At a Glance
Why Get Tested?
To determine whether you have CYP2C9 and/or VKORC1 genetic variations and are likely to need lower, or less commonly, higher than average doses of the "blood-thinning" drug (anticoagulant) warfarin
When to Get Tested?
A health practitioner might order this test prior to prescribing warfarin for you; a health practitioner may sometimes order it when you are being treated with warfarin and have had bleeding or clotting episodes or dosing difficulties
A blood sample drawn from a vein in your arm
Test Preparation Needed?
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.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Chong, K. (2013 November 11, Updated). Warfarin Dosing and VKORC1/CYP2C9. Medscape Drugs and Diseases Available online at http://emedicine.medscape.com/article/1733331-overview through http://emedicine.medscape.com. Accessed 03/21/15.
(2013 November 19). Genetic data does not improve anticoagulation control with warfarin. National Heart Lung and Blood Institute Press Release Available online at http://www.nhlbi.nih.gov/news/press-releases/2013/genetic-data-does-not-improve-anticoagulation-control-with-warfarin through http://www.nhlbi.nih.gov. Accessed 03/21/15.
(2013 November 19). Genetic testing could improve warfarin dosing. American Heart Association Late-Breaking Clinical Trial Report LBCT 5/Abstract: 19658 (Hall E). American Heart Association. Available online at http://newsroom.heart.org/news/genetic-testing-could-improve-warfarin-dosing through http://newsroom.heart.org. Accessed 03/21/15.
Heikal, N. et. al. (2014 June, Updated). Warfarin Sensitivity. ARUP Consult. Available online at http://www.arupconsult.com/Topics/WarfarinSensitivity.html?client_ID=LTD through http://www.arupconsult.com. Accessed 03/21/15.
(2014 May).Warfarin Sensitivity (CYP2C9 and VKORC1) 3 Mutations. ARUP Laboratories. Available online at http://ltd.aruplab.com/Tests/Pdf/197 through http://ltd.aruplab.com. Accessed 03/21/15.
Hamberg, A. and Wadelius, M. (2014). Pharmacogenetics-Based Warfarin Dosing in Children. Medscape News and Perspective from Pharmacogenomics. 2014;15(3):361-374. Available online at http://www.medscape.com/viewarticle/821224 through http://www.medscape.com. Accessed 03/21/15.
Sources Used in Previous Reviews
Linnea M. Baudhuin, Ph.D., DABMG, Assistant Professor of Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Shah, S. and Voora, D. (Updated 2010 April 8). Warfarin Dosing and VKORC1/CYP2C9. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1733331-overview through http://emedicine.medscape.com. Accessed May 2011.
Epstein, R. et. al. (2010 March 30). Warfarin Genotyping Reduces Hospitalization Rates Results From the MM-WES (Medco-Mayo Warfarin Effectiveness Study). J Am Coll Cardiol, 2010; 55:2804-2812 [On-line information]. Available online at http://content.onlinejacc.org/cgi/content/full/j.jacc.2010.03.009v1 through http://content.onlinejacc.org. Accessed May 2011.
Moyer, T. (2009 December). Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience. Mayo Clinic Proceedings v 84 (12) 1079-1094 [On-line information]. Available online at http://www.mayoclinicproceedings.com/content/84/12/1079.full through http://www.mayoclinicproceedings.com. Accessed May 2011.
Mehra, M. (2010 March 16). MM-WES: Genetic testing for warfarin sensitivity linked with reduction in hospitalizations By American College of Cardiology 59th Annual Scientific Sessions. Cardiologytoday [On-line information]. Available online at http://www.cardiologytoday.com/view.aspx?rID=62016 through http://www.cardiologytoday.com. Accessed May 2011.
Bell, J. (2008 October). Experts Debate Pharmacogenetic Testing for Warfarin Sensitivity. Tests Could Enable Better Dosing, But Some Question the Data. AACC 2008 Annual Meeting Highlights, Clinical Laboratory News v 34 (10) [On-line information]. Available online at https://www.aacc.org/publications/cln/2008/october/Pages/am08_highlights1.aspx through https://www.aacc.org. Accessed May 2011.
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Check, W. (2009 January). PGx tests for warfarin dosing—how soon? CAP Today [On-line information]. Available online through http://www.cap.org. Accessed May 2011.
Karp, J. (2010 March 1). SNP Testing for Warfarin Sensitivity. College of American Pathologists NewsPath [On-line information]. Available online through http://www.cap.org. Accessed May 2011.
Krautscheid, Patti et. al. (Updated 2010 June). Warfarin Sensitivity. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/WarfarinSensitivity.html?client_ID=LTD through http://www.arupconsult.com. Accessed May 2011.
Verhoef; T. et. al. (2010 September 17). Clinical and Economic Consequences of Pharmacogenetic-guided Dosing of Warfarin. Medscape Today from Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(4):375-378. [On-line information]. Available online at http://www.medscape.com/viewarticle/727897 through http://www.medscape.com. Accessed May 2011.
Nainggolan, L. (2009 February 19). Prediction of Initial Dose of Warfarin Aided by Genetic Testing. Medscape News Today from Heartwire [On-line information]. Available online at http://www.medscape.com/viewarticle/588489 through http://www.medscape.com. Accessed May 2011.
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(Updated 2011 May 13) Frequently Asked Questions About Pharmacogenomics. National Human Genome Research Institute [On-line information]. Available online at http://www.genome.gov/27530645 through http://www.genome.gov. Accessed May 2011.
Carlson, E. (2009 February 25). Web Exclusives: Genetics, Math Gives Blood. National Institute of General Medical Sciences [On-line information]. Available online at http://publications.nigms.nih.gov/computinglife/mathblood.htm through http://publications.nigms.nih.gov. Accessed May 2011.
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Bussey H, et al. Genetic Testing for Warfarin (Coumadin) Dosing? - Not Yet Ready for Prime Time. July, 2007 from Clot Care Online Resource. Available online at http://www.clotcare.com/warfaringenetictesting.aspx through http://www.clotcare.com. Accessed October 2011.
Sconce E, et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood. October 1, 2005 vol. 106 no. 7 2329-2333. Available online at http://bloodjournal.hematologylibrary.org/content/106/7/2329.full through http://bloodjournal.hematologylibrary.org. Accessed October 2011.