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Understanding 'Transfusion Fevers'

A protein in platelets may be to blame

TUESDAY, June 26, 2001 (HealthDayNews) -- A protein that leaks out of blood cells as they're prepared for transfusion may explain why some patients getting blood develop fevers or life-threatening reactions, a new study suggests.

The researchers say the culprit may be the CD40 ligand protein, which is produced by platelets and which helps activate the immune system. Figuring out a way to gently separate platelets from other blood products during preparation of blood for transfusions could prevent the reactions, the researchers say.

"Millions of bags of platelets are given to patients each year -- for major surgery, for cancer patients, for patients having problems producing enough platelets," says study author Richard Phipps, professor of oncology, immunology, pediatrics and environmental medicine at the University of Rochester Cancer Center, in New York.

"The difficulty is in up to 30 percent of those transfusions; patients get these rather dramatic febrile responses -- chills and high fevers," indicating the immune system has been activated, Phipps says.

"In a small percentage of patients, they can get an acute and potent reaction causing fatal lung injury. The reasons for the febrile response have remained a mystery," he says.

Phipps says his insight into the protein's role in transfusion problems came during work that showed CD40 ligand could initiate the process that causes fever.

"Platelets themselves make the protein to protect the platelet and to regulate inflammation," he says. "When you're injured, this ligand is released from the cell and instigates inflammation in a regional fashion and that calls up the immune system."

Transfusion-reaction problems start with the process that separates platelet cells from donated blood, Phipps says. "These are delicate cells and to get these bags of platelets, blood is centrifuged or goes through a filter. Any of these processes sort of beat up the platelets. The process partially releases the cell's internal store of ligand."

"So picture you've got a bag of platelets with all this CD40 ligand spewed into the bag, and some on the surface of the cell as well," Phipps says. "When you give these platelets to a human being, they're getting all this CD40 ligand into their blood stream, and that kicks the immune system into high gear."

Platelets, along with white and red cells, are separated out of the blood because transfusions of "whole blood" can cause severe, even fatal reactions, Phipps says.

While fever from transfusions is usually mild and can be treated with over-the-counter acetaminophen, the reaction can mask other complications, Phipps says.

Phipps' findings were published in the June 23 issue of The Lancet.

Every year, approximately 40 million units of blood are donated by 23 million volunteers worldwide. And one of 20 people can expect to receive one or more of these life-saving transfused units, says the American Red Cross.

A Red Cross spokeswoman says the University of Rochester research offers a very good hypothesis that still needs to be proven.

"They would have to see if the levels of the CD40 ligand correlate with reaction severity," says Dr. Linda Chambers, the Red Cross' senior medical officer in Arlington, Va. "They would also need to see if these findings fit in with observations that we already know about febrile reactions to platelets."

What to Do: For more on blood and blood transfusions, check America's Blood Centers. To learn more about blood safety, visit the American Red Cross.

SOURCES: Interviews with Richard Phipps, Ph.D., professor of oncology, immunology, pediatrics and environmental medicine, University of Rochester Cancer Center, N.Y.; Linda Chambers, M.D., senior medical officer, American Red Cross, Arlington, VA; June 23, 2001 The Lancet
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