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Warfarin Pharmacogenetics in Clinical Practice?

One-third of patients receiving warfarin metabolize it differently and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The FDA has suggested that these markers should be used to determine the minimal starting dose of Coumadin (warfarin); because patients with variations in these markers may require a smaller dose of Coumadin than those with the normal marker.

“Should We Be Applying Warfarin Pharmacogenetics to Clinical Practice? No, Not Now” is an article Michael H. Rosove, MD, and Wayne W. Grody, MD, PhD published in the Annals of Internal Medicine (subscription needed). What I would like to highlight is the list of key points.

Certain single-nucleotide polymorphisms of the cytochrome P450 CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes influence warfarin metabolism and sensitivity.

The U.S. Food and Drug Administration has modified warfarin labeling to suggest, but not mandate, consideration of pharmacogenetic testing of these genes; the test is now commercially available.

Testing predicts only about one third of all dosing variations.

The value and cost-effectiveness of genetic testing to reduce bleeding or thrombosis rates remain unknown.

Consideration of clinical factors that influence dosing, conscientious prothrombin time monitoring, and sage dosage adjustment remain extremely important in warfarin management.

Further study is required before routine warfarin pharmacogenetic testing can be recommended.

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4 Comments Post a comment
  1. Martin #

    Well, I think this is just not the right case for a rather expensive method like genetic testing: you can easily monitor warfarin effects and it certainly much. much cheaper to do a more intensive monitoring at the first days of treatment than to do an expensive genetic test. Starting a warfarin treament is not done very often in a patients lifetime, so it just cannot pay off.
    I’m curious to see genetic testing in psyiatric pharmacotherapy: I think a lot of suffering (and money) could be saved with a test for the right antidepressant/antipsychotic…

    August 20, 2009
  2. Berci,
    The price point for this test in all estimates is WAY TOO HIGH. Therefore the assumptions are wrong. At 100 USD for both genes this becomes a no brainer for anyone starting warfarin

    August 20, 2009

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