Transfusion Mystery Unraveled

UR Researchers Link Protein to Fevers, Immune Complications

June 22, 2001

University of Rochester Medical Center researchers have discovered why patients who receive blood-platelet transfusions often spike fevers or develop life-threatening complications. These patients, already very sick with cancer or who have undergone open-heart surgery or organ and bone marrow transplants, usually experience an array of difficult side effects that physicians must aggressively treat along with the underlying disease.

The new research, however, is the first to pinpoint the source of the transfusion-induced symptoms at the molecular level: A protein in the platelets escapes while the platelets are in storage and this leakage may ultimately be responsible for wreaking havoc on the body.

The research may also allow scientists to design a safer approach to the use of blood platelets.

"It would be nice to be able to pretreat the platelets so that patients only get the positive benefits and none of the negative ones," said Richard Phipps, Ph.D., professor of Oncology, Microbiology and Immunology, Pediatrics and Environmental Medicine. Phipps is co-author of the platelet research, published in the June 23 edition of the British medical journal, The Lancet.

"This finding may have repercussions in several areas," added Neil Blumberg, M.D., co-author and URMC professor of Pathology and Laboratory Medicine. "Not only does it explain one major mystery - fevers as a result of platelet transfusions - but it may help explain post-operative bacterial infections and other serious immune system complications."

Physicians have never been sure why patients develop fevers, chills, and a general sick feeling after receiving blood platelets intravenously. It is widely accepted that the side effects are either related to the underlying disease or to the way the body reacts to the white blood cells present in the transfusion. But the transfusions are necessary to correct a patient's reduced platelet count and promote blood clotting.

Physicians typically treat the side effects with fever-reducers such as Tylenol. There is no universal prophylactic treatment for the more serious side effects. In some cases, however, the white blood cells can be removed from the platelets before they are administered - but not even that always helps.

"Despite advances such as white-cell removal from platelet transfusions, we still see patients whose lives are miserable every time they get a transfusion," Blumberg said. "This work may provide a strategy for making side effects a thing of the past."

The new finding pins the problem on a protein in the platelets, called CD154 or CD40 ligand. When the protein escapes from platelet cells, it then makes contact with a receptor called CD40 once the platelets enter a patient's body. This "escape" is not supposed to happen, and the resulting compounds cause illness.

It is still unknown what activates the escape of CD40 ligand. It may stem from the way platelets are routinely separated from the blood, how they are stored, or their contact with foreign substances such as the plastic bags they are kept in, Phipps said. Ultimately, the researchers hope to find out how to prevent the leaking of the protein and design a safer approach to treating patients with transfusions.

A patent on the research is pending. The project was funded in part by the National Heart, Lung, and Blood Institute. A third author on the paper is Julia Kaufman, M.S., and a graduate student. The researchers are members of the James P. Wilmot Cancer Center at Strong Memorial Hospital.

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