McGowan Institute for Regenerative Medicine
faculty member Albert Donnenberg, Ph.D. (pictured), professor of infectious disease and microbiology in the Graduate School of Public Health and a professor of medicine in the School of Medicine at the University of Pittsburgh, was part of a multi-university team of researchers who found that transfused blood may need to be stored in a different way to prevent the breakdown of red blood cells that can lead to complications including infection, organ failure, and death. The team recently reported the latest findings from its ongoing exploration of the interaction between red blood cell breakdown products and nitric oxide (NO), revealing new biological mechanisms that can reduce blood flow and possibly damage vital tissues after administration of blood that has been stored for longer than 39 days.
In recent years, doctors have noted that transfusion of either many units of blood or of blood stored a long time may be associated with a greater frequency of complications, such as increased infection risk, kidney, lung, or multi-organ failure, and death, particularly among medically vulnerable patients, explained senior investigator Mark T. Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine, and director of Pitt’s Vascular Medicine Institute.
“When blood sits for a while, some of the cells break down and release their contents, which include molecules of hemoglobin and red blood cell microparticles,” he said. “These accumulate in the stored bag of blood and are transfused into the patient with the blood. In the bloodstream, the hemoglobin and microparticles bind to and destroy NO, a very important molecule that is used by the body to keep blood vessels dilated for normal blood flow.”
The scavenging of NO causes blood vessel constriction that can prevent tissues and organs from getting adequate oxygen and activate the platelets and the coagulation system, as well as cause inflammation, Dr. Gladwin said.
From their experiments, the university collaborators found that human blood stored under standard conditions accumulated “free” hemoglobin that was no longer contained in a cell and microparticles of damaged cells. Those breakdown products reacted with NO about 1,000 times more quickly than did intact red blood cells. Also, transfusion of even very low concentrations of hemoglobin caused blood vessel constriction and hypertension in a rat model.
Other research projects are underway to find approaches to correct the problem of storage lesion, and to assess the safety of blood for transfusion that has been stored for longer than 14 days. Currently, federal guidelines allow transfusion of blood that has been stored for up to 42 days.
Illustration: McGowan Institute for Regenerative Medicine.
University of Pittsburgh Schools of the Health Sciences Media Relations News Release (07/13/11)
Bio: Dr. Albert Donnenberg
Abstract (Circulation 2011; ahead of print, July 11, 2011.)