How is Warfarin Metabolized?

[ALCapshaw2]

I'm confused...

and I think I'm beginning to see some contradictions in our "rules of thumb" about how coumadin acts in our bodies.

We have "Fast Metabolizers" who typically take High Doses of Coumadin / Warfarin (say over 50 mg/week). When they SKIP a Dose, their INR is reported to "Drop like a Rock".

We have "Slow Metabolizers" who typically take Low Doses of Coumadin / Warfarin (say 21 to 28 mg/week which is 3 or 4 mg/day). When they SKIP a Dose, their INR is reported to drop more slowly, maybe about half as fast as for Fast Metabolizers.

One of our "Rules of Thumb" is that it takes 3 or 4 days for Warfarin to be fully metabolized. Wouldn't this number vary between Slow Metabolizers and Fast Metabolizers?

There seems to be some confusion about HOW / How Fast Coumadin is Metabolized over those "4 days". Is it LINEAR, i.e. 25% on day 1, 50% by day 2, 75% by day 3, and 100% by day 4?

OR, is it 0% on day 1, 0% on day 2, 0% on day 3, and 100% by day 4 as some seem to imply? I have a Hard Time accepting this theory.

NOTE that by the theory of Linear Metabolization, the concept of using Loading Doses to bring INR up Faster would seem to be supported, acknowledging that there is the then the issue of OVERSHOOTING to deal with a few days later.

Is there a model that can be applied generally to all patients (i.e. does everyone metabolized linearly, or in some defined non-linear manner)?

IF metabolization is NON-Linear, is there a Single (mathematically defined) Model for this pattern or is it different for everybody?

I've pretty well accepted the notion that there is a variation in SPEED of metabolization between patients.

'AL Capshaw'

 

[geebee]

Huh??????

Actually, for me, I see a change within a couple days when I make adjustments and I take 28mg/week.

 

[Ross]

Oh lord, Al's got his thinking cap on again. Look out world.

I differ this one to the Coumadin Yoda.

 

[ctyguy]

This is an interesting topic for me because Im having challenges getting my INR into proper range for about the last month. I have a Coumadin Clinic managing my INR, checking it currently every two weeks.

8 weeks ago my INR was 1.7, as a result my dose was bumped from 30mg per week to 36mg
6 weeks ago my INR was 1.8, as a result my dose was bumped from 36mg per week to 42mg
4 weeks ago my INR was 2.6, as a result, no change still 42mg per week
2 weeks ago my INR was 3.2, as a result I was instructed to cut my dose for that night to 4mg and to stay at 42mg
Yesterday my INR was 3.6, as a result I was instructed to take 2mg last night and 4mg on Wed, all other days continue with 6mg. Next week I take 6mg every day except Wed, which will be 4mg. So net effect is 42mg down to 40mg.

I am happiest when my INR is between 2.0 and 2.5 so Im questioning if a 2mg reduction is enough, I thought at least 4mg.

Thoughts ?

 

[Nancy]

I will let the engineers speak with you in engineer-speak. Here's what I have observed from Joe having about a million INR tests, some every day while in the hospital, and out of it too. Joe did not want to self-monitor, so perhaps this would make a case for more professional numbers (and maybe not!).

I believe that Coumadin is metabolized in the liver. So liver function is very important for tip-top Coumadin managing.

1.) When Joe was in CHF with ascities involvement, his INR became difficult to manage, His ascites incorporated liver involvement, spleen too (don't know what role the spleen has in INR).

2.) When his kidneys started to become compromised, his INR became difficult to manage.

3.) Diuresis to get rid of the CHF caused his INR to become difficult to manage.

4.) Eating normal greens didn't have much effect.

5.) His INR rose slowly and steadily each day when they tested it daily in the hospital, and dropped perhaps twice as fast once off Coumadin.

6.) Adminitration of Vitamin K and or fresh frozen plasma (for emergency situations) caused a very fast drop. Trying to get the INR therapeutic again was extremely slow going. Doctors tried loading doses, but that didn't have much effect at first, then a couple of days later it would overshoot, and then ying and yang for a while.

Frankly, I think the loading doses were dictated by insurance people insisting that Joe get out of the hospital. I think his doctors would have preferred to just let INR levels get therapeutic slowly and steadily.

7.) Many meds cause INR problems

8.) I've seen more than my share of doctors scratching their heads over what to do.

So just based on Joe's experiences and what I have observed throughout the years in a non-professional way, this is what I think and it might not apply to everyone.

1.) Medical problems have a lot to do with INR management problems, CHF being one of the main culprits. Diuresis another culprit. Ascites a BIG culprit.

2.) Vitamin K and fresh frozen plasma work very well and fast to get the INR to drop like a rock.

3.) Loading doses are silly and just cause more problems down the road.

4.) Not every doctor knows what to do about Coumadin levels when they are difficult to manage.

5.) It appears that normally the INR creeps up slowly each day when it is below therapeutic levels. When loading doses are used, it might jump sharply and suddenly in an unexpected way.

6.) It appears that normally the INR lowers twice as fast as it rises.

7.) Coumadin is not easy to manage when there are co-morbidities and a lot of medications.

8.) Medical conditions that come and go like CHF, gout, kidney problems, liver and spleen problems make it very hard to manage Coumadin. And the addition of more medications to help these conditions and subsequent elimination of these medications once the problems get better, cause major problems.

9.) Most doctors and Coumadin managers need to take some additional education on Coumadin management. It's not a task that is well liked by most and they have a hard time trying to figure out the mathematics of it all.

 

[Ross]

This is an interesting topic for me because Im having challenges getting my INR into proper range for about the last month. I have a Coumadin Clinic managing my INR, checking it currently every two weeks.

8 weeks ago my INR was 1.7, as a result my dose was bumped from 30mg per week to 36mg
6 weeks ago my INR was 1.8, as a result my dose was bumped from 36mg per week to 42mg
4 weeks ago my INR was 2.6, as a result, no change still 42mg per week
2 weeks ago my INR was 3.2, as a result I was instructed to cut my dose for that night to 4mg and to stay at 42mg
Yesterday my INR was 3.6, as a result I was instructed to take 2mg last night and 4mg on Wed, all other days continue with 6mg. Next week I take 6mg every day except Wed, which will be 4mg. So net effect is 42mg down to 40mg.

I am happiest when my INR is between 2.0 and 2.5 so Im questioning if a 2mg reduction is enough, I thought at least 4mg.

Thoughts ?

Personally I wouldn't worry about it. It's between 2 and 4 and that's all that matters. To answer your question, I'd try 2 first, 4 may be too much.

 

[dick0236]

Al, very good question. I'll be interested in the posts that answer your question. I don't believe there is a "cookie cutter" solution for dosing between patients or even within the same patient. For me there have been many, many variables over the years that affected my INR:
Age - 31 then to 72 now
Weight - 140 then to 172 now
Metabolism - probably always been on the slow side
Activity - hyper-aggressive then to layed back now
Diet - Balanced then and balanced now, except less of it
Personal habits - "rode hard and put away wet" then. Don't get out of the barn much now.
Inherent variation in testing results due to ???
....and on...and on!!

Dosage levels have been fairly consistent with a downward trend from 70mg in early years to 35mg now. My INR range has always been 2.5 - 3.5.

Consistency in whatever I do is the key for me, knowing full well that there will occasionally be unexplained ups and downs in INR. There is only one ABSOLUTE for me. I DO NOT skip warfarin doses unless there is a theraputic reason. At "best" I will screw up my INR numbers and at "worst" I did irrevocable damage.

 

[Marty]

Six months ago Alice started warfarin because she was fibrillating after her pacemaker installed. The cardiologist told me anything over INR 2.0 was OK with him. I found her dose pretty fast 4mgm/day. We call in to a nurse in the cardiologists office every two weeks. This lady is pretty savvy in my view. She says anything between 2.0 and 3.5 is "therapeutic". No dose change. Since Alice has been "therapeutic" for some time ,the nurse says I only need to test her every four weeks now.The cardiology group is very happy with results from INRatio and Coaguchek. They insist results be called in to the warfarin nurse and placed in the patients chart since they are legally responsible.

 

[Guest]

Engineers are always trying to systematize warfarin. I think that Nancy got very close. There are so many variables that it doesn't seem to be systematized.

I have another theory - Iodine makes warfarin hard to manage.

Amiodarone is mainly iodine

Thyroid is affected by iodine. Thyroid controls the metaboliziation of the naturally occurring clotting factors.

Table salt may or may not contain iodine.

Guiafenesin cough syrup is mainly iodine.

Water at sea level contains more iodine that water in the mountains.

Iodine persists in the body for many months after signifigant ingestions.

So I think that iodine may be one of the major factors affecting the dosing of warfarin. How would anyone be able to analyze just these variables?

 

[catwoman]

Al:

That's an interesting theory about iodine and warfarin. Probably an accurate assumption.

 

[Guest]

I did a poster presentation an at big anticoagulation meeting in Washington DC showing this a few years ago. The big names in the field all looked at it, said, "Interesting", and walked on.

 

[Magic8Ball]

After nearly 2 years on the stuff i find that the only thing that affects my INR is the change between summer and winter.

In the back of my mind i think its more linked to drinking less water and drinking more coffee which tends to happen between summer winter.

Alcohol, food, exercise seem to do zip to my INR (not that i do much of the latter).

I work on the four day thing, my current dose every four days is 5,5,5,4....to maintain a 2.8/3.0 figure...

About time they invented an implant into the skin with a dial to display current INR....cyborg here i come....