Good Transfusion Outcomes After Prolonged Blood Storage

Roxanne Nelson, BSN, RN

December 16, 2015

ORLANDO — Prolonged storage of red blood cells (RBCs) does not appear to affect their ability to deliver oxygen, and older products (stored for 25 to 35 days) are as effective as those stored for shorter periods of time (up to 10 days), according to a randomized trial conducted in Uganda.

The results were presented here at the annual American Society of Hematology 57th Annual Meeting and were published in the December 15 issue of JAMA.

No other trial examining this topic has compared such wide variation in storage duration, write Philip C. Spinella, MD, from the Washington University School of Medicine in St. Louis, Missouri, and Jason Acker, MBA, PhD, from the University of Alberta in Edmonton, Canada, in an accompanying editorial.

"Accordingly, this trial makes an important contribution to the literature, by indicating that RBCs near the end of expiration may be efficacious at increasing oxygen delivery and reversing oxygen debt," they explain.

However, better data collection in this field is needed, they add.

Does Storage Lead to Deterioration?

Stored RBCs deliver oxygen to patients with critical oxygen need, as demonstrated by the restoration of aerobic tissue metabolism and clearance of lactate, said study author Christine M. Cserti-Gazdewich, MD, FRCPC, assistant professor of medicine and transfusion medicine specialist at the University of Toronto, who presented the findings.

"We found no justification to shorten the current storage duration for RBCs as judged by their fundamental role to deliver oxygen," she said.

Current regulations allow RBCs to be stored in approved solutions for about 5 to 6 weeks. In the past, cell survival studies and in vitro markers of hemolysis were used to establish the maximal duration of blood storage rather than measures of oxygen delivery.

During storage, RBCs undergo cumulative structural, biochemical, and enzymatic changes that can collectively impair the ability of erythrocytes to deliver oxygen to tissues and contribute to adverse patient outcomes, the authors point out.

Changes in RBCs during storage have led to concerns about whether the allowable storage limit should be shortened, Dr Cserti-Gazdewich noted.

Support From Previous Research

Three previous randomized trials have examined the frequency of adverse events after the transfusion of RBC units stored for different periods of time.

In the Age of Red Cells in Premature Infants (ARIPI) study (JAMA. 2012;308:1443-1451), there was no significant difference in the frequency of five major adverse outcomes in premature low-birth-weight infants. In the Age of Blood Evaluation (ABLE) trial (N Engl J Med. 2015;372:1410-1418), the length of blood storage had no significant effect on 90-day mortality in critical care patients. And in the Red Cell Storage Duration Study (RECESS), blood storage duration had no significant effect on organ dysfunction score after cardiac surgery, as reported by Medscape Medical News.

However, none of these studies was specifically designed to examine the effect of blood storage duration on oxygen delivery to tissues. They were conducted in patients receiving RBCs that were not necessarily needed, not dose-standardized, not assessed for RBC performance, and not always free of overlap/storage-time similarity, Dr Cserti-Gazdewich pointed out.

"In addition, these RCTs were conducted in high-income countries and in high-technology care settings, with 'blood inventory wealth,' and findings may not be generalizable to the other half of the world," she said.

Because RBC availability is directly related to permitted shelf-time, reduced availability would have the worst impact in developing nations, she added.

No Differences Across Time Points

Dr Cserti-Gazdewich and her colleagues evaluated 290 Ugandan children (age range, 6 to 60 months) who presented to a university hospital urgent care facility with hemoglobin levels at or below 5 g/dL and associated lactate levels of at least 5 mmol/L.

All patients had lactic acidosis caused by severe anemia, but did not have shock, trauma, impaired cardiac function, refractory hypoxia, liver disease, or tissue injury.

Half the children were randomized to leukoreduced RBCs that were stored for 1 to 10 days and half were randomized to leukoreduced RBCs that were stored for 25 to 35 days. All received 10 mL/kg of RBCs during hours 0 to 2, and, if indicated, they then received an additional 10 mL/kg during hours 4 to 6.

The primary end point was a lactate level of 3 mmol/L or below at 8 hours, using a margin of noninferiority equal to an absolute difference of 25%.

Secondary end points included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health 30 days after transfusion.

At presentation, patients had a mean hemoglobin level of 3.7 g/dL and a mean lactate level of 9.3 mmol/L. Blood lactate levels were measured at every 2 hours after transfusion.

The median duration of RBC unit storage was 8 days (range, 7 - 9 days) for shorter storage and was 32 days (range, 30 - 34 days) for longer storage.

The proportion of patients meeting the target mean lactate level of 3 mmol/L or below was 0.58 (95% confidence interval [CI], 0.49 - 0.66) in the shorter-storage group and 0.61 (95% CI, 0.52 - 0.69) in the longer-storage group.

Mean lactate levels were not significantly different between the two groups at any time point up to 24 hours after transfusion. For secondary outcomes, measurements did not differ significantly between the two groups. And clinical and laboratory changes in cerebral tissue oxygen saturation and electrolyte abnormalities improved to the same degree in both groups after transfusion.

Adverse events, overall survival, and 30-day recovery did not significantly differ between the two groups. Eight patients died (three in the longer-storage group and five in the shorter-storage group) during the 24-hour period from the start of transfusion. Four other patients (two in the longer-storage group and two in the shorter-storage group) died in the hospital after the initial 24-hour observation period.

Better Data Collection Needed

In their editorial, Drs Spinella and Acker point out that given that previous trials have demonstrated that fresh RBCs do not improve outcomes, "perhaps the focus should shift from duration of storage to other factors affecting RBC quality. One such factor may be donor characteristics, such as sex, age, frequency of donation, and ABO and Rh type."

They also point to the need for better data collection, which could facilitate more comprehensive research in this area of study. Currently, the majority of healthcare systems do not collect and analyze data that would allow for improvement in transfusion-related outcomes.

"More complete data throughout the continuum from donation to transfusion are needed to improve outcomes for patients requiring transfusions," they say. "Hospitals should collect data on patients receiving transfusions, the indications for transfusion, the timing and dose of each blood product transfused, and the physiologic response to transfusion."

"Only with better data can future studies determine which therapies or strategies are optimal to improve outcomes for patients requiring transfusions," the editorialists conclude.

The study was fully funded by the National Institutes of Health. Dr Cserti-Gazdewich has disclosed no relevant financial relationships. Study coauthor Christopher Stowell, MD, PhD, from the Massachusetts General Hospital in Boston, reports serving on the scientific review committee for Haemonetics Corporation. Dr Spinella reports receiving personal fees from New Health Sciences and Terumo BCT, and having a pending patent for Blood Substitute Composition and Method of Use. Dr Acker reports serving on advisory boards for Biomet Biologics and BioLife Solutions, and receiving personal fees from Aquila Diagnostic Systems.

JAMA. 2015;314:2509-2510, 2514-2523. Editorial, Abstract

American Society of Hematology (ASH) 57th Annual Meeting: Abstract 769. Presented December 7, 2015.

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