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Warfarin Sensitivity Testing

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Also known as: Warfarin Sensitivity Genotyping
Formal name: CYP2C9 Genotype; VKORC1 Genotype

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The Test Sample

What is being tested?

Warfarin (Coumadin®) is a "blood-thinner" (anticoagulant), a drug that is commonly prescribed to help prevent inappropriate blood clotting (thrombosis and thromboembolism) in individuals who are at risk or to help keep an existing blood clotting condition from getting worse. Warfarin sensitivity testing helps determine if a person may be more sensitive (i.e., require lower doses) or, less commonly, resistant (i.e., require higher doses) to treatment with warfarin because of his or her genetic makeup. This test detects common genetic variations in two genes, CYP2C9 and VKORC1. A health practitioner may sometimes order this test to help select appropriate doses of warfarin and/or to achieve appropriate dose levels more quickly.

Warfarin can be a challenging drug to administer and monitor because its levels can be affected by many different factors and it has a narrow window in which it is effective. If a person is given too little drug, he or she may be at risk of forming a blood clot; if given too much drug, he or she may be at risk of moderate to severe bleeding episodes. The range between too much drug and too little drug is small and it varies significantly from person to person.

Historically, health practitioners have given warfarin doses based upon age, weight, and sex, and then have monitored and adjusted dosages using frequent PT/INR (prothrombin time/international normalized ratio) tests to determine the medication's anticoagulant ("blood-thinning") effect. Health practitioners then use periodic PT/INR tests to ensure that a stable dose with sufficient anticoagulation has been achieved. Although this dosing strategy is still commonly used, it can take as long as several weeks.

Genetic testing for warfarin sensitivity may help to shorten the time it takes for some people to reach a stable dose; that is, to achieve adequate "blood-thinning" without bleeding episodes. Most often, it is determined that people are more sensitive to warfarin and may need smaller doses; however, there are some people who are less sensitive and may need larger doses. The reason for the relative sensitivity can be, at least in part, due to the individual's genetic makeup and may involve two genes:

  • The VKORC1 gene codes for the production of a protein (VKOR) that is involved in the production of functional forms of certain clotting factors (II, VII, IX, X) that allows them to participate in the clotting process. Warfarin prevents the action of VKOR. Therefore, a variation in VKORC1 may cause someone to be more or less sensitive (or resistant) to warfarin.
  • The CYP2C9 gene codes for the production of a protein (CYP2C9) involved in the breakdown (metabolism) of warfarin. People with CYP2C9 variations may not be able to get the drug out of their system as efficiently as others. The people who clear the drug more slowly may require lower (sometimes significantly lower) doses of warfarin.

Each person receives one copy of each of their genes from their mother and one copy of each of their genes from their father. Thus, each of the CYP2C9 and VKORC1 genes is present in the body as two inherited gene copies (alleles). Any person could have both copies of a gene without any variants (wild-type); one copy without variants and one copy with a variant (heterozygous); both copies with the same variant (homozygous); and both copies with different variants ("compound heterozygous"). The combination of CYP2C9 and VKORC1 gene copies that a person has can determine the overall effect of warfarin and how rapidly it is metabolized and cleared from the body.

Warfarin sensitivity (or warfarin genotype) testing determines whether CYP2C9 and VKORC1 gene variants are present. Careful interpretation of the results can help the health practitioner decide the appropriate doses of warfarin for the person tested.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.