HARVARD GAZETTE ARCHIVES
A cold-blooded solution:
Sugarcoating may improve platelet transfusion
By William J. Cromie
Harvard News Office
Blood is vital for human survival, but getting it to people who need it involves thorny problems.
Blood platelets, which are transfused into those who lose too much blood from wounds, major surgery, or cancer treatments, can be kept for only five days. Then they must be discarded, a waste of hundreds of millions of dollars a year. Refrigeration can extend the shelf life to about a month, but when this cold blood is put into a body, the platelets disappear almost instantly.
A team of Harvard Medical School researchers, working at Brigham and Women's Hospital in Boston, has discovered why cold blood doesn't work, and has used that knowledge to get it working.
The resulting technology promises to generate a new force for saving lives all over the world. "If further development is successful, this technology could have a major impact on platelet transfusion therapy by simplifying blood storage, prolonging storage time, solving problems for maintaining platelet supplies for transfusion, improving platelet quality, and contributing to platelet safety," says Thomas Stossel, a Harvard professor of medicine.
The breakthrough is the cover story of the September 12 issue of Science, one of the world's most prestigious science journals. Lead author of the report (the person who did most of the work) is Karin Hoffmeister, who works in Stossel's laboratory.
Sticking and chilling
When you bleed from a cut or major external or internal wound, platelets in your bloodstream rush to the site. They stick to the surface of broken blood vessels and plug the leak.
A low stock of platelets is a common and often fatal complication in patients suffering major trauma or undergoing cancer treatment or surgery in hospitals and on battlefields. Transfusions of platelets are often necessary to stop bleeding and save the lives of such patients.
Fresh, warm platelets keep working for about a week after a transfusion. But when the cells are refrigerated to retard spoilage by bacteria or a buildup of toxic waste products, the liver attacks and destroys them. The dilemma makes it extremely difficult for blood supply services to keep on hand enough platelets to cover a highly unpredictable demand. If they keep too much, the unused portion must be thrown away; if not enough, patients could die.
This system encourages use of the oldest platelets, and these cells may be of the poorest quality.
Stossel points out that "with an aging population and greater use of cancer treatments and major surgery, the demand keeps growing and the system is under strain." (Cancer chemotherapy involves drugs that lower platelet counts.)
Hoffmeister, Stossel, John Hartwig, and others in their research group set themselves the task of finding out why chilled platelets can't do the same work as their warm relatives.
First, they found that scavenger cells in the liver eat platelets that have been refrigerated but not those that weren't chilled. A closer look at this puzzling behavior showed that platelets carry a sticky spot called a receptor, and chilling causes such receptors to ball up or cluster. Scavenger cells find these clusters irresistible and they eat the platelets.
Why would this be so? The research team speculates that the mechanism involves a natural protective response. The severest bleeding risk to humans and other animals comes from surface wounds, where body temperatures are coolest. Through evolution, a system developed to quickly get rid of the cooled platelets, which might cause unwanted blood clotting in undamaged parts of the body.
A sweet change
The job that Hoffmeister's team then set for itself was to somehow change the sticky receptors so platelets could circulate freely.
Their next discovery was that a certain sugar on the receptors is responsible for attracting scavenger cells. If these sugars could be hidden somehow, the scavengers might leave the platelets alone.
Sure enough. During experiments in mice, when they covered the attractive sugar with a neutral sugar, chilled platelets worked as well as those kept at room temperature.
The sugar modification technique "is extremely simple," Stossel explains. "We simply add to platelets obtained from a donor a sugar compound normally found in the body. The modification can be performed before or after refrigeration of platelets, and it is stable during two weeks of storage."If the technique works as well in humans as it does in mice, it will inject new life into transfusion therapy the way platelets can inject new life into wounded and sick people.