Warfarin Institute of America
Dedicated To Your Health
THE THYROID THEORY OF WHY WARFARIN (Coumadin, Jantoven) IS HARD TO MANAGE
Many people who are very conscientious about taking their warfarin (Coumadin, Jantoven) experience unexpected, wide variations in their INR. Despite much soul searching, quite often the underlying cause is never discerned. Therefore, I have concluded that the precipitating factor must be something very subtle, and probably exerts an effect long after the event takes place. I have developed a theory about how the thyroid may be the culprit in these swings.
The thyroid is involved in metabolism of vitamin K dependent clotting factors. Warfarin (Coumadin, Jantoven) works by slowing the production of these clotting factors. These two factors appear to be in a very delicate balance.
If you do something to reduce thyroid activity, then you reduce the metabolism of the clotting factors. If you are taking warfarin (Coumadin, Jantoven) and reduce the thyroid activity then there are more clotting factors present. This will cause the INR to decrease.
If you do something to increase thyroid activity, then you increase the metabolism of the clotting factors. If you are taking warfarin (Coumadin, Jantoven) and increase the thyroid activity then there are less clotting factors present. This will cause the INR to increase.
It has long been known that a single dose of potassium iodide will exert its maximum effect on the thyroid after about ten days. Presumably it will take another ten days for the effect to wear off. It may be shorter but it may also be a great deal longer. One of the reasons that it takes up to six months for the effect of amiodarone or warfarin (Coumadin, Jantoven) to wear off may be that the amiodarone has loaded the thyroid with iodine.
Obviously, the simplest method of changing the activity of the thyroid is to change the dose of thyroid medications such as levothyroxine, methimazole or propylthiouracil.
There are other drugs that affect the thyroid either directly or indirectly. Raloxifene, when taken at the same time as levothyroxine can inhibit the absorption of the levothyroxine and by implication could have an effect on the INR.
Iodine is present in most vitamin and mineral supplements. Changing formulations by manufacturers, forgetting a few doses, running out of the vitamin and minerals all may have an effect on the INR.
Iron is another popular ingredient in vitamin and mineral supplements. An iron product taken at the same time as a thyroid tablet can inhibit the absorption of the thyroid medication.
Sucralfate and antacids containing aluminum taken within an hour before or after a thyroid medication can stop absorption of the thyroid.
X-Ray tests that use a contrast dye are well-known to interfere with thyroid function tests possibly for months after their use.
However, there are many, much more subtle ways, that the thyroid can be affected.
Dietary intake of iodine varies greatly throughout the world. Over the past hundred years most of the salt used in food in America has iodine added. But people in America who avoid dairy products, seafood, processed food and iodized salt can become deficient. Conversely, iodine deficiency is a serious problem among the poorest people in India where the ground used to grow food crops has been depleted of its iodine. Iodine depletion can even vary by regions in the same country. For example, in the United Kingdom iodine is depleted from the soil in Derbyshire, the Midlands and the Southwest. Furthermore the natural iodine in drinking water is generally less, the further one goes upland from the ocean. For the poor of India, it is probably fairly predictable that their food was grown nearby. However, in the highly developed areas of the world it is unlikely that the grocery shopper pays little more than a glance at the country of origin of the food being purchased.
What foods are high in iodine? Shellfish (think shrimp) are one of the first to come to mind. Is there a difference in iodine content between those caught in the open ocean and those that are farmed? Saltwater fish (think tuna) may vary in iodine content between fresh-caught and grilled as compared to canned. Other saltwater fish include sea bass, haddock and cod. Kelp (think sushi wrapper), asparagus, garlic, lima beans, mushrooms, sesame seeds (oil?), soy products and spinach are high in iodine. Dairy products from cattle fed grain grown in iodine-rich soil can be high in iodine.
We know that warfarin (Coumadin, Jantoven) dosage adjustments of only 10% to 15% can cause a significant change in the INR. It is also known that people can have large excesses or deficiencies in thyroid hormones before any disease process is evident on physical examination. In Japan, many people routinely ingest 25 to 40 times the daily recommendation of iodine with showing signs of disease. Is is possible that these small, almost undetectable changes in thyroid function are in actuality causing fluctuations in the INR?
Suppose that your INR has been consistently in the therapeutic range. Then you do one of the above activities that throws off your INR. Suppose you go and have your INR checked two weeks after the event. The INR is off so the warfarin (Coumadin, Jantoven) dose is adjusted. Then a month later you have returned to the activity that was keeping the INR in range and you have the INR checked again. This time the INR is off in the opposite direction. You have now entered the roller-coaster INR zone where INR seems to stand for "It's Never Right."
Is this theory correct? I have no idea whether any of this can be proven. I do know that I have seen in excess of 20,000 patient visits where people were taking warfarin (Coumadin, Jantoven). Some of these people have come to my clinic for almost seven years and I have gotten to know them quite well. I believe them when they say that they have absolutely no memory of anything that could have affected their INR. Therefore, I have pondered over what subtle change could these people be making that will affect their INR but that has not been considered important.
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Last updated January 1, 2006