Store donated blood for more than three weeks? Say NO (nitric oxide)

March 10, 2013

Transfusion of donated blood more than three weeks old results in impaired blood vessel function, a new study of hospital patients shows. Blood banks now consider six weeks to be the maximum permitted storage time of blood for use in transfusion, but recent studies have suggested transfusing blood stored for more than a few weeks has adverse effects in patients undergoing cardiac surgery or critical care.

The new finding suggests a mechanism explaining why older blood might be detrimental to patient health: a deficiency in nitric oxide, a short-lived that relaxes blood vessels.

The results are being presented at the American College of Cardiology meeting in San Francisco. The presenter is cardiovascular research fellow Robert Neuman, MD. Senior authors include Arshed Quyyumi, MD, professor of medicine and director of the Emory Clinical Cardiovascular Research Institute, and John Roback, MD, PhD, associate professor of pathology and laboratory medicine and medical director of the Emory University Hospital blood bank.

In the current study, 43 patients at Emory University Hospital were set to receive cross-matched red for clinical indications. Members of the group were in hospital for various reasons, such as and surgery. They were randomly chosen to receive either fresh (less than ten days old) or aged (more than three weeks old) red blood cells. On average, they received the equivalent of two units. A unit is 450 milliliters of blood.

Neuman and his colleagues tested blood vessel function by measuring flow-mediated dilation (FMD). By ultrasound, they tested how much a blood vessel in the arm opens up after a blood pressure cuff is first tightened then removed. Flow-mediated dilation is an indicator of the health of the endothelial lining of the blood vessels and is a process that is dependent on nitric oxide.

Healthy, younger individuals can have flow-mediated dilation of up to 10 percent – the average for the hospitalized group was 5 percent. Patients receiving aged blood saw their FMD halved to 2.4 percent 24 hours after the transfusion, while patients receiving fresh blood saw no significant change in FMD.

This effect of older blood on blood vessel function is similar in size to that of eating a fatty meal (temporary), or the longterm effects of a cardiovascular disease risk factor such as smoking or diabetes.

Healthy flow-mediated dilation reflects sufficient production of nitric oxide, which is generated by the ' endothelial lining and causes them to relax. Nitric oxide is also important for delivery of oxygen by hemoglobin. Red blood cells carry nitric oxide bound to hemoglobin, and play a critical role in recycling the nitric oxide. Over time in storage, the nitric oxide is lost. Transfused red blood cells last a couple months in the patient. The Emory team did not measure FMD beyond 24 hours.

The so-called "red blood cell storage lesion" consists of several changes including oxidation, disruption of cellular structures, and loss of other chemicals such as the energy currency ATP and the hemoglobin regulator 2,3-diphosphoglycerate. A recent study has also shown that red blood cells stored for more than three weeks lose physical flexibility.

Thus, loss of nitric oxide is probably not the only important change, but it may be significant in terms of effects on cardiovascular health, the authors argue.

"Aside from the direct infusion of nitric oxide-deficient blood, we may be also seeing an indirect effect from other aspects of storage that impact nitric oxide availability and endothelial function such as increased inflammation triggered by aged blood," Neuman says.

A 2008 study published in the New England Journal of Medicine found that patients receiving older blood had a higher risk of dying in the hospital, and were more likely to need ventilation support or have sepsis or kidney failure. Two large-scale clinical trials (links below) are addressing the issue of the maximum time blood should be stored.

Although blood banks tend to use a "first-in, first-out" policy, limiting storage time could reduce the blood supply. One possibility could be to reserve fresh blood for those patients at most risk of cardiovascular problems, Neuman says.

Another way that nitric oxide deficiency could be remedied is with an additive such as nitrite, which the body uses as a storage reservoir for , or some other preservative. are now stored in a solution with glucose, anticoagulant and acidity buffering properties.

"There is a lot of information that that has been stored for a while can cause problems for patients," Neuman says. "This starts to answer the question: what is causing the problem?"

Explore further: Team finds why stored transfusion blood may become less safe with age

More information: Clinical trials going on now addressing the blood storage time issue:
ABLE = age of blood evaluation (www.ncbi.nlm.nih.gov/pubmed/21550205)
RECESS = red cell storage duration study (clinicaltrials.gov/show/NCT00991341)

Related Stories

Team finds why stored transfusion blood may become less safe with age

July 13, 2011
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, say researchers at the University of Pittsburgh ...

Discovery opens new options for improving transfusions

July 15, 2011
Donated red blood cells lose a key feature that diminishes their lifesaving power the longer they have been stored, according to researchers at Duke University Medical Center.

Discovery of nitric oxide delivery mechanism may point to new avenue for treating high blood pressure

November 14, 2012
(Medical Xpress)—Researchers at the University of Virginia School of Medicine have shed new light on blood pressure regulation with the discovery of an unexpected mechanism by which hemoglobin controls the delivery of nitric ...

Non-alcoholic red wine may help reduce high blood pressure

September 6, 2012
Men with high risk for heart disease had lower blood pressure after drinking non-alcoholic red wine every day for four weeks, according to a new study in the American Heart Association journal Circulation Research.

Nitric oxide impacts source of sickle cell pain crisis

May 9, 2011
Nitric oxide gas appears to directly impact the source of the classic, disabling pain crises of sickle cell disease, Georgia Health Sciences University researchers report.

Recommended for you

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Brain cells found to control aging

July 26, 2017
Scientists at Albert Einstein College of Medicine have found that stem cells in the brain's hypothalamus govern how fast aging occurs in the body. The finding, made in mice, could lead to new strategies for warding off age-related ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

dogbert
1 / 5 (1) Mar 11, 2013
Even though we have known for a long time that blood loses effectiveness during storage, there is no method by which you may give fresh blood to someone you want to help. Try it. The hospital may accept your blood as a replacement for blood the person receives (or suggest you donate to their blood bank), but the person you want to help will only receive older blood donated by someone else.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.