Image of the cover of the January edition of the Transfusion journal
Credit: Transfusion journal

A donor’s genes might hold the key to the shelf life of red blood cells

Every two seconds someone in the United States needs blood.

Five million people receive a blood transfusion every year in the U.S. In a country where blood is perennially in short supply, it is the most common medical procedure of all. Yet giving to a blood bank is not always a slam dunk—some people get turned away because of strict rules meant for the safety of donors and recipients alike.

Of blood’s three components – red cells, plasma and platelets – red blood cells are the most commonly used blood product in the world, with 10.5 million units transfused annually in the U.S. alone.

No wonder scientists think so much about this lifesaving powerhouse—who it came from, what’s in it, how it’s stored. There’s one big problem, though: red blood cells can deteriorate easily and become useless, even dangerous if transfused.

Storage time and temperature have long been considered key factors in the shelf life of these cells. Now, early findings from a large, multicenter study suggest that the donors’ genes may also play an essential role.


Image of the cover of the January edition of the Transfusion journal

“There seems 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,” said Michael Busch, M.D., Ph.D., director of the Vitalant Research Institute and also the study’s Principal Investigator.

The January issue of the journal Transfusion reported these findings in a compilation of 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, which is funded by the National Heart Lung and Blood Institute (NHLBI).

“We want to ensure that patients receive maximum benefit from their red blood cell transfusions,” said Busch. Identifying and reducing the number of red blood cells that are likely to break down once transfused is extremely important, he added. And for good reason: bad cells can do big damage. They can cause infection and inflammation and slow down, or even prevent, a patient’s recovery.

But when they are healthy, the transfusions they make possible can be miracle workers for patients with anemia, whether it’s acute and due to traumatic blood loss, or long term and due to treatments, such as chemotherapy, or a chronic blood condition such as sickle cell disease.

Iron-containing hemoglobin in the cells carries oxygen throughout the body, and transfusions increase that supply of oxygen to the patients’ organs. The challenge is figuring out the most viable cells to deliver during transfusions. “That is one of the major reasons we launched the RBC-Omics study,” Busch said.

Red blood cell units can be refrigerated 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., MPH, chief of the Blood Epidemiology and Clinical Therapeutics branch of the NHLBI and the scientific project officer for the REDS-III. 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.

Guidelines regulating how much and how often donors can give blood – one pint every eight weeks – as well as how their blood should be stored, apply equally to everybody

“Some donors will eventually be turned away due to a low hemoglobin level, said Glynn. “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.”

The researchers with the Red Blood Cell Omics had their own hypothesis: 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 vulnerable to damage.

To uncover some of these factors, the RBC-Omics Study enrolled 13,403 donors at four U.S. blood centers, paying special attention to the recruitment of racial-ethnic minority donors and frequent blood donors. The study also performed the largest genome-wide association 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, said Busch, might open the door to a future in which donor genotype is taken into account to determine time limits for blood storage and predict recovery and survival of cells after storage.

The RBC-Omics Study is also a resource for the future. Researchers are mining the data to understand the genetic, metabolomic and other factors influencing red blood cell hemolysis, blood iron in donors, and the outcomes of transfusion recipients. 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.

Since 2011, the NHLBI REDS-III research program has conducted numerous studies aimed at improving blood transfusion benefits and reducing associated risks.