Warfarin Dosing and Personalized Medicine
Posted September 17, 2007 by Dr. T.R. Morris
Right out of medical school, while I was studying for my board exams, I took a job at a hospital laboratory in the Ballard district of Seattle. After proving myself by getting blood out of the needle addicts on the top floor I was shipped down to the outpatient lab. During the day the waiting room was often overflowing with clients waiting for blood draws. On average, I’d say that nearly half of the patients were on warfarin and having their prothrombin times tested on a monthly basis. Most of them were not happy campers. For a warfarin patient, bumping your shin on a coffee table can be a major event, so a blood draw is the last thing you want to do. After the blood draws, we had to wrap the patients up very carefully lest they run the risk of returning five minutes later with blood running down their arms from the tiny venapuncture holes.
Why are we testing these patients so often? Warfarin has a very narrow therapeutic window—too much leaves the patient at risk for bleeding, too little leaves them at risk for a heart attack or stroke. That bad situation gets worse when you consider the fact that there is a 10-fold inter-patient variability in the dosing required to attain a therapeutic response in terms of the INR range (International Normalized Ratio target is 2.0-3.0).
Despite all the extra monitoring, warfarin is still the second most common drug (after insulin) implicated in ER visits for adverse drug events. Major bleeding events occur in half of patients during the first 90 days of warfarin treatment. Clinicians and patients alike have been asking for a long time “what can we do about this?”
Before genetic tests were available, clinicians were essentially shooting in the dark with regard to the starting dose for warfarin patients. Recent developments in genetic testing have identified variants in two key genes related to warfarin metabolism: CYP2C9 and VKORC1. Though far from the whole story (depending on who you ask, estimates of the effect of these two genes on warfarin dose variation range from 39-56%) together identifying these two genes holds significant promise in helping health care providers dial in the right dose for patients starting warfarin therapy.
In August 2007, the FDA recommended genetic testing prior to initiating warfarin therapy. The Iverson Warfarin Dosing Panel satisfies this recommendation. Check out the FDA press release here.
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