Genetic makeup can boost aspirin's benefit.

Platelets, the smallest blood cells, are indispensable. They work with other components of blood to form clots that prevent excessive bleeding. Unfortunately, "platelet cells are pretty stupid," says cardiologist Pascal J. Goldschmidt of Ohio State University in Columbus. They don't always distinguish between a cut finger and an internal blood vessel damaged by heart disease.

As a result, platelets sometimes aggregate at an internal site, clog an artery, and cause a heart attack.

Enter aspirin. Doctors are convinced that the inexpensive drug counteracts platelet aggregation, so roughly 95 percent of people who've had a heart attack take aspirin for years afterward to help maintain blood flow. Yet aspirin prevents heart attacks in only 40 percent of this group, research has shown.

Goldschmidt and his team now suggest that some people who benefit significantly from aspirin have the less common version of a gene called [Pl.sub.A2]. In these people, the drug more effectively keeps platelets from teaming up with a protein called fibrinogen and initiating a cascade of events that leads to clotting, the researchers report in the April 25 Lancet.

Past research has shown that about 25 percent of whites, 15 percent of blacks, and a few percent of Asians have at least one copy of this variation of the [Pl.sub.A2] gene. The gene encodes the platelet receptors that hookup with fibrinogen.

The researchers compared blood samples from 11 people with the genetic variation to samples from 15 people who don't. The groups were otherwise matched by gender, race, and age. The researchers added aspirin and a clot-inducing substance to each blood sample, then gauged the aspirin's anticloting effect. Blood from people carrying the genetic variation needed only one-tenth as much aspirin to inhibit coagulation.

"There is a growing appreciation of the potential limits of aspirin therapy in some patients," says James J. Ferguson, a cardiologist at the Texas Heart Institute in Houston. "This study shows that mechanistically we're beginning to unlock the secrets of aspirin and why some people don't respond to it."

"If we are right," says Goldschmidt, "then genotyping, which might cost $50 as part of a blood test, would be able to help predict which people can be protected by aspirin." People without the variation might be better off taking a different anticoagulant, he says.

Using the test that measures platelet aggregation when blood is exposed to aspirin might also highlight those people who are "nonresponders" to the drug, Ferguson says. While the findings show clear differences, they don't directly address the effects that daily doses of aspirin might have on clotting, cautions co-author Paul F. Bray, a hematologist at Johns Hopkins Medical Institutions in Baltimore.