The Fresher, the Better? How Does Age of Transfused Red Blood Cells Affect Patient Outcomes?

A meta-analysis of randomized clinical trials examining the effect of the age of transfused red blood cells (RBCs) on patient outcomes revealed that, when it comes to RBC transfusion, age is just a number. Transfusion with blood that had been stored for a longer period of time was not associated with an increase in death or adverse events (AEs) – but, paradoxically, was associated with a lower risk of infection – over “fresher” blood, according to the report by Paul E. Alexander, MHSc, MSc, from the Department of Clinical Epidemiology and Biostatistics at McMaster University in Hamilton, Ontario.

“Red blood cell transfusion is one of the most common medical treatments, with approximately 85 million red blood cell units transfused annually worldwide,” Dr. Alexander and co-authors wrote. “The impact of even a small risk could have significant patient impact globally.”

Longer storage of RBCs has been shown to lead to morphologic changes that could have a deleterious impact on oxygen delivery, including changes to the cell shape and membrane, an increase in adhesiveness, and a decline in flexibility that can hamper blood flow hemodynamics. The storage medium, as well, could generate superoxides and inflammatory mediators that could results in oxidative damage.

However, studies examining whether any benefit exists for transfusing fresher RBC are mostly uncontrolled and observational, Dr. Alexander and colleagues noted.

In this meta-analysis, the authors searched the literature for randomized clinical trials enrolling patients who were transfused with fresher versus older RBCs and reported on outcomes of death, AEs, and infection.

They identified 12 trials, which enrolled a total of 5,229 participants: six of these compared fresher RBCs with older RBCs, and the other six compared fresher RBCs with current standard practice. The definitions of “fresher” and “older” RBCs varied by study. Patients enrolled in these 12 trials were of varying ages with a range of medical and surgical conditions.

Three of these trials enrolled neonates and infants, one included patients ≥12 years old, and the remainder enrolled adults. Most trials enrolled patients experiencing acute critical illness and/or surgical hemorrhage.

“We found no benefit when fresher red blood cells were transfused as opposed to older/standard-issue red blood cells for either mortality or adverse events,” Dr. Alexander and colleagues concluded. “Results suggested that, if anything, fresher red blood cells might lead to an increase rather than a decrease in [hospital-acquired] infections.”

The risk of death (analyzed in all 12 trials) was similar in the fresher and older RBC groups (relative risk [RR] = 1.04; 95% CI 0.94-1.14; p=0.45).

Three trials reported transfusion-related AEs (including acute transfusion reactions, seizures, acute cardiac events, hepatobiliary events, and renal and urinary events). Again, there was no difference in AEs associated with age of RBC (RR=1.02; 95% CI 0.91-1.14; p=0.74).

Four trials reported on infections: one reported microbiologically confirmed infection, one reported clinical sepsis in neonates, and two reported clinically diagnosed infections. Interestingly, there was a 9 percent relative increase in the risk of infections in patients who received fresher RBCs (RR=1.09; 95% CI 1.00-1.18; p=0.04).

The varying definitions of “fresher” and “older” RBCs were one concern noted by Dr. Alexander, as was the variability in blood processing and storage methods. “Manipulations that increase red blood cell fragility, such as irradiation and washing, may exacerbate the risk of prolonged storage through the mechanism of increased hemolysis and free iron,” the authors wrote. However, the results of this systematic review and meta-analysis provided “no support for blood transfusion services implementing limits, or instituting preferential utilization, of red blood cell units that are fresh or stored for shorter periods,” they added.


Alexander PE, Barty R, Fei Y, et al. Transfusion of fresher versus older red blood cells in hospitalized patients: a systematic review and meta-analysis. Blood. 2015 December 1. [Epub ahead of print]