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Conversion makes all blood type O

New technique could stretch blood bank inventories by removing A and B molecules

Emergency medical situations require universal, type O blood supplies. Emergency medical situations require universal, type O blood supplies. (ISTOCKPHOTO)
Email|Print|Single Page| Text size + By Jennifer Cutraro
Globe Correspondent / March 24, 2008

Savvy shopkeepers know to put the oldest milk cartons at the front of the grocery-store shelf. In a similar way, blood banks around the country make the most efficient use of their blood supply by using their oldest units of blood first in transfusions.

But a recent study in the New England Journal of Medicine suggests cardiac patients receiving blood that is more than two weeks old suffer greater risks of complications such as kidney failure. While the study does not recommend changing current practices, it underscores a persistent challenge that blood banks face: how to increase blood turnover and avoid wasting unused and less-common blood types.

One local biotech company might have at least a partial solution to the problem: ZymeQuest Inc., in Beverly, has developed a technology that converts all blood types to O, the universal donor.

The technology could remove some of the logistical and inventory challenges confronting blood-banking services around the country, said Christopher Stowell, director of the Massachusetts General Hospital Blood Transfusion Service, who has no connection to the company.

"The margin between donation and need is pretty thin, so conversion would certainly be a convenience," said Stowell, also an assistant professor of pathology at Harvard Medical School. "O is the blood type we use in emergency situations when we don't have time to check a patients' blood type. The O units are, for that reason, always in tight supply."

Simple sugar molecules on the surface of red blood cells determine a person's blood type. One type of sugar molecule indicates type A blood, another indicates type B blood, and individuals with both sugars on their blood cells have the blood type AB. Individuals who lack all of these sugars - roughly 40 percent of the population - have blood type O.

The body's immune system recognizes its own sugar molecules, but sees sugars of another type as foreign invaders. That's why a person with type A blood can't receive a transfusion from someone with type B blood: The type A immune system would attack the new blood as foreign, making the person gravely ill.

Because type O blood carries neither of these sugars, it sails undetected right past the immune systems of type A, B, and AB individuals. For this reason, patients with any blood type can receive type O blood.

The ZymeQuest system uses enzymes isolated from bacteria to strip those A and B sugars off the surface of red blood cells, said Henrik Clausen, a scientific consultant to the company and professor of molecular medicine at the University of Copenhagen in Denmark. Then the red blood cells are washed with a saline solution to remove the enzymes and chopped-off sugars using a cell-washing device designed and built by ZymeQuest. The device can simultaneously process 8 units of blood, of 500 milliliters each.

"It's a fairly simple process," Clausen said. "The key obstacle is to find enzymes with the right specificity so that they take off only the one sugar and leave other molecules on the cell surface intact."

The hunt for blood-converting enzymes goes back more than 25 years, when a researcher at the New York Blood Center discovered he could cleave the B-type sugar off red blood cells using an enzyme he isolated from unroasted green coffee beans, then safely transfuse these cells into people, Clausen said.

ZymeQuest obtained the intellectual property behind this technology, but because these coffee-based enzymes do not very efficiently convert blood, Clausen began searching eight years ago for other enzymes that would work better at room temperature and a neutral pH.

"We didn't know if enzymes with these properties even existed in nature," he said. So he and his colleagues scanned 2,500 bacterial and fungal sources for enzymes that might do the job. They found a few contenders with specific abilities to recognize and snip apart the connection holding A and B sugars to the surface of red blood cells, and are now incorporating these enzymes into their blood conversion system.

ZymeQuest is in the early stages of phase 2 clinical trials with both type A and type B conversion systems, said chief financial officer Tom Fitzgerald. He expects their technology to be in the trial and testing phase for at least three to four more years. It's not yet clear, he said, how much the final process will cost per pint of blood.

Dr. Richard Benjamin, chief medical officer at the American Red Cross national headquarters in Washington, said he's been following ZymeQuest's progress for about five years.

"The technology has obstacles that the company has to deal with. It's not as simple as we originally thought it might be," Benjamin said. "Whether the system in development is going to be practical and cost effective, only time will tell."

And even if the technology is perfected, he said, there's not a lot of extra type O blood in the blood supply waiting to be transformed. Only about 3 percent of all donated blood is wasted nationwide, according to the 2005 Nationwide Blood Collection and Utilization Survey Report.

Steve Sloan, director of pediatric transfusion medicine at Children's Hospital Boston, said he remains cautious about blood conversion.

"The fact is, when you modify cells, it can cause risks and changes that you don't expect," he said, pointing out that any such risks would likely become clear in clinical trials.

"It's a good technology in that it can increase our inventory of type O red cells," said Sloan, who has done work for ZymeQuest in the past. "But how expensive is that? And for the same cost, could we just recruit more blood donors to increase our supply of type O blood?"

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