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Age of transfused cells does not affect mortality rate
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Critically ill adults who received allogeneic red cells stored for a longer duration had comparable 90-day mortality rates as adults who received the freshest cells, according to results of an international, multicenter, randomized double-blind trial published in The New England Journal of Medicine.
Usual practice is for blood banks to use the oldest compatible red-cell units available for transfusions, despite that red cells undergo structural, biochemical and metabolic changes during storage. Critically ill patients may be more sensitive to these changes, and transfusion of older cells has been associated with increased morbidity and mortality among critically ill, surgical and trauma patients.
However, both the ABLE and INFORM trials showed no significant differences between patients who received fresher or older red cells.
Due to potential limitations of these trials, D. James Cooper, MD, professor of intensive care medicine and director of the Australian and New Zealand Intensive Care Research Centre at Monash University in Melbourne, Australia, and colleagues conducted the TRANFUSE trial to compare the effect of using the freshest and oldest available red cells in 4,919 high-risk critically ill patients.
Researchers randomly assigned 2,457 patients to the short-term storage group and 2,462 patients to the long-term storage group. Baseline characteristics appeared comparable between the groups, except that patients in the short-term storage group were older (62.5 ± 16.8 years vs. 61.4 ± 17.3 years; P = .02.
Mean storage duration of cells was 11.8 days in the short-term storage group and 22.4 days in the long-term storage group.
Ninety-day all-cause mortality served as the primary outcome.
Results — published to coincide with the European Society of Intensive Care Medicine Annual Congress in Vienna — showed there were 610 deaths (24.8%) in the short-term group and 594 deaths (24.1%) in the long-term group, for an absolute risk difference of 0.7 percentage points (95% CI, –1.7 to 3.1), which did not reach statistical significance.
At 180 days, the absolute risk difference dropped to 0.4 percentage points (95% CI, –2.1 to 3).
Researchers reported no statistically significant differences in 28-day mortality, rates of persistent organ dysfunction or death at 28 days, new bloodstream infections, mechanical ventilation, renal-replacement therapy or ICU length of stay.
More patients in the short-term group experienced febrile nonhemolytic transfusion reactions (5% vs. 3.6%; absolute risk difference, 1.4 percentage points; 95% CI, 0.3-2.6; OR = 1.42; 95% CI, 1.07-1.88), but the difference lost significance after adjustment.
“Our trial provides strong evidence that transfusion of the freshest available red cells as compared with standard-issue (oldest available) red cells provides no clinically meaningful benefits in critically ill patients,” Cooper and colleagues wrote. “Our results support the current international usual practice of transfusing patients with the oldest red cells available.” – by Alexandra Todak
Disclosures: Cooper reports grant or nonfinancial support from the National Health and Medical Research Council, Australia; the Health Research Council, New Zealand; the Health Research Board, Ireland; Australian Red Cross Blood Service during the conduct of the study; and the National Blood Authority, Australia. He also reports personal fees from Eustralis Pharmaceuticals, and a principal investigator role on the INFORM CIHR grant, but not a site investigator role for INFORM. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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Cooper and colleagues concluded that older, standard-issue red blood cells are safe, and that there is no benefit to transfuse fresher red blood cell units to critically ill adults. However, there are a number of issues with these analyses.
To lump together severely injured trauma patients who receive massive transfusions (eg, more than six red blood cell units in the first 12 hours) with patients who received standard transfusions for anemia dilutes any possible differences related to the concentrations of pro-inflammatory or other mediators that are the results of the storage lesion.
Secondly, although this patient population was made up of critically ill adults, it was a heterogenous population that, in many ways, should not be compared. The investigators in the ABLE trial recognized this and determined there is a difference in patients who received more than six units of red blood cells, similar to previous data on massively transfused trauma patients.
One must be careful in limiting the conclusions of such studies because the patient groups that are most affected by older or fresher red blood cells may not be properly represented and subsequently ignored when studying heterogenous populations, even if they are all critically ill. Secondary analyses should be completed that control for the numbers of units transfused, mechanism and types of injuries, etc, to elucidate the effects of red blood cell storage on the most vulnerable populations.
References:
Cooper DJ, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1707572.
Mack JP, et al. Abstract #96. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Zallen G, et al. Am J Surg. 1999;178:570-572.
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