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Upcoming Study Will Investigate Genetics and Warfarin Dosage

In November 2006, a new federally funded research study will attempt to establish whether genetics can play a decisive role in a patient’s tolerance of warfarin, an oral anticoagulant. The study, funded by the U.S. Food and Drug Administration (FDA), will enroll up to 800 patients being treated with the drug. Warfarin is commonly used to prevent heart attacks, strokes and blood clots, but often causes serious side effects such as prolonged heavy bleeding. Determining optimum dosage with warfarin is a challenge for many doctors who often have to adjust doses in the first phases of therapy, which can sometimes cause complications in patients.

Brian F. Gage, MD, MSc, is Associate Professor of Medicine at the Washington University School of Medicine in St. Louis and Medical Director of the Barnes-Jewish Hospital Blood Thinner Clinic. Dr. Gage, who specializes in anticoagulation and stroke prevention, is leading a pilot study of warfarin-focused genetic testing for the National Institutes of Health. “It’s a very difficult drug,” said Gage. “Each person has a limited range where they have the right thinness of blood. It’s hard to get (it) right the first time.” 

Preliminary genetic screening could help providers pinpoint safe and effective warfarin dosage before initial treatment, thus avoiding the early risks associated with the “trial-and-error” approach.

Prior to treatment, DNA testing conducted by researchers will focus on two genes: CYP2C9 and VKORC1. CYP2C9 is an enzyme-producing gene that helps the body metabolize medicines. Certain variations in it could indicate that a patient will metabolize warfarin more slowly, requiring a smaller dose.  

VKORC1 is the gene that produces vitamin K-dependent clotting factor (II, VII, IX and X), the same blood-clotting protein that warfarin is designed to block. If a patient carries the variation of the gene that produces a smaller amount of the protein, the physician could presumably recommend treatment with smaller amounts of warfarin.

Although pharmacogenetics, genetically based prescribing, is a fairly new and promising science, some factors can contribute to complications while on warfarin therapy. Frequent travel, emotional stress, interaction with other medications, certain foods and taking particular vitamins and herbs can all affect how the human body processes warfarin. 

Source: Associated Press Worldstream, September 4, 2006


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