“Age,” the great boxer Muhammad Ali famously said, “is whatever you think it is. You are as old as you think you are.”
The role that aging plays in vitality, strength, and wisdom has long been debated, but more recently the question of whether younger is better has been raised about red blood cells. Currently, blood bank regulations allow for storage of red cells for up to 6 weeks before transfusion. Some observational studies, including data published in the Journal, suggest this might be too long, finding an association between red cell units stored for more than 2 to 3 weeks and serious adverse events.
Given the confounding inherent in observational data, Steiner and colleagues designed a randomized controlled trial to more definitively explore this question. Their findings, now published in the Journal, call the conclusions of these prior observational studies into question.
Investigators enrolled participants 12 years of age or older who were undergoing complex cardiac surgery and were deemed likely to undergo red blood cell transfusions. For all intraoperative and postoperative transfusions, participants were randomized to either a shorter storage group (RBCs stored for 10 days or less) or a longer storage group (RBCs stored for 21 days or more). The primary outcome was the change in the Multiple Organ Dysfunction Score (MODS), a measure from 0-24 that is sensitive to minor changes in clinical status and incorporates mortality, through day 7, death or discharge.
Fourteen hundred and eighty-one participants underwent randomization, with 1098 who ultimately received red cell transfusions included in the analysis. Participants had a median age in their early 70s, were about 40% male, and 90% white; there was no significant difference in baseline MODS between groups. The median storage time of RBCs was 7 days in the short storage group and 28 days in the longer storage group.
The results: there was no significant difference in the primary endpoint, with a mean change in MODS of 8.5 in the shorter storage group versus 8.7 in the longer storage group (p = 0.44). There were no differences in either serious or non-serious adverse events except that hyperbilirubinemia was more common in the longer storage group, likely attributable to hemolysis in older red blood cells. While statistically significant, the absolute change in total serum bilirubin was 1.5mg/dL in the longer storage group versus 0.8 in the shorter-term storage group — a difference that seems unlikely to be highly clinically significant.
NEJM Deputy Editor Dr. Dan Longo describes this trial as “an important study that demonstrates no clinical benefit to the preferential transfusion of younger red blood cells.” He cautions, however, against overstating this conclusion: given that the older blood group used red cells stored for a median of 4 weeks and current regulations allow storage up to 6, he notes, “This trial doesn’t address whether 5- or 6-week-old blood might be more harmful.”
With that caveat in mind, age as studied here doesn’t seem to make a difference. When we here at the Now@NEJM blog called Mr. Ali for comment about the fact that he had been right all along, he didn’t seem surprised: “It’s hard being humble,” he says, “when you’re as great as I am.”
See also: NEJM Quick Take video summary on this trial