Two US studies suggest that almost as soon as it has been donated, banked human blood loses the vital ability to transfer oxygen to body tissue that desperately needs it. The researchers say that for the majority of patients, blood transfusions with banked human blood could do more harm than good.
The studies are to be published in the early online issue of the Proceedings of the National Academy of Sciences (PNAS) and are the work of two teams of scientists at Duke University Medical Center in Durham, North Carolina.
Almost immediately after it leaves the body, human blood begins to lose an essential gas, nitric oxide which is believed to be crucial to the delivery of oxygen to tissues because it keeps the tiny blood vessels inside the tissue mass open. The researchers also believe that it helps red blood cells to stay flexible so they can easily fit into the narrow constraints of the blood vessels.
The last five years has seen a number of studies, some of which were carried out at Duke’s, showing that patients who received blood transfusions had higher rates of heart attack, heart failure, stroke, and even death. But while scientists knew that banked blood was not the same as the blood in the body they did not know why it should carry these risks.
Th Duke researchers have also carried out early experiments using dogs to show that adding nitric oxide to banked blood restores its ability to deliver oxygen. It now needs to be proved in humans through clinical trials said the researchers.
Senior author of one of the papers, Dr Jonathan Stamler, George Barth Geller Professor for Research in Cardiovascular Diseases at Duke’s said:
“It doesn’t matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide.”
Stamler’s team originally discovered the importance of nitric oxide to the delivery of oxygen from red blood cells.
“Nitric oxide opens up the tiny blood vessels, allowing red blood cells to pass and deliver oxygen. If the blood vessels cannot open, the red blood cells back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death,” said Stamler.
According to the new studies, nitric oxide in red blood cells starts to break down soon after red blood cells leave the body.
“The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine,” explained Stamler.
While blood transfusions are critically important, and banked blood can be a life saver, there are times when it can make things worse. Having this knowledge about nitric oxide, which still needs to be proven in humans through clinical trials, means “in principle, we now have a solution to the nitric oxide problem,” he added.
Nearly 5 million Americans receive about 14 million units of red blood cells every year, the researchers said, according to estimates.
Donated blood has to be used within 42 days of donation. After that unused blood has to be discarded. “Banked blood is truly a national treasure that needs to be protected,” said Stamler.
The other study on the role of nitric oxide in banked blood that is to be published in PNAS was also carried out by Duke researchers, led by associate professor of pulmonary medicine, Dr Timothy McMahon.
McMahon’s group studied the changing properties of banked blood during the 42 days of storage. They tested human blood that was being kept according to the national standards for the storage of banked blood by taking samples at regular intervals.
They were surprised at how quickly it changed, said McMahon:
“We saw clear indications of nitric oxide depletion within the first three hours.”
“Of concern to us is that nitric oxide levels become depressed soon after collection, suggesting that even “fresh” blood may have adverse biological characteristics,” he added.
They discovered that as well as being essential for offloading oxygen to tissue, nitric oxide also plays a part in keeping red blood cells flexible. As the levels of nitric oxide recede, so the saucer shaped cells get stiffer, so they don’t bend and flex easily into the narrow blood vessels in the tissue.
To test whether putting nitric oxide back into the stored blood would affect its ability to supply oxygen, Stamler and his team used dogs.
They showed that when they gave stored blood to the oxygen deprived animals, the blood flow did not increase properly. Yet paradoxically stored blood is often given to heart patients to prevent heart attacks. This experiment showed that doing this could actually be increasing the risk of a heart attack.
When they added nitric oxide to the stored blood they gave to the dogs, blood flow to the heart was increased, indicating the blood vessels were sufficiently dilated to allow passage of the blood cells and oxygen transfer to take place.
“This suggests that adding nitric oxide to human banked blood could theoretically improve its ability dilate blood vessels and thus prevent heart attacks and even death in patients,” said the researchers.
A large-scale randomized clinical trial in humans is needed, said McMahon and Stamler. These studies show that donated blood has risks as well as benefits, and therefore should undergo clinical trials in the same way as drugs and medication.
There is no doubt that transfused blood can be harmful, they said. In any medical treatment, there are benefits and there are risks. In the case of banked blood, the risks now need to be properly evaluated:
“We are only uncertain about how serious the problem is,” said Stamler.
“The availability of a potential solution will hopefully focus the attention of the medical community on the potential magnitude of this problem,” he added.
“S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood.”
James D. Reynolds, Gregory S. Ahearn, Michael Angelo, Jian Zhang, Fred Cobb, and Jonathan S. Stamler.
Published 11 October 2007, 10.1073/pnas.0707958104
“Evolution of adverse changes in stored RBCs.”
Elliott Bennett-Guerrero, Tim H. Veldman, Allan Doctor, Marilyn J. Telen, Thomas L. Ortel, T. Scott Reid, Melissa A. Mulherin, Hongmei Zhu, Raymond D. Buck, Robert M. Califf, and Timothy J. McMahon.
Published 11 October 2007, 10.1073/pnas.0708160104
Written by: Catharine Paddock