Review question
In people needing a blood transfusion, is it better to give blood that has been stored for a shorter time compared to a longer time?
Background
After donation, red blood cells (blood) can be stored for up to 42 days before being transfused to a person in need of a blood transfusion. It is not known whether blood stored for this long might be harmful, particularly in vulnerable patient groups, such as those needing intensive care.
Study characteristics
We investigated the consequences of giving transfusions of:
- blood stored for a shorter duration versus blood stored for a longer duration, and
- blood stored for a shorter duration versus blood stored for a standard length of time ('standard practice storage duration'; this period varies between hospitals)
to anyone needing a blood transfusion.
We searched the medical literature to 20 November 2017. We identified 22 studies, which included a range of 42,835 participants (newborn babies less than 4 weeks old (neonates), children, and adults). Eleven studies (2249 participants) compared transfusion of blood stored for a shorter duration versus transfusion of blood stored for a longer duration, and the other 11 studies (40,588 participants) compared transfusion of blood stored for a shorter duration versus transfusion of standard practice storage duration blood.
Quality of evidence
We assessed the quality of evidence for our results, which ranged from very low to moderate quality. These judgements are based on the number of trials and participants contributing data to each result, how similar the results were between trials, and the reliability of the trial methods used. Future research is highly likely to change the findings of results judged to be of very low quality, but is less likely to change the findings of other results, such as risk of death, for which we rated the evidence as moderate.
Key results
Transfusion of blood stored for a shorter duration versus blood stored for a longer duration
Eight studies focused on adults, two on children with severe anaemia (low blood count) and two on low birth weight neonates. In adults undergoing major surgery, transfusion of blood stored for a shorter duration versus blood stored for a longer duration probably leads to little or no difference in risk of death up to 30 days but the quality of evidence is moderate. In children we were uncertain whether transfusion of blood stored for a shorter duration increases or decreases risk of death, because the quality of the evidence is very low.
Transfusion of blood stored for a shorter duration versus standard practice storage duration blood
Eight studies focused on adults, most of whom were in hospital. Three studies enrolled critically ill neonates. Transfusion of blood of shorter storage duration versus blood of standard practice storage duration probably leads to little or no difference in risk of death in adults in the 30 days after transfusion. Whether transfusion of blood of shorter storage duration increases or decreases risk of death in critically ill neonates up to 30 days after transfusion is uncertain because the quality of evidence is very low.
Two studies in critically ill adults provided information on adverse reactions to transfusion, but had conflicting results. While one study found more transfusions associated with fever in the participants who received blood stored for a shorter duration than those who received standard practice storage duration blood, another study found no differences between the two groups.
Conclusion
We observed no clear difference in the risk of death at different time points between transfusion of blood stored for a shorter duration versus blood stored for a longer duration or versus blood stored for the standard practice storage duration.
The effect of storage duration on clinically important outcomes has now been investigated in large, high quality RCTs, predominantly in adults. There appears to be no evidence of an effect on mortality that is related to length of storage of transfused RBCs. However, the quality of evidence in neonates and children is low. The current practice in blood banks of using the oldest available RBCs can be continued safely. Additional RCTs are not required, but research using alternative study designs, should focus on particular subgroups (e.g. those requiring multiple RBC units) and on factors affecting RBC quality.
Red blood cell (RBC) transfusion is a common treatment for anaemia in many conditions. The safety and efficacy of transfusing RBC units that have been stored for different durations before a transfusion is a current concern. The duration of storage for a RBC unit can be up to 42 days. If evidence from randomised controlled trials (RCT) were to indicate that clinical outcomes are affected by storage duration, the implications for inventory management and clinical practice would be significant.
To assess the effects of using red blood cells (RBCs) stored for a shorter versus a longer duration, or versus RBCs stored for standard practice duration, in people requiring a RBC transfusion.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PubMed (for epublications), LILACS, Transfusion Evidence Library, Web of Science CPCI-S and four international clinical trial registries on 20 November 2017.
We included RCTs that compared transfusion of RBCs of shorter versus longer storage duration, or versus standard practice storage duration.
We used standard Cochrane methods.
We included 22 trials (42,835 participants) in this review.
The GRADE quality of evidence ranged from very low to moderate for our primary outcome of in-hospital and short-term mortality reported at different time points.
Transfusion of RBCs of shorter versus longer storage duration
Eleven trials (2249 participants) compared transfusion of RBCs of shorter versus longer storage duration. Two trials enrolled low birth weight neonates, two enrolled children with severe anaemia secondary to malaria or sickle cell disease, and eight enrolled adults across a range of clinical settings (intensive care, cardiac surgery, major elective surgery, hospitalised in-patients, haematology outpatients). We judged only two trials to be at low risk of bias across all domains; most trials had an unclear risk for multiple domains.
Transfusion of RBCs of shorter versus longer storage duration probably leads to little or no difference in mortality at seven-day follow-up (risk ratio (RR) 1.42, 95% confidence interval (CI) 0.66 to 3.06; 1 trial, 3098 participants; moderate quality evidence) or 30-day follow-up (RR 0.85, 95%CI 0.50 to 1.45; 2 trials, 1121 participants; moderate quality evidence) in adults undergoing major elective cardiac or non-cardiac surgery.
For neonates, no studies reported on the primary outcome of in-hospital or short-term mortality. At 40 weeks gestational age, the effect of RBCs of shorter versus longer storage duration on the risk of death was uncertain, as the quality of evidence is very low (RR 0.90, 95% CI 0.41 to 1.85; 1 trial, 52 participants).
The effect of RBCs of shorter versus longer storage duration on the risk of death in children with severe anaemia was also uncertain within 24 hours of transfusion (RR 1.50, 95% CI 0.43 to 5.25; 2 trials, 364 participants; very low quality evidence), or at 30-day follow-up (RR 1.40, 95% CI 0.45 to 4.31; 1 trial, 290 participants; low quality evidence).
Only one trial, in children with severe anaemia (290 participants), reported adverse transfusion reactions. Only one child in each arm experienced an adverse reaction within 24 hours of transfusion.
Transfusion of RBCs of shorter versus standard practice storage duration
Eleven trials (40,588 participants) compared transfusion of RBCs of shorter versus standard practice storage duration. Three trials enrolled critically ill term neonates; two of these enrolled very low birth weight neonates. There were no trials in children. Eight trials enrolled critically ill and non-critically ill adults, with most being hospitalised. We judged four trials to be at low risk of bias across all domains with the others having an unclear risk of bias across multiple domains.
Transfusion of RBCs of shorter versus standard practice storage duration probably leads to little or no difference in adult in-hospital mortality (RR 1.05, 95% CI 0.97 to 1.14; 4 trials, 25,704 participants; moderate quality evidence), ICU mortality (RR 1.06, 95% CI 0.98 to 1.15; 3 trials, 13,066 participants; moderate quality evidence), or 30-day mortality (RR 1.04, 95% CI 0.96 to 1.13; 4 trials, 7510 participants;moderate quality evidence).
Two of the three trials that enrolled neonates reported that there were no adverse transfusion reactions. One trial reported an isolated case of cytomegalovirus infection in participants assigned to the standard practice storage duration group. Two trials in critically ill adults reported data on transfusion reactions: one observed no difference in acute transfusion reactions between arms (RR 0.67, 95% CI 0.19 to 2.36, 2413 participants), but the other observed more febrile nonhaemolytic reactions in the shorter storage duration arm (RR 1.48, 95% CI 1.13 to 1.95, 4919 participants).
Trial sequential analysis showed that we may now have sufficient evidence to reject a 5% relative risk increase or decrease of death within 30 days when transfusing RBCs of shorter versus longer storage duration across all patient groups.