Stopping platelets at the source

Slowing the production of clot-forming platelets may protect against heart attack and stroke without the risk of excessive bleeding posed by aspirin and other anti-clotting medications, scientists report. The new study, in which an antibody is used to limit the outflow of clot-forming platelets from the bone marrow in baboons, appears in the June 23 Science Translational Medicine.

Preventing blood clots is a delicate business. Clots lodged in arteries are responsible for most strokes and heart attacks, which is why many people take aspirin or prescription drugs — to make platelets less likely to bind to a protein called fibrin and form a clot.

But clotting also serves a life-saving purpose by stanching bleeding from a wound, internal or external. Reducing clotting too zealously places a person at risk of bleeding to death.

In the new study, a team led by biomedical engineer Stephen Hanson of the Oregon Health & Science University in Portland used an experimental antibody-based drug to lower the platelet count in baboons. The drug inhibits a hormone called thrombopoietin, or TPO, which normally would trigger cells in the bone marrow to produce platelets.

The researchers injected some baboons but not others with the antibody drug, then inserted a collagen graft into a blood vessel of each animal, an intervention known to induce clotting. By reducing the number of platelets in the animals but keeping them within the broad range considered normal, the scientists substantially limited clot formation.

In a separate test, baboons received a small cut on the arm. In animals getting the antibody-based platelet blocker, bleeding stopped in 4.3 minutes, as opposed to 3.3 minutes when not getting any drug. But baboons getting aspirin took 6.7 minutes to stop bleeding, compared with 3.4 minutes while not on aspirin.

“These data look pretty good,” says Joseph Italiano, a hematologist at Harvard Medical School. More study is needed to ascertain whether lowering platelet levels in people will improve their chances against heart attack or stroke, he says.

Meanwhile, high platelet concentrations might also be implicated in other diseases, including cancer, he says. “I think the more we understand how platelets play a role in different disease processes, we’re going to want to manipulate their levels. This certainly will be one way to bring them down.”

It could be that people have inherited a strong clotting apparatus that protected us during the rough-and-tumble Stone Age, when trauma and bleeding to death was a more serious threat than having a heart attack, Hanson says. “It’s possible that there simply might be too many platelets” in some people, he says.

A company called BioVascular has already begun testing a pill form of the antibody drug, called BVI-007, in people.