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Ask Dr. Stephan Moll
These questions have been submitted by folks on the mailing list and answered by Dr. Moll, Director of the Thrombophilia Program at the Carolina Cardiovascular Biology Center, Department of Medicine, Division of Hematology-Oncology, UNC Chapel Hill (North Carolina, USA). Why am I doing this?
28. Coumadin resistance
Last Updated: 1/31/2008
Q: "Is there something like Coumadin®
resistance, and if so, what are the treatment alternatives? The reason I
am asking is that I have seen a few members mentioning that they are on
20 mg of Coumadin, and still they cannot get their INR to go up."
A: Yes, warfarin (coumadin®) resistance exists.
It is rare. Possible causes are:
- interactions with other medications (that decrease the INR);
- extreme diets with large amounts of vitamin K;
- malabsorption, leading to lack of absorption of warfarin (in patients with gastrointestinal disease);
- non-compliance with taking warfarin;
- inherited metabolic reasons
The term “Warfarin resistance” is
used when patients require high doses of warfarin (such as more than 20
mg per day) to get their INR (International Normalized Ratio) into the therapeutic
range. What should one do if the INR just does not increase sufficiently
in spite of increasing the dose of warfarin? Just increase the warfarin
dose further, until a therapeutic INR is reached. I would not have a problem
recommending doses of 30 or 40 mg a day. If one still does not get a therapeutic
INR, one can consider choosing a low molecular weight heparin or Fondaparinux
for long-term anticoagulation.
Reference:
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As for the inherited reasons: Several recent reports have elucidated
genetic mutations that lead to high warfarin requirements, i.e. warfarin
resistance (references 1-3). These mutations are in the gene called VKORC1,
which renders the enzyme “vitamin K epoxide reductase” (the
therapeutic site of warfarin) resistant to warfarin.
Reference:
- Rost S et al. Nature 2004;427:537-541.
- Bodin L et al. J Thromb Haemost 2005;3:1533-1535.
- Loebstein R et al. Blood 2007;109:2477-2480.
Disclaimer
The information contained on the this web site is provided for your general information only. I am not a doctor and I do not give medical advice or engage in the practice of medicine. I do not recommend any particular treatment/trial for individuals, and in all cases recommend that you consult your physician or local treatment center before pursuing any course of treatment. It is up to you, as a consumer to find out if these trials posted are something you want to participate in. I just post the information.
The information contained on the this web site is provided for your general information only. I am not a doctor and I do not give medical advice or engage in the practice of medicine. I do not recommend any particular treatment/trial for individuals, and in all cases recommend that you consult your physician or local treatment center before pursuing any course of treatment. It is up to you, as a consumer to find out if these trials posted are something you want to participate in. I just post the information.