Red blood cells' shelf life might depend on donor's genes


Red blood cells are the most commonly used blood product, with more than 11 million units transfused annually in the United States alone, according to the Centers for Disease Control and Prevention. While they are a lifesaving powerhouse, it is possible that ongoing research can improve the quality of this product. Early findings from a large, multicenter study suggest that the shelf life of red blood cells might also be dependent on the donor’s genes. There appears to be variation from person to person in how well one’s red blood cells can resist biological insults such as oxidative or osmotic stress or storage in the refrigerator.

The January issue of Transfusion reports research findings in seven articles and an editorial about the development, execution and preliminary results from the Red Blood Cell Omics (RBC-Omics) Study, one of the largest projects of the Recipient Epidemiology and Donor Study-III (REDS-III) research program funded by the National Heart Lung and Blood Institute (NHLBI).

“We want to ensure that patients will receive maximum benefit from their red blood cell transfusions,” said Michael Busch, M.D., of Vitalant Research Institute and the study’s principal investigator. “It is important to eventually identify and reduce the number of red blood cells in the bag that are more likely to break down once transfused. That is one of the major reasons why we launched the RBC-Omics study.”

Iron-containing hemoglobin in red blood cells carries oxygen throughout the body. Transfusions increase the supply of oxygen to organs in patients with anemia or a chronic blood condition. Red blood cell units can be stored in the refrigerator (at 4oC) for up to 42 days. During storage, some of these cells can be damaged, breaking down more easily and releasing cell-free hemoglobin either in the storage bag, or once transfused.

“Cell-free hemoglobin, what we call hemolysis, should be minimized whenever possible,” says Simone Glynn M.D. M.Sc. MPH, chief of the Blood Epidemiology and Clinical Therapeutics branch of the NHLBI. “If the red blood cells are not working well when transfused, the patient’s body will further break them down; potentially releasing excess iron, which can lead to inflammation and infection.”

Current guidelines regulating blood donation amount and frequency, as well as storage of blood components are the same for all donors. “Some donors will eventually become deferred from donation for a low hemoglobin level. However, other blood donors can give very frequently without experiencing anemia. We do not understand why; but it might be due to genetic traits that affect absorption of iron and levels of hemoglobin,” said Glynn.

The researchers with the Red Blood Cell Omics had a hypothesis. They believe that common and rare genetic variations, which have evolved in response to a myriad of environmental exposures including malaria and other infectious diseases, might play a significant role in how red blood cells respond to storage, conserve their key functions and properties and are susceptible to damage.

To uncover some of these factors, the RBC-Omics Study enrolled 13,403 donors through four U.S. blood centers, with a focus on racial-ethnic minority donors and frequent blood donors. The study also performed the largest genome-wide association study (GWAS) study of healthy human blood donors to date; which led to the identification of genetic variations associated with red blood cells’ response to stressors.

These findings might open the door to a future in which donor genotype is taken into account to determine the time limits of blood storage and helps predict recovery and survival of cells after storage. The researchers also anticipate that the genetic variations they identify, along with other associations like age and gender, may help predict risk of transfusion-associated complications in diseases like sickle cell anemia.

More about the RBC-Omics Study

The RBC-Omics Study is also a resource for the future, with numerous analyses being conducted to understand the genetic, metabolomic and other factors which influence red blood cell hemolysis, blood iron in donors and outcomes in recipients of transfusions from enrolled donors (e.g., increments in hemoglobin levels following transfusions). The study is also identifying genetic and behavioral factors that influence development of iron-related disorders such as restless leg syndrome and Pica in blood donors.

The REDS-III study has been running since 2011 with numerous studies investigating different aspects of blood donation and transfusion safety and efficacy. More information on the REDS-III program and studies and detailed links to the new RBC-Omics publications can be found at the REDS-III program site, and the recent article in the virtual issue of Transfusion.