By Shawna Vogel

B O S T O N, April 20 — A drug used to prevent heart attacks and strokes has been linked to a dangerous and sometimes fatal blood disease, according to a study released early today by the New England Journal of Medicine.
     The drug, Plavix, prevents blood clotting and is used by an estimated 2 million Americans and 3 million heart patients worldwide.
     Today’s article describes 11 patients who, shortly after starting Plavix, developed thrombotic thrombocytopenic purpura, or TTP, a disease in which blood platelets are destroyed. Ten to 20 percent of people who get TTP die from it, even when they are treated promptly.
     “The study alerts us that physicians and patients should be aware of this potentially serious side effect from the drug,” says Dr. Rodman Starke, executive vice president of science and medicine at the American Heart Association.
     Starke, like other physicians, warns that patients should not just stop taking the drug, but should instead consult with their physicians about whether to change medications.
     Sanofi-Synthelabo, the company that manufacturers the drug, and Bristol-Meyers Squibb, which markets the drug in the United States, have agreed to re-label Plavix (tradename clopidogrel), warning patients that TTP is a possible side effect of the medication. Some physicians have also been contacted by these companies about the drug’s effects.

A Friend’s Illness
The lead author of the study, Dr. Charles Bennett, a hematologist at Northwestern University Medical Center in Chicago, began researching Plavix when a family friend nearly died of TTP while taking the drug.
     Because the treatment for TTP is a total exchange of blood plasma, Bennett and his colleagues looked for cases of Plavix-induced TTP by calling blood banks and blood experts as well as the companies that manufacture and market Plavix.
     Between March 1998 and March 2000 the researchers turned up eleven cases of TTP in patients taking Plavix. But they say their search was by no means exhaustive.
     “We suspect once this article is published, many more cases will be forthcoming,” says study coauthor Dr. Marc D. Feldman, at the University of Texas Health Sciences Center in San Antonio.
     “I think it’s very clear that when a report like this comes out the number of cases skyrocket,” says Raymond Woosley, director of the Center for Research and Education on Therapeutics at Georgetown University in Washington, D.C. “People start thinking ‘I’ll go back and look at this case that I saw last month.”

What’s The Risk?
Plavix was widely thought by physicians to be safer for heart patients than an earlier, similar drug called Ticlid (tradename ticlopidine) which typically can cause TTP in one of every 1600 patients treated. While today’s study calls Plavix’s safe reputation into question, it doesn’t say just how great the risk of contracting TTP from it is.
     Feldman, who helped determine the TTP frequency for ticlopidine, says, “We do not know the incidence for Plavix. But we would estimate that it’s similar.”
     Other researchers argue that Plavix is still likely to be much safer than the earlier drug.
     “It looks like the incidence is one hundredth that or less of ticlopidine,” says Dr. Eric Topol, chief of cardiology at the Cleveland Clinic Foundation, figuring that only 11 cases have turned up out of all the people that have used Plavix. “It took 3 million people being treated in practice for this finally to surface. So it seems to be quite rare.”
     Like other physicians, Topol points out that a clinical trial of Plavix in 19,000 closely monitored patients prior to the drug’s approval turned up no cases of TTP.

     ABC NEWS’ Mary Harris contributed to this report.

Advice to Current Plavix Users In light of the potential risk of TTP, doctors say their advice to people using Plavix depends to a great extent on why it’s being used.      Plavix is often prescribed for people who receive stents — tubes made of wire mesh that are placed inside the arteries of the heart to keep blood flowing. The drug is given for only four weeks to help keep clots from forming on the metal.      For such short-term uses, “the risk benefit ratio may clearly lean toward the drug,” says Dr. Peter Libby, chief of the cardiovascular division at Brigham and Women’s Hospital and Mallinckrodt Professor of Medicine at Harvard Medical School in Boston.      However, Feldman says, “We’re recommending shortening therapy from four weeks to two weeks.”      Many people who are at risk for heart attacks also take Plavix for years to reduce their risk. And in those patients, particularly if they’re not allergic to the more common blood thinner, aspirin, doctors say the potential for TTP is something to consider.      “The incremental benefit over aspirin is small,” says Libby. “So for someone who is not allergic to aspirin and where it’s a choice between [Plavix] and aspirin for long-term use then I think they should discuss this with their physician.”      In addition, both physicians and users should be aware of the warning signs of TTP.      “TTP can often masquerade as a stroke,” says Topol. “But there are other things that should arouse suspicion,” he says, including fever, red blood cells that look like they’ve been “cut by a machete,” and profound drops in the number of platelets in the bloodstream.