Genetics influence patients' responses to warfarin and can help determine optimal dose

An FDA-approved updated labeling for warfarin to explain the role of genetics in treatment response.

Genetic testing can help personalize the therapeutic dosage of warfarin to administer to patients undergoing total hip or knee arthroplasty, according to a study in the journal Blood.

The finding represents one of the first applications for using patients' genetic information to guide their medical care, according to a press release from the American Society of Hematology.

Currently, physicians estimate the initial dose of warfarin to administer and then continually monitor a patient's International Normalized Ratio (INR) value during treatment, adjusting the dose as needed.

Eric A. Millican, ME, and colleagues at Washington University in St Louis, investigated combining the standard INR method with genetic testing for predicting the therapeutic warfarin dose. The study involved 92 patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (THR) at the Washington University Medical Center.

No patients had previously received the drug, the study authors noted.

Genetic variations

The researchers used blood tests to examine variations in two genes that may affect warfarin dosing — CYP2C9 and VKORC1. Variants in CYP2C9 impair the body's breakdown of warfarin, which variants in VKORC1 cause increased warfarin sensitivity, according to the release.

The researchers found that these two genes were important in predicting the response to warfarin. Also, by combining variants in the genes with initial INR response, and other clinical factors, they derived a dosing equation that estimated the therapeutic warfarin dose to use.

Additional factors, such as intraoperative blood loss and smoking status, also correlated with the appropriate therapeutic dose, according to the release.

The researchers are now validating the model in orthopedic and nonorthopedic patients beginning warfarin therapy, the release said.

The study was funded by the National Institutes of Health.

Labeling revision

Due to the increasing evidence that genetic factors affect patients' responses to warfarin, the FDA recently approved updated labeling for the drug to explain the role of genetics.

The labeling change highlights the opportunity for health care providers to use genetic tests to improve their initial estimate of a reasonable warfarin dose, according to an FDA press release.

Such testing may help optimize use of the drug and lower the risk of bleeding complications, the release said.

For more information:
Millican EA, Lenzini PA, Milligan PE, et al. Genetic-based dosing in orthopedic patients beginning warfarin therapy. Blood. 2007;110:1511-1515.
The dosing model is publicly available at www.warfarindosing.org.