National Heart, Lung, and Blood Institute Funds Research to Improve Safety of Red Blood Cell Transfusions
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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."
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.
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."
The eight grants are:
-- "Storage lesion in banked blood due to disruption of nitric oxide homeostasis," Mark Gladwin, M.D., University of Pittsburgh, and Daniel Kim-Shapiro, Ph.D., Wake Forest University, Winston-Salem, N.C. This team proposes that transfusion damage from stored blood can be traced to reduced levels of nitric oxide, a chemical that causes blood vessels to expand so that they can take in more oxygen. The team will study whether microparticles and free hemoglobin released from ruptured red blood cells in stored blood soaks up the nitric oxide that patients need.
-- "RBC age and potentiation of transfusion related pathology in trauma patients," Rakesh Patel, Ph.D., Scott Barnum, Ph.D., and Jordan Weinberg, M.D., University of Alabama at Birmingham. Studying injured patients in an intensive care unit who need one transfusion of red blood cells, this group will investigate how red blood cell storage time affects blood flow through capillaries, and how this blood flow is affected by the interaction between banked blood and both nitric oxide and the immune system.
-- "Adverse effects of RBC transfusions: A unifying hypothesis," John Roback, M.D., Ph.D., Emory University, Atlanta. Roback's team will study how red blood cell storage time and preparation methods (including irradiation and white blood cell removal) change nitric oxide levels, blood flow, and the amount of oxygen absorbed by patients' tissues. It will also investigate whether cardiovascular disease patients who have trouble making nitric oxide are more sensitive to the effects of stored and processed blood than they are to fresh blood. More information about this clinical trial (NCT00838331) can be found at <http://clinicaltrials.gov/>.
-- "Restoration and function of S-nitrosothiol in stored blood," Jonathan S. Stamler, M.D., Case Western Reserve University and University Hospitals, Cleveland, Ohio. Stamler's team previously discovered that red blood cells regulate blood flow by dilating blood vessels, and that a mediator of this response called S-nitrosohemoglobin (SNO-Hb), falls in stored blood. The researchers will determine whether restoring SNO-Hb levels in stored blood prior to transfusion will improve tissue oxygenation.
-- "Identification and significance of biologic mediators in red cell concentrates," Neil Blumberg, M.D., and Richard P. Phipps, Ph.D., University of Rochester, N.Y. This team will investigate red blood cell units' supernatant, including hemoglobin, microparticles, and fats. The team will investigate what changes the supernatant undergoes, what effects it and the stored red blood cells have on patients' platelets, and whether salt-water washing or other methods reverse those effects.
-- "Microparticles in stored RBC as potential mediators in transfusion complications," Wenche Jy, Ph.D., University of Miami, Fla. Jy's team will be the first to explore the role of red blood cell microparticles in transfusion complications including clotting, inflammation, immune suppression, and endothelial tissue disruptions. In addition to conducting lab tests, the team will compare results from transfused patients given either blood stored under standard conditions or blood that was washed to remove microparticles prior to storage.
-- "Properties of stored RBCs: Minimization of immune and vascular reactivity," Philip Norris, M.D., Blood Systems Research Institute, San Francisco. Norris' team will focus on the immune effects of stored versus fresh red blood cells. In the lab, they will measure the role of storage time on red cell-endothelial cell adhesion, microparticles, and markers of inflammation. In the clinic, they will compare immune and inflammatory responses in critically ill patients who receive either standard transfusions (no storage time specified) or red blood cells that have been stored for fewer than eight days.
-- "Harmful effects of transfusion of older stored red cells: Iron and inflammation," Steven L. Spitalnik, M.D., Columbia University, New York City Spitalnik's team will determine if hemoglobin iron, which is released after transfusion from damaged red blood cells that have been stored longer, triggers an intense inflammatory response that is particularly harmful to patients with hemoglobin disorders (hemoglobinopathies) such as sickle cell disease and beta-thalassemia.
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."
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.
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."
The eight grants are:
-- "Storage lesion in banked blood due to disruption of nitric oxide homeostasis," Mark Gladwin, M.D., University of Pittsburgh, and Daniel Kim-Shapiro, Ph.D., Wake Forest University, Winston-Salem, N.C. This team proposes that transfusion damage from stored blood can be traced to reduced levels of nitric oxide, a chemical that causes blood vessels to expand so that they can take in more oxygen. The team will study whether microparticles and free hemoglobin released from ruptured red blood cells in stored blood soaks up the nitric oxide that patients need.
-- "RBC age and potentiation of transfusion related pathology in trauma patients," Rakesh Patel, Ph.D., Scott Barnum, Ph.D., and Jordan Weinberg, M.D., University of Alabama at Birmingham. Studying injured patients in an intensive care unit who need one transfusion of red blood cells, this group will investigate how red blood cell storage time affects blood flow through capillaries, and how this blood flow is affected by the interaction between banked blood and both nitric oxide and the immune system.
-- "Adverse effects of RBC transfusions: A unifying hypothesis," John Roback, M.D., Ph.D., Emory University, Atlanta. Roback's team will study how red blood cell storage time and preparation methods (including irradiation and white blood cell removal) change nitric oxide levels, blood flow, and the amount of oxygen absorbed by patients' tissues. It will also investigate whether cardiovascular disease patients who have trouble making nitric oxide are more sensitive to the effects of stored and processed blood than they are to fresh blood. More information about this clinical trial (NCT00838331) can be found at <http://clinicaltrials.gov/>.
-- "Restoration and function of S-nitrosothiol in stored blood," Jonathan S. Stamler, M.D., Case Western Reserve University and University Hospitals, Cleveland, Ohio. Stamler's team previously discovered that red blood cells regulate blood flow by dilating blood vessels, and that a mediator of this response called S-nitrosohemoglobin (SNO-Hb), falls in stored blood. The researchers will determine whether restoring SNO-Hb levels in stored blood prior to transfusion will improve tissue oxygenation.
-- "Identification and significance of biologic mediators in red cell concentrates," Neil Blumberg, M.D., and Richard P. Phipps, Ph.D., University of Rochester, N.Y. This team will investigate red blood cell units' supernatant, including hemoglobin, microparticles, and fats. The team will investigate what changes the supernatant undergoes, what effects it and the stored red blood cells have on patients' platelets, and whether salt-water washing or other methods reverse those effects.
-- "Microparticles in stored RBC as potential mediators in transfusion complications," Wenche Jy, Ph.D., University of Miami, Fla. Jy's team will be the first to explore the role of red blood cell microparticles in transfusion complications including clotting, inflammation, immune suppression, and endothelial tissue disruptions. In addition to conducting lab tests, the team will compare results from transfused patients given either blood stored under standard conditions or blood that was washed to remove microparticles prior to storage.
-- "Properties of stored RBCs: Minimization of immune and vascular reactivity," Philip Norris, M.D., Blood Systems Research Institute, San Francisco. Norris' team will focus on the immune effects of stored versus fresh red blood cells. In the lab, they will measure the role of storage time on red cell-endothelial cell adhesion, microparticles, and markers of inflammation. In the clinic, they will compare immune and inflammatory responses in critically ill patients who receive either standard transfusions (no storage time specified) or red blood cells that have been stored for fewer than eight days.
-- "Harmful effects of transfusion of older stored red cells: Iron and inflammation," Steven L. Spitalnik, M.D., Columbia University, New York City Spitalnik's team will determine if hemoglobin iron, which is released after transfusion from damaged red blood cells that have been stored longer, triggers an intense inflammatory response that is particularly harmful to patients with hemoglobin disorders (hemoglobinopathies) such as sickle cell disease and beta-thalassemia.
