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Researchers Find Better Way to Determine Dose of Anti-Clotting Medicine


Warfarin is a medication used by millions of people around the world. It is also used as rat poison. The medication prevents blood clots in those who form clots easily. These clumps of cells can cause a stroke if they reach the brain, or they can form clots in the lung that can be fatal.

But dosing for the drug is tricky: Give too little and it's not effective; give too much and the patient's blood will be too "thin," and a simple cut can cause excessive bleeding. It's the same property that makes warfarin a good rat poison. Doctors usually have to try different doses to find the correct dose. It's a process that can take weeks and requires many blood samples from patients.

Now an international team of doctors has found a better way to determine the right dose for patients, other than the usual method. Michael Wagner from the University of North Carolina was part of that team.

"With many drugs, people can have a fairly wide range of dosing and still get good effects, and not get the bad effects," Wagner says. "That's not true for warfarin; the range that you have to maintain in your dosing is very narrow, and it differs substantially between different people. People may vary as much as 10-fold in how much warfarin that they need in order to achieve the same level of anti-clotting effect."

In order to come up with the right initial dose, doctors assess standard factors, such as the patient's age, gender and ethnicity. But essentially, Wagner says, they're making a guess. He adds that current decision-making algorithms are useful, but not terribly accurate.

For this research, Wagner and his colleagues pooled data from all over the world about many different ethnicities. They focused in on several genes that are already known to affect how a person responds to warfarin.

"What we're doing was adducing this algorithm or formula that we feel will be more widely applicable in doctors' practices to be able to predict the warfarin dose that you should start a patient out at," he says. "[This] gets them to their final dose more quickly."

And when doctors can add genetic testing into the mix, Wagner says dosing becomes much, much more accurate.

"You get a little swab and scrape the inside of their cheek, and that picks up a few of the cells that are normally being shed off of your mucous membranes... and you send that to a lab," Wagner explains. "DNA is extracted from that, and the specific variants in these two genes can be assayed in the lab, and you can return that results to the doctor and say, 'This patient has the normal form of the gene. This patient has the variant form of the genes.'"

Wagner says that for doctors who don't have genetic testing at their disposal, the researchers refined the questionnaire used to determine the best dose. Their algorithm is even available on a special Web site - warfarindosing.org.

Wagner's research is published in the New England Journal of Medicine.


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