John: Blood transfusions are a very common medical procedure, and it’s important to balance the potential benefits and harms. In October 2016, Jeffery 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. It has been associated with worse outcomes in patients who are anaemic before surgery or who have cardiovascular disease. 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 the past 30 years, 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 were particularly interested in whether the results support 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 review in 2012, the number of relevant trials has increased, such that the number of participants in these studies has doubled to more 12,500. This made it important to update the review, to ensure that guidelines continue to be based on the most recent literature.
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.
Thirty-one studies were eligible for inclusion. There were ten trial in orthopaedic surgery, six in critical care, five in acute blood loss or trauma, five in cardiac surgery and smaller numbers in a variety of other conditions. The tested strategies were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half the trials used a 7 g/dL threshold, while the others used a restrictive transfusion threshold of 8 g/dL to 9 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 43% across a broad range of clinical specialties participants. Overall, restrictive transfusion strategies did not increase or decrease 30-day mortality compared with liberal transfusion strategies; and the results were little different when we divided the trials on the basis of the restrictive transfusion threshold. We also found no increase in risk from liberal or restrictive transfusion for outcomes such as cardiac events, myocardial infarction, stroke, and thromboembolism; or for infections like pneumonia, wound infection, and bacteraemia.
However, there were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, acute neurological disorders, and patients with chronic forms of anemia.
In summary, restrictive transfusion reduced frequency of transfusion without harming the patients, compared to liberal transfusion in a broad range of medical disorders. Our findings provide 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.

John: If you would like to read more about the thresholds that have been used, and the review’s detailed findings for many clinical outcomes, go to Cochrane Library dot com, and search simply for ‘transfusion thresholds’.