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Warfarin (Coumadin) Sensitivity - Information

Information this test provides.    

People at increased risk of forming blood clots may be prescribed warfarin, which is most commonly marketed under the tradename Coumadin® .  This can prevent serious health problems such as myocaridial infarction (heart attack) and stroke, both of which may be fatal.  While there are well established medical benefits for prescribing warfarin to certain patients, there are also potential adverse reaction to the drug, the most serious being hemorrhage (bleeding) which can be fatal.  It has historically been difficult for physicians to adjust warfarin dosages to maintain efficacy (anti-thrombotic effect) while minimizing side effects (hemorrhage).  Standard practice has been to periodically measure prothrombin clotting times (PT/INR) and adjust the dose of warfarin as needed. 

It is now known that genetic variants in each patient affect the dose of warfarin which will yield optimal medical benefit with reduced risk of side effects for that individual.  Approximately 40-50% of the variability in warfarin response is genetic.  In January, 2010, the U.S. Food and Drug Administration (FDA) updated the warfarin label to provide information on these genetic variants, and to recommend that physicians use a patient's genetic test results to select a starting dose of the drug.  The FDA also provided the expected stable maintenance dose of warfarin for patients, based on their genetic test results.  At this time, the FDA does not require that these genetic tests be performed prior to prescribing warfarin. 

 Warfarin sensitivity- basic panel                           

(not available at this time)

This genetic test determines whether the patients contain genetic variants that are known to increase sensitivity to warfarin.  These individuals may be prescribed lower doses of warfarin that will retain the desired therapeutic effects while minimizing the risk of hemorrhage.  The genetic variants tested for are:

  • CYP2C9  This gene encodes the cytochrome P-450 enzyme in the liver that is principally involved in elimination of warfarin.  The normally functioning gene product is referred to as *1.  Two genetic variants of CYP2C9, referrred to as *2 and *3, metabolize warfarin slower.  In individuals with one or both of these variants, warfarin is degraded slower and remains in their system longer.  Lower doses of warfarin are recommended for these patients. 
  • VKORC1  Warfarin inhibits blood clotting by interfering with the protein expressed by the VKORC1 gene.  Many people have a variation in this gene (-1639  G>A) that reduces the protein function even in the absence of warfarin.  Lower doses of warfarin are recommended for these patients. 

This genetic test will determine whether the patient has one or more of the above genetic variants.  Based on this genotype information, these individuals' physicians can prescribe doses of warfarin that retain clinical benefit while reducing the risk of adverse reactions.  The patient's expected stable maintenance dose, as reported by the FDA on the package insert, is included in the patient's test result report.  

 (not available at this time)

Additional warfarin sensitivity test information:

Additional pharmacogenetic information:

 

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