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New blood thinner studied for patients with leg and lung clots

February 13, 2007

A new oral blood thinner is being compared to an old standby to see if it works as well and is easier to manage long term, researchers say.

Other medications and even diet can dramatically impact blood levels of warfarin, or Coumadin™, increasing the risk of bleeding or clotting, says Dr. James R. Gossage Jr., pulmonologist at the Medical College of Georgia.

"You eat too much broccoli or spinach and it sends your levels out of whack; almost every other medicine affects Coumadin," says Dr. Gossage, who calls warfarin a "high-maintenance" medication.

Unfortunately, many people, including those with a clot in their legs - called deep vein thrombosis - or their lungs - called pulmonary embolism - may need it for months or years, Dr. Gossage says.

An international study of 2,000 adult patients with these problems will determine if dabigatran, manufactured by Boehringer Ingelheim, a Germany based pharmaceutical company, makes long-term clot control easier.

Deep vein thrombosis or a pulmonary embolism generally are treated with intravenous blood thinners; really big clots also may need a clot-buster like tPA, says Dr. Gossage, a principal investigator on the study. Blood thinners keep the clot from growing while the body's endogenous clot-busters eliminate it. That can take a while, especially when clots measure several inches or more, so patients also need a blood thinner they can take at home for months or longer, depending on their diagnosis. When patients start taking warfarin, they need daily, then weekly monitoring until levels stabilize, then at least monthly checks as long as they take the drug, he says.

At the right level, the drug works well, inhibiting vitamin K, which is involved in the synthesis of several coagulation factors and found in abundance in green leafy vegetables, vegetable oils, cranberries and even licorice. "It's very uncommon for a person taking warfarin to have a blood clot if his or her level is in the proper range," Dr. Gossage says.

The trouble is that a big helping of collard greens, for example, can dramatically reduce the drug's effectiveness and increase clotting risk. Patients are encouraged to eat stable diets, but even so, Dr. Gossage has patients whose blood levels, charted on a graph, look like a roller coaster.

Many common over-the-counter and prescription drugs contribute to the problem by affecting the liver mechanism that determines how much and how fast warfarin is eliminated, Dr. Gossage says. "We are looking for medicines that are more like most others we take; they are not affected by our diet and by every other pill we take," he says.

Previous work with dabigatran indicates it could fit the bill. It works early in the clotting process, inhibiting thrombin, one of the main clotting factors. "When you cut yourself, platelets start sticking, thrombin comes in and activates the whole cascade of coagulation factors that form a clot. Warfarin works later in the cascade, so getting something that works earlier may be even better," says Dr. Gossage.

"Hopefully we won't have these big swings in the level and people won't have these periods where they are at great risk," says Dr. Gossage. "I can give you a dose and it's going to work the same way whether you are eating broccoli or spinach or taking penicillin or some other antibiotic"

This phase III study randomizes patients to warfarin or dabigatran and closely follows them for 18 months. If dabigatran appears ineffective, patients are moved to more standard therapy. All blood thinners can have the side effect of bleeding, he notes.

Immobility, blood vessel injury and anything that increases blood's tendency to clot, called hypercoagulability, are risk factors for clots. "Most people think you have to have at least two of those, says Dr. Gossage.

Long plane rides or hospital stays can put patients at risk ; trauma, even an intravenous line needed for medicine, can injure vessels. A host of things contribute to hypercoagulability, including birth control pills, hormone replacement therapy, age, and perhaps smoking and obesity. Cancer, particularly solid tumors, is a big risk factor for clotting. Ironically its primary treatments, chemotherapy and radiation therapy, can narrow blood vessels and add to the risk.

An estimated 600,000 pulmonary embolisms occur each year in the United States and deep vein thrombosis is about twice as common. Many patients have both because a clot in the leg has nearly a straight shot to the lungs through the venous system.

Medical College of Georgia