Warfarin sensitivity testing (genotyping) may be used to help determine someone's likely sensitivity or, less commonly, resistance to warfarin and to help select appropriate doses. Warfarin (Coumadin®) is an anticoagulant, a drug that is prescribed to help prevent inappropriate blood clotting (thrombosis and thromboembolism) in people who are at risk, or to help keep an existing blood clotting condition from getting worse.
Warfarin genotyping identifies variations in certain genes.
The VKORC1 gene codes for the protein that warfarin targets. A variation in this gene may result in a protein change that may be more sensitive or less sensitive (or resistant) to the anticoagulant effect of warfarin. Depending on the variant present, the person tested may need a lower or higher initial dose of warfarin.
The CYP2C9 gene codes for a protein involved in the breakdown (metabolism) of warfarin. People with variations in this gene may metabolize warfarin more slowly, resulting in slower clearance of the drug and accumulation in the body over time. They may require a lower dose of the drug.
This testing may sometimes be used to help determine an appropriate dose for a person who has previously taken warfarin and either experienced inappropriate clotting or bleeding episodes while on warfarin or had to go through many dose adjustments to reach a stable anticoagulant ("blood-thinning") effect.
CYP2C9 and VKORC1 genetic testing is not widely used at this time. Although studies have shown that these genes contribute to a person's sensitivity to warfarin and can account for a significant percentage of the person-to-person variation in warfarin doses, there is not a consensus on the need for the testing yet.
Warfarin sensitivity testing may be ordered prior to a person taking warfarin for the first time but may also be ordered when a person has had difficulties with achieving a stable anticoagulant ("blood-thinning") effect or has experienced either excessive blood clotting or bleeding.
Not everyone who is prescribed warfarin will have this test done. At present, there is no consensus on the usefulness of this test and it is not yet widely accepted.
Warfarin sensitivity testing will identify the CYP2C9 and VKORC1 genetic variants (i.e., genotype) present for the person tested. The results must be interpreted carefully to help determine if the person is likely to need a relatively lower or higher dose of warfarin. These results are often interpreted by a specialist.
Those who have one or more variant CYP2C9 or VKORC1 gene copies are more likely to need a lower or higher dose of warfarin. The amount needed will depend on the number and type of genetic variants present but will also greatly depend upon a person's other factors, including health, age, sex, diet, and other medications.
This test detects only the most common genetic variants in CYP2C9 and VKORC1. A person may have a rare variant, resulting in a negative test result, but may still be more sensitive or resistant to warfarin.
Some major health organizations support warfarin sensitivity testing, while others would like to see more data showing that the use of the testing actually has an impact on the health of the patient, such as a decrease in the number of clotting or bleeding events experienced by those on warfarin. Currently, there are studies underway that may provide additional data on health outcomes in the next few years, and that is likely to help determine the clinical usefulness of testing.
The U.S. Food and Drug Administration (FDA) has created changes to the warfarin label to provide information about the usefulness of CYP2C9 and VKORC1 genetic testing and to provide guidance on warfarin doses based upon testing results.
Whatever the initial dosage of warfarin, each person taking warfarin will still need to be monitored with the PT/INR test and all subsequent dose adjustments will be made by taking these test results into account.
Many drugs interact with warfarin and can slow the metabolism of warfarin. Make sure all of your healthcare providers are aware of all the medications you are taking.
Warfarin is prescribed to those at risk for inappropriate clotting, including those who have had a previous blood clot; those with excessive clotting disorders, atrial fibrillation, artificial heart valves; and those who have undergone orthopedic surgeries.
This article was last reviewed on April 2, 2015. | This article was last modified on April 2, 2015.
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