Genetic Testing Determines Safest Dose of Blood Thinner

Warfarin, commonly known as Coumadin, is frequently used to prevent a life-threatening blood clot. It is often prescribed to people having hip or knee replacement surgery, as well as to individuals with certain heart conditions that leave them vulnerable to a stroke.

Warfarin affects people differently, and genetics come into play. Too much warfarin can cause internal bleeding, while an inadequate dose fails to prevent blood clots. Over the last 10 years, warfarin has led to more medication-related emergency room visits among older adults than any other drug. Genetic testing can help determine the safest dose of the blood thinner warfarin, with fewer side effects, in patients undergoing joint replacement surgery.

A team of medical scientists collaborating with those at the Hospital for Special Surgery (New York, NY, USA) 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.

Patients were genotyped for the following polymorphisms: Vitamin K Epoxide Reductase Complex Subunit 1(VKORC1-1639G>A), cytochrome P450 family 2 subfamily C member 9 (CYP2C9*2), CYP2C9*3, and Cytochrome P450 Family 4 Subfamily F Member 2 (CYP4F2 V433M). Patients were monitored for bleeding, blood clots and warfarin overdose and 15% of the patients who were given warfarin in the traditional manner experienced at least one adverse effect, compared to only 11% patients whose warfarin dosing was guided by genetic testing, a statistically significant difference.

Anne R. Bass, MD, a rheumatologist and co-author of the study said, “Warfarin is very effective in preventing blood clots, but it's very difficult to regulate. 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. This was really a study addressing warfarin management and warfarin safety, so I think you can extrapolate the results to other patients taking this blood thinner, such as those with atrial fibrillation.” The study was published on September 26, 2017, in the Journal of the American Medical Association.

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