This article first appeared in the St. Louis Beacon, Sept. 24, 2013: Dr. Philip Spinella served 12 years in the United States military, including a year treating traumatic injuries in the 31st Combat Support Hospital in Baghdad. During his deployment, he was also part of a small group of physicians evaluating transfusion practices in treating hemorrhagic shock resulting from battlefield injuries.
Spinella co-authored multiple studies with others from his group indicating that transfusion of red blood cells stored for a prolonged period may be associated with an increase in complications and mortality. Now he's looking at the same issue as it relates to critically ill children.
One report based on the Iraq study concluded that fresh whole blood was preferable to the stored blood components (red cells, platelets and plasma) that had been shipped from the United States. These cells had been stored for longer than 21 days, with a median storage time of 33 days.
The report concluded that while the risk of viral infection from fresh blood was very slightly higher even after prescreening, fresh whole blood was superior to aged cells for improved physiological effects such as cardiac output and better clinical outcomes.
Spinella, associate professor of pediatrics at Washington University Medical School, and director of the pediatric Blood Research Program, continues to question how well red blood cells maintain their safety and functionality after relatively long storage. He is specifically interested in the question as it relates to growing children who are critically ill.
Age of banked blood and critically ill children
Spinella has received a $7.8 million grant from the National Institutes of Health to study whether the age of transfused red blood cells in critically ill children affects the risk of new or progressive multiple organ failure. His co-investigator is Dr. Marisa Tucci of Sainte-Justine Hospital in Montreal.
Children in the United States requiring transfusions are given the oldest available blood, the standard blood banking practice. Storage time averages 17-21 days, and ranges from 2 to 42 days for children. Certain patients, at St. Louis Children’s hospital and many other medical centers, are always given fresh blood products — babies less than six months old, children having cardiac surgery, and certain children with sickle cell anemia.
In Spinella's five-year study, 1538 critically ill children, from 3 days to 16 years of age, will be divided randomly into two groups. One group will receive fresh red blood cells, stored less than one week. The other group will be treated with the standard transfusion protocol. Those who would already receive fresh red blood cell transfusions will not be included in the study, nor will patients whose parents have not given permission for participation.
About thirty medical centers in the U.S. and Canada will participate in the study. The Canadian Institutes of Health Research is funding Canada-based costs.
Only blood bank personnel will know which patients have received fresh vs. standard red blood cells. The label indicating length of storage will be obscured in the blood bank; such an experiment in which neither patient nor doctor knows the which kind of blood is given is called “double-blind.”
Clinical efficacy of older red blood cells
When the Food and Drug Administration changed its standards for new drug approval to include tests of both safety and efficacy, blood products were “grandfathered.” New formulations for red blood cell storage solutions doubled the time that cells could be stored and transfused safely according to those decades-old standards. However, blood processors were not required to show that these older cells could take up and release oxygen as well as fresh cells when transfused.
“It’s like thinking you have a good car because the body is intact. But if the engine does not work, the car is not very functional. The red cells circulate intact, but we have no idea if, when they’re stored for 42 days or close to that, they actually deliver oxygen the way we think they should” Spinella said.
Laboratory studies have repeatedly shown that red blood cells change during storage. For instance, by 14 days, they lose flexibility. Oxygen exchange occurs in capillaries, rather than in veins and arteries. As the cells move through the narrow capillaries, they undergo changes of shape and don't regain flexibility for a day or so.
Other changes with storage, having to do with energy metabolism, clotting, and immune function, have been well documented in the laboratory.
Results will be important to blood banks
Increased storage times are important in blood banking for maintaining inventory. As a general practice, the Red Cross sends red cells on request to hospital blood banks. If the cells are not used by 35 days, as may happen in rural areas, they are redistributed to large urban medical centers, including St. Louis Children’s Hospital. In these large centers, demand is great, and the blood is less likely to be wasted.
There is a difference of opinion in the transfusion literature on whether length of blood storage correlates with clinical adverse results. This study is significant because it is the first large double-blind investigation on children in pediatric intensive care units.
“This is the first study of its kind in this particular population, who typically require a lot of transfusions, and are at higher risk of transfusion-related complications. If long storage times do have a negative effect on patient outcomes, it could seriously affect our ability to preserve our supply of blood," Dr. Ronald Jackups, who will be in charge of the blood banking at Children’s Hospital during the study, said.
"Think of it like a grocery store stocking milk. If all the expiration dates on milk were cut in half, because it was shown that milk stored that long was unsafe, stores would have to stock less milk at any point in time in order to avoid wasting it, which subsequently could lead to shortages. We should only shorten expiration dates on blood if there’s proof that older products are truly more dangerous. We need large studies like these one to answer that question once and for all “
Spinella points out that large studies would also be appropriate to show efficacy if new formulas for red cell storage should be adopted.
The American Red Cross supplies blood to Children’s Hospital bank.
“The Red Cross welcomes this study and should evidence indicate a need for change in current practices, the Red Cross will use the best available science to provide the safest possible blood for patients,” Dan Fox, local communications program manager, said.