infarction, stroke and thromboembolism; or infections.
However, there were insufficient data relating to the safety of transfusion policies in some clinical subgroups, including patients with acute coronary syndrome, chronic cardiovascular disease, vascular disease, hematological malignancies, acute neurological disorders, and chronic forms of anemia. Another limitation in the evidence is that haemoglobin concentration may not be the most informative marker of the need for transfusion in individual patients with different degrees of physiological adaptation to anaemia. 
In summary, restrictive transfusion reduced frequency of transfusion without harming the patients, when compared to liberal transfusion in a broad range of medical disorders. This is good evidence that transfusions with red blood cells can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.

Mike: If you would like to read more about these findings, the review is available online. Just go to Cochrane Library dot com and run a simple search for 'transfusion thresholds'.