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NIHR Signal Transfusing blood close to its use-by date does not increase deaths in critically ill adults

Published on 19 December 2017

doi: 10.3310/signal-000524

Transfusing more recently-collected red blood cells does not improve the chance of survival for critically-ill people who need blood transfusions, compared with blood that has been stored for longer.

This large international study included almost 5,000 critically ill people in intensive care units. Participants were transfused with either the freshest compatible blood available (mean storage 11.8 days) or the oldest compatible stored blood within its use-by date (mean storage time 22.4 days).

There was no difference in deaths between the two groups. Almost a quarter of people died in each group by 90 days. There were also no differences in other outcomes such as length of stay in intensive care.

This provides strong evidence to support the practice of transfusing the oldest compatible red blood cells to minimise waste of precious and costly blood stocks when they become out-of-date. In the UK, this is up to 35 days from donation.

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Why was this study needed?

Transfusions of red blood cells into critically-ill patients are common. Most hospitals around the world use the oldest stored blood within the use-by date, to make the most efficient use of stored blood products and minimise waste. However, concerns have been raised about whether blood that has been stored for longer could have less benefit and evidence from older studies has been inconsistent.

A recent randomised controlled trial (ABLE) found no association between age of red blood cells and chances of survival after 90 days. ABLE was smaller (2,430 adults) than the current study and compared red blood stored for seven days or less with older blood. Notably, ABLE also found no difference in cost between the use of older and newer blood.

This study aimed to compare usual practice with freshest-available blood.

What did this study do?

Researchers for the TRANSFUSE study carried out a double-blinded randomised controlled trial. They randomised 4,994 critically-ill participants from 59 intensive care centres in five countries (Australia, New Zealand, Ireland, Finland and Saudi Arabia) who had been prescribed red blood transfusions. Participants were assigned to either freshest available compatible red blood cells or oldest available compatible red blood cells.

Researchers followed up participants for 180 days. The main outcome was death after 90 days, although they also looked at death after 28 days, blood infection, and other secondary outcomes.

The study was robust and strengthens the evidence on this topic.

What did it find?

  • Participants were equally likely to have died by 90 days after randomisation, whether they had fresher blood (610 of 2,457 patients, 24.8%) or longer-stored blood (594 of 2,462 patients, 24.1%). The absolute risk difference of 0.7% was not statistically significant (95% confidence interval [CI] -1.7 to 3.1).
  • Similar results were shown after 180 days with 687 (28.5%) deaths following fresher blood and 678 (28.1%) after longer-stored blood, (absolute risk difference 0.4%, 95% CI ‑2.1 to 3.0).
  • There was no difference between the two groups for death after 28 days, length of stay in intensive care, bloodstream infections or organ support including use of mechanical ventilation or renal replacement therapy.

What does current guidance say on this issue?

Guidelines from the Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee govern the preparation and storage of blood products in the UK.

A minimum of 75% of red cells is expected to survive 24 hours after transfusion and the guidelines state that red blood cells can be used for up to 35 days. The guidelines do not state whether fresher or older blood products should be used first, however.

What are the implications?

The study findings suggest that hospital intensive care and emergency departments can use the oldest compatible stored blood, within storage guidelines, when supplying red blood cells for transfusion into critically ill adults.

This practice should allow them to make the most efficient use of donated blood, with as little as possible going to waste because they pass the use-by-date.

Citation and Funding

Cooper DJ, McQuilten ZK, Nichol A, et al.; TRANSFUSE Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Age of red cells for transfusion and outcomes in critically ill adults. N Engl J Med. 2017;377:1858-67.

The study was funded by grants from the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, the Irish Health Research Board and the Australian Red Cross Blood Service.

Why was this study needed?

Transfusions of red blood cells into critically-ill patients are common. Most hospitals around the world use the oldest stored blood within the use-by date, to make the most efficient use of stored blood products and minimise waste. However, concerns have been raised about whether blood that has been stored for longer could have less benefit and evidence from older studies has been inconsistent.

A recent randomised controlled trial (ABLE) found no association between age of red blood cells and chances of survival after 90 days. ABLE was smaller (2,430 adults) than the current study and compared red blood stored for seven days or less with older blood. Notably, ABLE also found no difference in cost between the use of older and newer blood.

This study aimed to compare usual practice with freshest-available blood.

What did this study do?

Researchers for the TRANSFUSE study carried out a double-blinded randomised controlled trial. They randomised 4,994 critically-ill participants from 59 intensive care centres in five countries (Australia, New Zealand, Ireland, Finland and Saudi Arabia) who had been prescribed red blood transfusions. Participants were assigned to either freshest available compatible red blood cells or oldest available compatible red blood cells.

Researchers followed up participants for 180 days. The main outcome was death after 90 days, although they also looked at death after 28 days, blood infection, and other secondary outcomes.

The study was robust and strengthens the evidence on this topic.

What did it find?

  • Participants were equally likely to have died by 90 days after randomisation, whether they had fresher blood (610 of 2,457 patients, 24.8%) or longer-stored blood (594 of 2,462 patients, 24.1%). The absolute risk difference of 0.7% was not statistically significant (95% confidence interval [CI] -1.7 to 3.1).
  • Similar results were shown after 180 days with 687 (28.5%) deaths following fresher blood and 678 (28.1%) after longer-stored blood, (absolute risk difference 0.4%, 95% CI ‑2.1 to 3.0).
  • There was no difference between the two groups for death after 28 days, length of stay in intensive care, bloodstream infections or organ support including use of mechanical ventilation or renal replacement therapy.

What does current guidance say on this issue?

Guidelines from the Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee govern the preparation and storage of blood products in the UK.

A minimum of 75% of red cells is expected to survive 24 hours after transfusion and the guidelines state that red blood cells can be used for up to 35 days. The guidelines do not state whether fresher or older blood products should be used first, however.

What are the implications?

The study findings suggest that hospital intensive care and emergency departments can use the oldest compatible stored blood, within storage guidelines, when supplying red blood cells for transfusion into critically ill adults.

This practice should allow them to make the most efficient use of donated blood, with as little as possible going to waste because they pass the use-by-date.

Citation and Funding

Cooper DJ, McQuilten ZK, Nichol A, et al.; TRANSFUSE Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Age of red cells for transfusion and outcomes in critically ill adults. N Engl J Med. 2017;377:1858-67.

The study was funded by grants from the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, the Irish Health Research Board and the Australian Red Cross Blood Service.

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults

Published on 28 September 2017

Cooper, D. J.,McQuilten, Z. K.,Nichol, A.,Ady, B.,Aubron, C.,Bailey, M.,Bellomo, R.,Gantner, D.,Irving, D. O.,Kaukonen, K. M.,McArthur, C.,Murray, L.,Pettila, V.,French, C.

N Engl J Med , 2017

Background It is uncertain whether the duration of red-cell storage affects mortality after transfusion among critically ill adults. Methods In an international, multicenter, randomized, double-blind trial, we assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells (short-term storage group) or standard-issue (oldest available), compatible, allogeneic red cells (long-term storage group). The primary outcome was 90-day mortality. Results From November 2012 through December 2016, at 59 centers in five countries, 4994 patients underwent randomization and 4919 (98.5%) were included in the primary analysis. Among the 2457 patients in the short-term storage group, the mean storage duration was 11.8 days. Among the 2462 patients in the long-term storage group, the mean storage duration was 22.4 days. At 90 days, there were 610 deaths (24.8%) in the short-term storage group and 594 (24.1%) in the long-term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], -1.7 to 3.1; P=0.57). At 180 days, the absolute risk difference was 0.4 percentage points (95% CI, -2.1 to 3.0; P=0.75). Most of the prespecified secondary measures showed no significant between-group differences in outcome. Conclusions The age of transfused red cells did not affect 90-day mortality among critically ill adults. (Funded by the Australian National Health and Medical Research Council and others; TRANSFUSE Australian and New Zealand Clinical Trials Registry number, ACTRN12612000453886 ; ClinicalTrials.gov number, NCT01638416 .).

Expert commentary

The safety of transfusions of stored red blood cell units has been controversial since the publication of a large observational study in 2008. It reported transfusions of ‘older’ red blood cells stored for more than two weeks were associated with more postoperative complications and increased mortality than red blood cells stored for less than two weeks.

Since then, more than ten randomised controlled trials in several clinical scenarios have not demonstrated any difference in mortality of transfusion of older red blood cells. The recently reported international multicentre TRANSFUSE trial in critical care patients confirms that finding, supporting the common practice of selecting the oldest red blood cells for transfusion to minimise outdating.

Mike F Murphy, Professor of Blood Transfusion Medicine, University of Oxford; Consultant Haematologist, NHS Blood & Transplant & Oxford University Hospitals NHS Foundation Trust