Artificial Platelets Catalyze Clotting

16 December 2009 (All day)

J. Bertram et al., Science Translational Medicine

Platelet helper. Artificial platelets (green) crowd a blood clot.

Platelets can quickly stanch the bleeding from a cut in your finger, but the hemorrhaging caused by a car crash or a battlefield injury might overwhelm the blood-clotting abilities of these cell fragments. Now, researchers report that they have designed a potential helper for such situations, a synthetic platelet that they show can curtail blood loss in animals.

After an injury, platelets stick to the walls of damaged vessels, to each other, and to clotting proteins, forming a plug. Platelet transfusions can boost clotting in trauma patients, wounded soldiers, and people with low platelet counts because of disease or cancer treatment. But platelets obtained from donated blood have several drawbacks, including a shelf life of only 5 days--versus 6 weeks for red blood cells--and a risk of bacterial infections.

Researchers have devised replacement platelets, such as red blood cells outfitted with a three-amino-acid sequence called RGD that natural platelets latch on to, thus potentially inducing a clot. So far, none of these alternatives has reached the emergency room. "If there was a suitable platelet substitute, that would be a tremendous achievement for clinical medicine," says hematologist Marcel Levi of the University of Amsterdam in the Netherlands.

Six years ago, James Bertram, then a graduate student at Yale University, and colleagues started developing a substitute. Their design involves spheres about one-tenth the diameter of a platelet and made of the same biodegradable polyester used in absorbable sutures. The spheres carry molecules of polyethylene glycol--an ingredient in everything from laxatives to Dr Pepper--tipped with RGD or a slightly longer string of amino acids. The idea is that the spheres will adhere to platelets and help them congregate into a clot.

The researchers tested the spheres in rats with a cut in the femoral artery, the large vessel that carries blood into the hind leg. These wounds sealed themselves in about 4 minutes, but an intravenous injection of the synthetic platelets, given just after the cut, reduced the bleeding time by 23%, the researchers report today in Science Translational Medicine. The spheres crammed into the clot that formed at the site of the cut, the team found, suggesting that they help the animals' own platelets coalesce.

"It's one of the first times that we have been able to stop bleeding intravenously" rather than with measures like bandages and sutures, says senior author Erin Lavik, a biomedical engineer at Case Western Reserve University in Cleveland, Ohio. She notes that the U.S. Food and Drug Administration has already okayed the materials in the artificial platelets for other medical uses, which might make it easier to get the product approved. Lavik says that the team now wants to gauge the platelets' clotting capability in larger animals, such as pigs, that are more similar to humans.

Some experts call the results promising. "They have some potentially exciting, preliminary work," says hematologist Paul Ness of the Johns Hopkins Medical Institutions in Baltimore, Maryland. "I was quite impressed with the science," adds hematologist Morris Blajchman of McMaster University in Hamilton, Canada.

But John Hess, a hematologist at the University of Maryland School of Medicine in Baltimore and the former head of the U.S. Army's blood product development program, isn't sanguine. Patients suffering from severe bleeding are losing large amounts of platelets, so an approach that relies on recruiting platelets might not work, says Hess. "You might run out of platelets before you can control the hemorrhage."

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