Study in Science Suggests Method to Refigerate Platelets;
Process May Ease Shortages for Transfusions

A new method for treating and chilling blood platelets may prolong their shelf-life by a week or more, helping to ease chronic shortages that endanger patients needing platelet transfusions. These findings appear in the 12 September issue of the journal Science, published by AAAS, the science society. AAAS and the American Medical Association held a joint press conference on the new research findings on the morning of Thursday, 11 September, at the Park Hyatt Philadelphia.

Platelets, the cell fragments in blood that help make clots to stop bleeding, must currently be stored at room temperature for a limit of five days. After this period, the platelets must be thrown away, because they no longer function properly and their risk of bacterial contamination increases sharply.

Shortages in donated platelet supplies can have serious consequences, because patients awaiting platelet transfusions need them urgently. These patients are typically bleeding severely, after major surgeries or accidents, or they may have undergone chemotherapy or bone marrow transplants.

Karin Hoffmeister of Brigham and Women's Hospital and Harvard Medical School, and one of the lead authors of the Science study, expects the need for platelets to increase in the future. Thomas Stossel of Brigham and Women's Hospital and Harvard Medical School is the other lead author.

"As the population gets older, we need more and more donations. And the number of younger donors is shrinking. The blood banking industry loses a significant amount of money by throwing these bags of platelets away," Hoffmeister said.

Chilling the platelets helps lengthen their storage period, but these platelets die quickly once they are transfused into the body. Using mice and human platelets in test tubes, Hoffmeister, Stossel, and their colleagues have found a way to extend the lives of chilled platelets after transfusion. If the method works for human patients, it could increase the platelet supply and make this blood component easier to transport.

"This research could ultimately help more patients receive life-saving platelet transfusions. The authors started with an interesting question about human biology, and came up with a technique that could truly benefit society," said Dr. Alan Leshner, CEO of AAAS, the science society, and Executive Publisher of Science.

"Blood banks have long needed ways to preserve the function of refrigerated platelets so that they are suitable for transfusion. This research represents an important step toward that goal," said Katrina Kelner, Science's Deputy Editor for the life sciences.

When platelets are chilled down to around four degrees C, the temperature needed for preserving them beyond five days, it causes certain receptors on their surface to cluster together.

After transfusion, the immune system's cellular vacuum cleaners, the macrophages, detect these clusters and ingest the platelets, destroying them.

Hoffmeister, Stossel, and their colleagues in the United States, Sweden, and Denmark found a way to mask the specific sugar molecule that the macrophages recognize in the receptor cluster.

By adding a single substance to a supply of platelets, the researchers induced a reaction that stacked a different sort of sugar molecule on top of the platelet receptor's tell-tale sugar. This treatment seemed to be effective either before or after the platelets were refrigerated, and allowed transfused platelets to evade detection by the macrophages after up to 12 days of storage.

Twenty-four hours after being transfused into mice, the number of chilled, treated platelets remaining in the blood stream was approximately 30 percent higher than the number of room temperature platelets that remained. In contrast, untreated, chilled platelets diminished rapidly after transfusion, Hoffmeister and her colleagues report.

In test tube experiments with human platelets, the treatment also prevented much of the destruction that macrophages inflicted upon untreated, chilled platelets, according to Hoffmeister.

The treatment consists of adding a sugar compound, called UDP galactose, which certain blood enzymes use to hook sugars together. UDP galactose already exists in human cells and body fluids, and the researchers are optimistic that adding it to platelet supplies will not harm patients receiving transfusions.

Nonetheless, further studies are needed to determine whether this method will be safe and effective in humans.

Hoffmeister and Stossel's co-authors are Emma C. Josefsson, Natasha A. Isaac, and John H. Hartwig, at Brigham and Women's Hospital, Harvard Medical School, in Boston, MA; E. Josefsson is also at University of Gothenburg, in Gothenburg, Sweden; Henrik Clausen, at University of Copenhagen in Copenhagen, Denmark, and Zymequest, Inc., in Beverly, MA. The study was funded by the U.S. National Institutes of Health, the Edwin S. Webster and Ellison Foundations, the American Cancer Society, and the Danish Research Council.

—Kathy Wren

11 September 2003