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Large Joints Feature

Source: Wikimedia Commons and Hwaja Götz

Customized Coumadin via Genetic Testing

Elizabeth Hofheinz, M.P.H., M.Ed. • Thu, September 28th, 2017

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Dosing with warfarin (Coumadin) is not always clear. A new study, however, has found that genetic testing can help determine the safest dose of the blood thinner warfarin, with fewer side effects, in patients undergoing joint replacement surgery.

Their work, “Genetics Informatics Trial (GIFT) of Warfarin to Prevent Deep Venous Thrombosis: Benefit of Pharmacogenetic Dosing,” appears in the September 26, 2017 edition of the Journal of the American Medical Association.

"Warfarin is very effective in preventing blood clots, but it's very difficult to regulate," explains Anne R. Bass, M.D., a rheumatologist at Hospital for Special Surgery (HSS) in New York City and study co-author, in the September 26, 2017 news release. "About half of the population, because of genetic variants, is very sensitive to warfarin or has a very unpredictable or delayed response to the drug. This is the first study to show that adjusting the dose based on these genetic variants makes warfarin safer for patients."

As written in the news release, “The multicenter clinical trial, known as GIFT (The Genetic Informatics Trial of Warfarin to Prevent Deep Venous Thrombosis) was funded by the National Institutes of Health [NIH]. Brian F. Gage, M.D., professor of Medicine at Washington University, served as principal investigator. Hospital for Special Surgery had the highest number of study participants—almost 1,000 joint replacement patients.”

“Investigators collected data on a total of 1,600 individuals age 65 and older undergoing hip or knee replacement surgery. Patients were randomly assigned to one of two groups. One group received warfarin dosing based on clinical factors known to affect warfarin dose such as age, height and weight, gender, race, and other medications; the second group's dose was based on these factors plus genetic variants. The study zeroed in on genetic variants in three genes, and this genetic information helped guide warfarin dosing during the first 11 days of treatment.”

Asked about adjusting the dose based on genetic variants, Dr. Bass told OTW, “Adjusting the warfarin dose without genetic variants and without a computer dosing algorithm can be tricky because different people respond to the warfarin differently, some are very sensitive and somewhat resistant. By using a dosing algorithm that can incorporate genetic variants dosing is made much less tricky.”

Regarding insurance coverage, Dr. Gage commented to OTW, “Currently, most insurance companies choose not to cover the cost of genetic testing. However, that decision could change if the Centers for Medicare and Medicaid Services (CMS) choose to cover the cost of genotyping for Medicare beneficiaries.”

“First, pharmacogenetic dosing improves the safety of warfarin thromboprophylaxis among elderly patients undergoing hip or knee arthroplasty. Second, warfarin dosing algorithms are readily available through an NIH-supported non-profit website,,

but they require INR [international normalized ratio] monitoring (e.g., twice per week for the first couple weeks). Third, one month of warfarin prophylaxis with a target INR of either 1.8 or 2.5 was safe—no GIFT participant died, and most were discharged home on post-op day 1 or 2.”

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