Genetic variation affects anti-clotting drug

[LUVMyBirman]

Jun 03 (HeartCenterOnline) - Researchers may have discovered a genetic variation that would help explain why warfarin, a popular anticoagulant, can be a difficult drug to prescribe.

It is estimated that about 2 million Americans are given warfarin on any given day. The drug is a powerful anticoagulant, used to prevent blood clots and reduce the chance of a stroke or heart attack.

However, warfarin is unpredictable among different patients. Some patients need higher doses, while other patients require less. Too much warfarin may result in increased risk of bleeding, while too little may increase the odds of a blood clot forming.

In a study published in the June 2 edition of the New England Journal of Medicine, researchers from the University of Washington in Seattle and Washington University in St. Louis, looked at the genes that control blood clotting.

One gene in particular, called vitamin K epoxide reductase (VKORC1), accounted for about 25 percent of the variability in the drug among different patients.

Based on these results, researchers were able to group patients in three categories -- high dose, intermediate dose and low dose -- depending on which variations they had in VKORC1.

Although genetic testing is not routinely part of warfarin dosing, this study may help physicians give more precise doses, more quickly, than the current method of trial and error. In some cases, it may take months of clinic visits and multiple needle sticks to arrive at the right dosage.

Copyright 2000-2005 (HealthCentersOnline)

To read related news stories, click on any of the following:
Aspirin superior for preventing stroke
Study supports controversial blood-thinning drug
Gene discovery may shed light on blood-clotting
Study shows success with new anti-clotting drug

For additional information, visit HeartCenterOnline's:
Blood Clot Center
Cholesterol Center


Publish Date: June 03, 2005

 

[Ross]

Interesting, but why do I feel like the study is a waste of time? 25% is an awful low number to be basing much of anything on. Not trying to shoot your post down. It just sounds as though their wasting time and resources following shadows.

 

[LUVMyBirman]

Interesting, but why do I feel like the study is a waste of time? 25% is an awful low number to be basing much of anything on. Not trying to shoot your post down. It just sounds as though their wasting time and resources following shadows.

Keeps them employed I suspect Thought it was kind of interesting. If it works......it may save a lot a hassle when a patient begins treatment.

 

[Guest]

Barry also started a post about this last week. I thought that I had replied, but I guess not since nobody did.

There have been a number of studies lately showing different starting doses by ethnicity and genetic variations. If any of you were awake during my talk at the reunion in October, you may recall that I talked about some of this.

I recently took some graph paper and superimposed the studies on one another. Guess what? The studies showed an overlap of what I have been doing for the past 8 years. If the person is under 65 years old I give them 5 mg per day to start. If the person is over 65 years old I give them 4 mg per day. I will make a 1 mg per day up or down adjustment if the person is very frail, immobile, or very large or extremely active. I think that I get them in range just about as quickly as doing the more expensive genetic testing.

When you couple the cheapness of my method with the small risk of an adverse event on any one given day, I think my method is extermely cost-effective. Still it is nice to know that there is some science behind my method even if I didn't know it.

 

[Barry]

...more expensive genetic testing....

From what I heard on NPR, the point wasn't to try to come up with a cost-effective method for determination of Warfarin dosage in clinical practice - it was more pure science than applied science. They wanted to check into genetic testing to determine medication dosage, and ended up using Warfarin as the drug to look at in the initial study because it's a well-researched drug and because so many folks are on it it would be easy to come up with subjects for the study. I doubt that it would ever prove to be cost-effective in clinical practice with Warfarin because there are so many other variables that determine appropriate dosage - diet being the one that gets discussed here the most.

 

[Guest]

Diet gets discussed the most and in reality probably means the least.

Every time someone's INR is low, they want to blame it on eating more salads. But experience has shown that if you adjust the dose it the INR is almost always high at the next session because they have gone back to their old eating habits.

So I pretty much ignore dietary changes unless they are out of range for two or three visits.

 

[Guest]

I know several of the people doing these studies. They are not pure scientists. They are trying to find cost-effective ways to treat people.

There was another study published today about the average doses. Men under 50 required an average of 6 mg per day and women over 80 required an average of 3 mg/day. Again very little variation from my 4 mg for people under 65 and 5 mg for people over 65. Then go up or down 1 mg for extreme cases.

Most hematologists are more interested in the cancer portion of the field rather than purely experts on blood. Then take the ones who are interested in warfarin research and you have a really small group. I have met and talked with most of them. One month ago I had dinner at at a table for six and one of those people was Elaine Hylek, one of the co-authors of today's article.

 

[Barry]

Diet gets discussed the most and in reality probably means the least...

I don't know that I understand:

Variation in diet doesn't affect one's INR that much?

Or don't worry about your diet, eat what you eat and adjust the Warfarin dose to that?

Or...?

 

[Guest]

You gotta be really goofy about your diet to have it affect the INR. I had a lady eat a whole bag of cole slaw mix by herself in two days. Two days after that I checked her INR. It was 1.7 (range 2 - 3). I asked her if she was going to continue this and she said, "Ach, NO, I'm German and I chust had a taste for cabbage." So I have concluded that if a pound of cabbage over two days only lowered her INR to 1.7 there can't be much to this food affecting warfarin stuff.

Over about 30,000 patient visits, I have found this to be true. It appears that the average time that a person sticks to a more healthy diet is well short of one month. So if I increase someone's warfarin dose because they say they have switched to a more healthy diet what happens is their INR is too high the next month because they have already reverted back to the old eating habits. So now I ignore "healthy diets" until the can show that their INR is low for two or three months consecutively. I have found that it is a lot easier to manage the warfarin doing this because (evidently) few people stick to a diet for very long - myself included as those of you who have eaten with me will probably attest.

So I think that food is the most overrated reason for the INR being out of line.