ORLANDO – Stored red blood cells continue to do their primary job of tissue reoxygenation for more than a month after being collected, a finding that has profound positive implications for countries where blood products are in perennially short supply and demand is high, said investigators from Africa and North America.
In a randomized controlled clinical trial, red blood cells (RBCs) stored for 25 to 35 days were not-inferior to RBCs stored for 1 to 10 days for tissue reox-ygenation in African children with severe anemia with lactic acidosis.
“We found no justification to shorten the current storage duration for RBCs judged by their fundamental role to deliver oxygen,” said Dr. Christine M. Cserti-Gazdewich from the University of Toronto, Ontario, Canada.
Their findings suggest that stored RBCs should be evaluated by their ability to effectively deliver oxygen to tissues rather than by the cell survival measures and in vitro markers of hemolysis used as the current standard for viability by regulatory agencies, Dr. Cserti-Gazdewich said at the American Society of Hematology annual meeting.
The study clinicaltrials.gov ID NCT01586923 is also published online in JAMA.
“This study won’t change our clinical practice, but it will substantiate what we have been doing,” said co-author Dr. Walter H “Sunny” Dzik from Mas-sachusetts General Hospital in Boston, in an interview.
“We didn’t go into this business to harm people, yet there’s a lot of lab data that has been pointing fingers at us, suggesting rather forcefully that by try-ing to manage blood inventories using older blood that we’re harming people,” he said.
Concerns about the shelf life of RBCs derive from evidence that the cells undergo cumulative changes in structure, biochemistry, and enzymatic active that ultimately could degrade their ability to deliver oxygen to target tissues. But those studies were based largely on laboratory findings and not on clinical practice, she noted.
To see whether RBCs stored for up to 5 weeks could be as effective at tissue oxygenation as more recently packaged cells, the investigators conducted a randomized clinical trial at a university hospital urgent-care facility in Kampala, Uganda, where diseases such as malaria and sickle-cell anemia, as well as malnutrion, cause severe anemia on a scale seldom seen in the developed world.
They enrolled 290 children from the ages of 6 to 60 months who presented with lactic acidosis due to severe anemia in the absence of shock, trauma, impaired cardiac function, refractory hypoxia, liver disease, or tissue injury. The patients all had hemoglobin levels of 5 g/dL or5 less, and serum lactate levels of 5 mM or greater.
The patients were randomly assigned, 145 to each study arm, to receive leukoreduced RBCs stored for either 1-10 days or from 25 to 35 days. All patients received 10 mL/kg of RBCs over 2 hours at the start of the study and, if indicated per protocol, an additional 10 mL/kg during hours 4-6. Blood lactate levels were measured at baseline and at 2, 4, 6, 8 and 24 hours.
The mean hemoglobin level at presentation was 3.7 ±1.3 g/dL and mean lactate was 9.3 ±3.4 mM.
The investigators found that the proportion of patients achieving a lactate ≤ 3 mM at 8 hours was 58% among patients who received the short-storage RBCs, compared with 61% among patients who received long-storage cells (P = 0.72). This result met the primary endpoint of non-inferiority for long-er-stored RBCs.
In fact, there were no significant differences between the groups in mean lactate levels at any of the time points beyond baseline.
There were no significant differences in lactate clearance, and there were similar degrees of improvement in clinical assessments, serial measurements of hemoglobin concentration, cerebral tissue oxygen saturation, and electrolyte abnormalities following RBC transfusions.
Adverse events, 30-day recovery, and survival were also comparable between the groups.
The authors also found in a pre-specified sub-group analysis that there were no significant between group differences in those patients who received a total of 20 mL/kg RBCs, Dr. Cserti-Gazdewich said.
“This is a crushingly urgent problem, in that there have been belief systems developed over the last couple of years that older blood is not as good as newer blood, without any real evidence to support that. The evidence that Christine is [presenting], I think, is pretty compelling evidence that that hy-pothesis is incorrect,” commented Dr. Mark Crowther, Professor and Chair in the Department of Pathology and Molecular Medicine of McMaster Univer-sity in Hamilton, Ontario, Canada. Dr. Crowther moderated a briefing where Dr. Cserti-Gazdewich presented the data.
The study was funded by the National Institutes of Health. Dr. Cserti-Gazdewich, Dr. Dzik, and Dr. Crowther reported having no relevant conflicts of interest.