The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, is funding nine research grants to determine if the safety and efficacy of red blood cell transfusions vary depending on how long the cells have been stored. One of the grants supports the first large, multi-center, randomized clinical trial to compare outcomes in heart surgery patients who receive transfusions of red blood cells that have been stored for shorter or longer amounts of time. The other eight research grants provide about $3.9 million per year over four years to assess the safety and efficacy of red blood cell transfusions.
"These are the first research projects to systematically examine the storage- and preparation-dependent changes that red blood cell units undergo, said NHLBI Acting Director Susan B. Shurin, M.D. "These basic and translational studies embody the NHLBI's goal to advance the science of blood safety in the nation. What we learn will help guide clinical practice."
U.S. medical workers administer about 14.7 million bags of blood to about five million patients each year. These transfusions contain red blood cells to treat patients with anemia or to replenish blood lost to surgery or severe injury.
While transfusions unquestionably save the lives of many patients, they can cause complications. Some studies suggest that the way donated blood is processed and the amount of time it is stored play a role in the changes that occur.
Currently, FDA regulations allow facilities to store red blood cells for up to 42 days at about 4 degrees Celsius (39 degrees Fahrenheit) before being transfused. The average age of transfused red blood cells in the United States is estimated to be a little more than 16 days.
Studies have shown that blood processing and storage cause several changes in red blood cell units, including lower concentrations of molecules that regulate how oxygen is delivered to patients' tissues. Storage and preparation also affect the deformability of red blood cells. Deformability normally allows the cells to squeeze through capillaries half their size.
Scientists do not fully understand the causes, extent, and timing of these changes, or if they affect transfused patients' health. Recent research on patient outcomes has yielded conflicting results. For example, some studies suggest that red blood cells stored for longer periods of time are less effective and more likely to harm transfusion recipients. They associate older stored red cells with more complications and deaths among heart surgery patients, trauma patients, and critically ill patients in the intensive care unit. In contrast, other investigations have found no differences in clinical outcomes using red cells stored short-term or long-term.
Most of these studies, however, were observational and cannot prove cause and effect. In addition, these studies might be difficult to interpret accurately because they cannot be adjusted to rule out potential confounding effects such as patients' illnesses, because they involved small sample sizes, or because other factors prevent the results from being applied to broader groups.
RECESS: A Clinical Trial for Blood Storage Time
The NHLBI's Red Cell Storage Duration Study, or RECESS, is the first large, multi-center, randomized clinical trial to determine whether red blood cell storage time affects the postoperative outcomes of heart surgery patients. Over one-half of heart surgery patients need at least one transfusion of red blood cells, accounting for a large portion of red cell transfusions in the United States.
"Only through randomized, controlled clinical trials such as RECESS will we be able to determine whether the age of stored red blood cells affects patient outcomes," said George Nemo, Ph.D., NHLBI program officer for the Transfusion Medicine/Hemostasis Clinical Trials Network, which is conducting the trial.
The trial, part of the Transfusion Medicine/Hemostasis Clinical Trials Network, is led by principal investigator Marie Steiner, M.D., associate professor at the University of Minnesota Medical School, and will be conducted at multiple sites across the country, including Atlanta; Baltimore; Boston; Chapel Hill, N.C.; Durham, N.C.; Iowa City, Iowa; Minneapolis; New York City; New Brunswick, N.J.; Pittsburgh; and Seattle. Participants will be randomly assigned to receive blood that was stored for 10 or fewer days, or blood that was stored for 21 or more days. Researchers will track the participants' health and compare outcomes between the two groups, such as death rates one month following surgery; post-operative complications such as stroke, heart attack, kidney failure, pulmonary embolism (blockage of an artery in the lungs), and sepsis (a life-threatening infection); and the need for mechanical ventilation.
RECESS plans to enroll about 1,830 patients. Most RECESS sites expect to begin enrolling patients in early summer 2010, although additional sites may be added later. More information about the trial (NCT00991341) can be found at http://clinicaltrials.gov/.
Eight Grants for Blood Storage and Preparation
The NHLBI is also supporting eight different studies that will examine what changes red blood cell units undergo when they are prepared and stored, as well as whether those changes affect the blood vessels and tissues once transfused.
"These studies will lead to a better understanding of the changes that occur as a function of red blood cell preparation and storage time and their effect, if any, when transfused," said Simone Glynn, M.D., chief of the Transfusion Medicine and Cellular Therapeutics Branch in the NHLBI's Division of Blood Diseases and Resources. "The results of this work could lead to improved red blood cell therapies that optimize tissue oxygen delivery in transfusion recipients."
Blood breaks down the longer it is stored. Some red blood cells disassociate, releasing their hemoglobin—the iron-rich protein that carries oxygen. The free hemoglobin joins a growing collection of microparticles, white blood cell residues, and other byproducts that are contained in a fluid called the supernatant. Many of the red blood cells that stay intact develop membrane damage and lose their flexibility. Research is needed to determine whether such physical and biochemical changes adversely affect patients who receive stored blood.
In addition, researchers have yet to tease apart the effects of blood storage, blood components, the amount of blood transfused, genetics, and illness or injury on the patient's health after a transfusion. For instance, people with sickle cell disease, the blood disease thalassemia, and other chronic conditions that require frequent transfusions are at higher risk of transfusion complications.
"Until now, few projects have tried to distinguish complications that may result from the patient's underlying illness from those that may arise from the transfusions themselves," said Glynn.
The findings could open opportunities for personalized transfusions, where blood products could be manipulated based on a person's specific disease or characteristics. For example, if researchers discover that people with sickle cell disease suffer complications from a certain component of transfused blood, then those patients could be given red blood cell transfusions devoid of that component.
The eight grants are:
A list of hospitals participating in RECESS can be found at http://clinicaltrials.gov/ (NCT00991341). Patients who have cardiac surgery scheduled at one of these hospitals and who are interested in participating in RECESS are encouraged to discuss the study with their physician. Physicians or medical centers who are interested in participating as a trial site can contact the RECESS Data Coordinating Center by e-mail (email@example.com) or phone (617-972-3197) for more information.
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at http://www.nhlbi.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.