The Problem with Transfusions

By Alice Park

it's been called the gift of life, and for the 5 million people in the U.S. who receive blood transfusions each year, it's a gift gratefully accepted. But what if banked blood, always a beacon of hope and health, may also do serious harm?

That's a possibility that doctors have been wrestling with for several years, as studies have shown a disturbing spike in heart attacks--as much as 25%--and even deaths in patients who have received blood, usually within a month after the transfusion. The problem may occur to some degree in almost every group of critically ill patients, from trauma cases in the E.R. to anemics in the icu. Since doctors know how to safeguard the blood supply from infectious diseases and keep allergic reactions from transfusions to a minimum, the heart-attack problem doesn't seem to be related to either of those risks.

"Even after you control for sickness and all sorts of things, patients who receive transfusions still have more heart attacks. It makes no sense," says Dr. Jonathan Stamler, a professor of medicine at Duke University Medical Center. But Stamler and his colleague Dr. Timothy McMahon may at last have an explanation. In studies reported in Proceedings of the National Academy of Sciences, they sampled pints of donated blood from banks and healthy volunteers, subjected them to 26 different analyses and found dramatic deficiencies in levels of nitric oxide (NO). A workhorse component of normal blood, NO is responsible for helping red blood cells ferry oxygen to tissues and for propping open tiny vessels. A shortage of the gas could lead to precisely the kinds of heart problems the team was investigating.

Within hours of leaving the body, the research showed, a unit of blood loses up to 70% of its NO; by the time the blood reaches its "use by" expiration date 42 days later, the gas is almost nonexistent. "The reality is, we are giving patients blood that cannot deliver oxygen properly," says Stamler.

The consequences of this seem clear from the numbers. A study of 24,000 people with acute coronary symptoms showed that those who received a blood transfusion had a 25% chance of having a heart attack and an 8% chance of dying within 30 days; similar patients who did not get a transfusion had an 8% chance of a cardiac event and a 3% chance of death. Stamler believes that without NO, red blood cells are not dilating tiny vessels properly and instead pile up in the narrow passageways, blocking flow and damaging the very heart tissue the blood was transfused to help.

While donor blood alone may not be directly responsible for this added risk, those percentages had already been disturbing enough to persuade physicians to change what is known as their transfusion trigger. As a rule, they introduced donated blood as soon as the patient's hematocrit--a measure of the proportion of the blood made up of oxygen-carrying red cells--fell below the normal range of 45%-55%. Lately, however, they have begun waiting until it drops to less than 30% before transfusing.

The new study makes this revised standard look all the smarter. "There is still a lot of controversy about the trigger," says Dr. Lynne Uhl, a transfusion specialist at Beth Israel Deaconess Hospital in Boston. "But the growing data have reinforced the practice that it's O.K. to let the patient's hematocrit drop lower before transfusing."

Another answer may be to fix the blood that's on the shelves. Working with dogs, Stamler has shown that the heart-attack rate drops when depleted blood is replenished with liquid NO. Human premature babies born with underdeveloped lungs are already being exposed to gaseous NO to help their tissues get the oxygen they need. For now, the American Red Cross, which oversees the 14 million units of stored blood, is awaiting more studies before changing its processing and storage practices.

For their part, Stamler, who consults for a company developing NO-based therapies, and McMahon, whose work was funded in part by another such firm, are thinking about using transfusions of NO-fortified donor blood to treat such ills as heart disease, stroke and diabetes. "We want to open up blood vessels, and blood knows how to do that," he says. Perhaps a nitric oxide boost would help it do its job even better.