The oldest blood available for transfusions releases large and potentially harmful amounts of iron into patients’ bloodstreams, a Columbia University study has found. Based on the findings, the researchers recommend that the US Food and drug Administration reduces the maximum storage limit of red blood cells from six weeks to five weeks, as long as sufficient blood supplies are available.
“Our recommendation will be controversial, but we think we have real data to support it,” said the study’s co-leader Dr Steven Spitalnik, professor of pathology & cell biology at Columbia and medical director of the clinical laboratories at NewYork-Presbyterian/Columbia. “Recent studies have concluded that transfusing old blood has no impact on patient outcomes, but those studies didn’t exclusively examine the oldest blood available for transfusions. Our new study found a real problem when transfusing blood that’s older than five weeks.”
Transfusion of red blood cells is the most common procedure performed in hospitalised patients, with approximately 5m patients receiving red blood cell transfusions annually in the US. “But the longer you store blood, the more the cells become damaged,” said the study’s co-leader Dr Eldad Hod, associate professor of pathology & cell biology at Columbia and clinical pathologist at NewYork-Presbyterian/Columbia. Currently, the US Food and Drug Administration allows units of red blood cells to be stored for up to six weeks before they must be discarded.
In the study, the researchers randomly assigned a group of 60 healthy volunteers to receive a unit of red blood cells that had been stored for one, two, three, four, five, or six weeks. The volunteers were then monitored for 20 hours after transfusion.
Within hours after transfusion, seven of the nine volunteers who received the 6-week-old blood could not appropriately metabolise the damaged cells, thereby releasing large amounts of iron into their bloodstream. Only one volunteer who received younger blood had a similar response, with blood that had been stored for five weeks.
None of the volunteers were harmed by the transfusion, but previous studies have shown that excess iron can enhance blood clots and promote infections. “Based on the amount of iron circulating in the blood of the volunteers who received 6-week-old blood, we’d predict that certain existing infections could be exacerbated,” said Hod. “Thus, for ill, hospitalised patients, this excess iron could lead to serious complications,” said Spitalnik.
The true impact of 6-week-old blood on the rate of complications in patients is likely to be small, the researchers said, but since millions of Americans receive transfusions each year, even a 1% difference in complications could affect a large number of patients.
“It’s estimated that up to 10% to 20% of blood units used for transfusions have been stored for more than five weeks, so the number of patients who are likely to receive a unit of very old blood is substantial,” Hod added.
“Based on our findings of potential harm, we think the prudent thing to do at this time is for the FDA to reduce the maximum storage period,” said Spitalnik. “The Netherlands, UK, Ireland, and the National Institutes of Health have limited storage to 35 days, and we think that can be achieved throughout the US without seriously affecting the blood supply.”
Abstract
Background: Some countries have limited the maximum allowable storage duration for red cells to 5 weeks before transfusion. In the US, red blood cells can be stored for up to 6 weeks, but randomized trials have not assessed the effects of this final week of storage on clinical outcomes.
Methods: Sixty healthy adult volunteers were randomized to a single standard, autologous, leukoreduced, packed red cell transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage (n = 10 per group). 51-Chromium posttransfusion red cell recovery studies were performed and laboratory parameters measured before and at defined times after transfusion.
Results: Extravascular hemolysis after transfusion progressively increased with increasing storage time (P < 0.001 for linear trend in the AUC of serum indirect bilirubin and iron levels). Longer storage duration was associated with decreasing posttransfusion red cell recovery (P = 0.002), decreasing elevations in hematocrit (P = 0.02), and increasing serum ferritin (P < 0.0001). After 6 weeks of refrigerated storage, transfusion was followed by increases in AUC for serum iron (P < 0.01), transferrin saturation (P < 0.001), and nontransferrin-bound iron (P < 0.001) as compared with transfusion after 1 to 5 weeks of storage.
Conclusions: After 6 weeks of refrigerated storage, transfusion of autologous red cells to healthy human volunteers increased extravascular hemolysis, saturated serum transferrin, and produced circulating nontransferrin-bound iron. These outcomes, associated with increased risks of harm, provide evidence that the maximal allowable red cell storage duration should be reduced to the minimum sustainable by the blood supply, with 35 days as an attainable goal.
Authors
Francesca Rapido, Gary M. Brittenham, Sheila Bandyopadhyay, Francesca La Carpia, Camilla L’Acqua, Donald J McMahon, Abdelhadi Rebbaa, Boguslaw S Wojczyk, Jane Netterwald, Hangli Wang, Joseph Schwartz, Andrew Eisenberger, Mark Soffing, Randy Yeh, Chaitanya Divgi, Yelena Z Ginzburg, Beth H Shaz, Sujit Sheth, Richard O Francis, Steven L Spitalnik, Eldad A Hod
[link url="http://newsroom.cumc.columbia.edu/blog/2017/01/10/transfusions-of-old-blood-may-harm-some-patients/"]Columbia University material[/link]
[link url="https://www.jci.org/articles/view/90837"]Journal of Clinical Investigation abstract[/link]