NovembINR

[Ola Thoresen]

There are some graphs in the spreadsheet linked in the second post. (Notice there are multiple tabs, but only the first two is actually relevant, the third one is just one I have if I need to do some calculations).

 

[Jkm7]

First Congratulations on your recent engagement and all best wishes.
Second, your fiance's birthday dinner sounds amazing and I am truly jealous. We've enjoyed a few such but it has been a long time since.

Your experiment is very interesting and while I do not require warfarin, I am very interested in reading your posts. Thank you for sharing your experiments and results with us. Your efforts are appreciated.

 

[Protimenow]

Congratulations on the engagement. It sounds like a dinner that you'll long remember.

In my experience, the response to greens or other good sources of Vitamin K has been pretty rapid.

The issue with wine and beer may be somewhat different. The anticoagulation clinic that I use primarily to get prescriptions and to order lab tests that I can use to check against my meter(s) advises NO alcohol. I'm not sure that I understand everything in their protocol -- they seem to be happy with monthly testing, although I'm certain that your experiment shows some significant swings that would be missed with once-monthly tests.

The issue with alcohol is somewhat related to quantity consumed. Red wines are supposed to contain a component that can also effect your INR. The response to alcohol may also be related to your liver's ability to process the alcohol -- in theory, if your liver is stressed by the alcohol, it may metabolize warfarin differently than if it was a younger, healthier liver (this is just an assumption -- I really don't know).

It's often rather difficult to determine exactly WHAT causes particular changes, because we often don't have the ability to isolate a particular item to determine its effect. (For example, to eat ONLY brocolli(yuk) and nothing else). It can get more complicated if an interplay between more than one food can cause a particular effect, either amplifying or diminishing the effect of either component.

It'll be interesting to see how your INR fluctuates, but I suspect that it'll be awfully hard, if not impossible, to attribute changes to any particular entree.

 

[CATDOG]

Just saw this thread and plan to follow with interest. Based on your spreadsheet, I'm guessing you have 5 mg tablets and you take either 1.5 or 2 tablets daily. Theoretically, for the purposes of the experiment, it might be more accurate to have an even more consistent daily dose. If you set your pills out in a weekly box, I suppose you could even it up a tiny bit more getting down to quarter tablets but making sure to keep the same weekly dose. If your tablets are too crumbly, you might end up getting less than planned however. I'm mostly a 1.0 to 1.5 mg/day person, so I have tried cutting 1 mg tablets in quarters to even up the daily dose. If you are still in your "extra alcohol week", then you can toast to the pursuit of the scientific method. Good luck with your experiment!
CatDog

 

[Ola Thoresen]

Now, this is intriguing...

Today my INR was 2.7 again. To me that implies that alcohol itself does not have a big effect on my INR-level (YMMV). There is nothing I have eaten the last couple of days that should counter the impact of more than 10 glasses of wine and beer, if alcohol itself had played a major role. But of course there might be - as Protimenow explains - other components in certain wines that will cause a rise in INR. Now - I could certainly do a long study on this, testing everything from pure ethanol to a bunch of different vineyards and grape sorts - and even different beers, but time and money (and probably my liver) does not allow such an experiment at least for now.

But for me, the most important conclusion drawn from this, is that it does not seem to be a problem from an anti coagulation perspective to drink at least moderate amounts of alcohol, even several days in a row.
I do not have to worry about excessively high INR values even after the Christmas party, or after going on a camping trip with the guys for a weekend. And IF I see a raised INR after such an event, I can rest reasonably assured that the INR will go back to a normal level quite quickly.

Next week - how much green vegetables will I be able to eat in three days?

 

[pellicle]

Hyvää Huomenta alkaen Suomessa

Now, this is intriguing...

science always is

Now - I could certainly do a long study on this, testing everything from pure ethanol to a bunch of different vineyards and grape sorts - and even different beers,

sounds attractive, if you need more subjects in a non-randomised cohort please let me know

but time and money (and probably my liver) does not allow such an experiment at least for now.

not to forget fingertips ;-)

Next week - how much green vegetables will I be able to eat in three days?

I bought a bundle of asparagus this week so I too will be interested in my own 'experiment'

its been tasty too.

 

[Ola Thoresen]

Just saw this thread and plan to follow with interest. Based on your spreadsheet, I'm guessing you have 5 mg tablets and you take either 1.5 or 2 tablets daily. Theoretically, for the purposes of the experiment, it might be more accurate to have an even more consistent daily dose. If you set your pills out in a weekly box, I suppose you could even it up a tiny bit more getting down to quarter tablets but making sure to keep the same weekly dose. If your tablets are too crumbly, you might end up getting less than planned however. I'm mostly a 1.0 to 1.5 mg/day person, so I have tried cutting 1 mg tablets in quarters to even up the daily dose. If you are still in your "extra alcohol week", then you can toast to the pursuit of the scientific method. Good luck with your experiment!
CatDog

I use 2.5 mg tablets, and I have considered splitting them, so instead for taking 4,3,3,3,4,3,3 I would take IE 3.5, 3, 3.5, 3, 3.5, 3, 3.5 or even 3.25, 3.25, 3.25, 3.25, 3.25, 3.25, 3.25.

But the half life of Warfarin is quite long, which means that the real variation is not very big as long as you administer the pills fairly even.
I made a graph here which shows this:

(This graph is not really accurate, it only takes into account that the half life of Warfarin is 48 hours, and that it is completely out of the system after 96 hours, and that the break down process is completely linear, which is of course not true. But it shows the point, that the Warfarin level in the body does not fluctate very much.

Column G is what I do today. 10 mg Monday and Friday, 7.5 mg the rest of the week.
Column J shows how many mg I would have in my body if I used an altering scheme of 3.5 and 3 pills (8.75 and 7,5 mg) every other day instead.
Column M shows a base for how it would be if I had taken 3,25 pills (8,125 mg) every day.

As you can see, the peaks and valleys of my current situation is obviously higher and lower than the other two, but the variation is still not more than about 2,5 mg (+/-10%) of the "ideal".

 

[Ola Thoresen]

A weekend without much to report.

For some reason my INR was 3.1 today. The highest I have measured since NovembINR started, but it does not really worry me. Today also marks the start of my "green" week, so I'll have salads for lunch today, Tuesday and Wednesday, and also have extra green vegetables for dinner these days. Unless my INR really drops, I'll keep my dose of Warfarin as usual, to see how quickly I recover without doing any adjustments.

 

[pellicle]

Column G is what I do today. 10 mg Monday and Friday, 7.5 mg the rest of the week.
Column J shows how many mg I would have in my body if I used an altering scheme of 3.5 and 3 pills (8.75 and 7,5 mg) every other day instead.
Column M shows a base for how it would be if I had taken 3,25 pills (8,125 mg) every day.

I'm a little lost ... what is your dosing regime?

 

[Ola Thoresen]

I'm a little lost ... what is your dosing regime?

Currently ("Column G")

Monday: 10 mg (4 tablets x 2.5 mg)
Tuesday: 7.5 mg (3 tablets x 2.5 mg)
Wednesday: 7.5 mg (3 tablets x 2.5 mg)
Thursday: 7.5 mg (3 tablets x 2.5 mg)
Friday: 10 mg (4 tablets x 2.5 mg)
Saturday: 7.5 mg (3 tablets x 2.5 mg)
Sunday: 7.5 mg (3 tablets x 2.5 mg)

Total: 57.5 mg / 23 tablets


The other lines are just for reference:
Column J:

Monday: 8.75 mg (3.5 tablets x 2.5 mg)
Tuesday: 7.5 mg (3 tablets x 2.5 mg)
Wednesday: 8.75 mg (3.5 tablets x 2.5 mg)
Thursday: 7.5 mg (3 tablets x 2.5 mg)
Friday: 8.75 mg (3.5 tablets x 2.5 mg)
Saturday: 7.5 mg (3 tablets x 2.5 mg)
Sunday: 8.75 mg (3.5 tablets x 2.5 mg)

Total: 57.5 mg / 23 tablets


And

Column M:
Monday: 8.125 mg (3.25 tablets x 2.5 mg)
Tuesday: 8.125 mg (3.25 tablets x 2.5 mg)
Wednesday: 8.125 mg (3.25 tablets x 2.5 mg)
Thursday: 8.125 mg (3.25 tablets x 2.5 mg)
Friday: 8.125 mg (3.25 tablets x 2.5 mg)
Saturday: 8.125 mg (3.25 tablets x 2.5 mg)
Sunday: 8.125 mg (3.25 tablets x 2.5 mg)

Total: 56.875 mg / 22.75 tablet


So Column M is slightly less than the other two - 0.25 tablet or 0.625 mg in a week - but I do not believe this would cause any significant change in my INR level.

 

[Ola Thoresen]

Oh, and the reason I don't go for option 2 ("Column J") is that the tablets are really small and quite hard to divide. So since the difference in variation is so small, I don't believe it is worth the extra effort to try to divide them in 2 (and even less reason to try to divide them into 4 which would be needed for the 3. option ("Column M")).

 

[pellicle]

Hi

Currently ("Column G")

Monday: 10 mg (4 tablets x 2.5 mg)
Tuesday: 7.5 mg (3 tablets x 2.5 mg)
Wednesday: 7.5 mg (3 tablets x 2.5 mg)
Thursday: 7.5 mg (3 tablets x 2.5 mg)
Friday: 10 mg (4 tablets x 2.5 mg)
Saturday: 7.5 mg (3 tablets x 2.5 mg)
Sunday: 7.5 mg (3 tablets x 2.5 mg)

Total: 57.5 mg / 23 tablets

interesting, so you have a cycle of +***+**+***+**+***+**...
+ is 10mg
* is 7.5mg

which is good because some people end up with back to back high doses because they forget that the week cycles around in a circle. I wonder if you have found any variance in your INR after the three days of 7.5 compared to two days of 7.5? (since you are measuring daily)

My daily average is 7.1mg which I've been able to do by splitting a 1mg tablet and having that every second day with my regular dose of 7mg. That has been where I've settled into. Personally I found that I seem to have some sort of hysteresis point where if I go much over that my INR ramps up fast. For instance below is my current INR / Warfarin dose graph

you'll see that it was steady at one point, but then from about 35 (y axis is weeks ... sorry) it changed and I needed to revise my doses (this is the week I traveled to Finland but there are many other factors at the same time). I'm not entirely sure its settled down, but the move from 7mg to 7.1mg has me in a better place (as I prefer to keep away from the 2.0 line as my 'INR range' was defined to me as 2.2 ~ 3.0 by my surgeon.

When my INR is trending "low" (like point 25 and 45) I set up an adhoc measurement rather than wait a week. If its picked up of its own cyclic accord I don't adjust dose (although I did on 25 because it was out of range and wasn't coming back).

Your work is very interesting, thanks for sharing it.

 

[Ola Thoresen]

Just for fun, I created an INR-level graph based on the warfarin-content graph. Seems like for me, just dividing the warfarin-level by 6.25 is a good estimate.
This is of course even more inaccurate than the warfarin-content graph, but you get the idea of the theoretical variation during the week:

My current regime (the yellow line) should then give me max 3.0, min 2.6, which is very much where I would like to be.
By choosing the other potential regimes, I could straighten it out a bit to max 2.8, min 2.65 (blue line) or an even 2.7 (purple line).

To the question of whether I can see this in my measurements now, I think I must say "no" - at least not yet.

To count for the delayed effect of Warfarin, I have skewed the graph slightly. This might or might not give the best results. I have to experiment a bit when I have more data. My current idea is that a high(er) dose of warfarin on Monday would give a higher warfarin-level on Tuesday, and a that would give a higher INR on Wednesday.

The prediction of this graph would then be that Saturday should have the lowest INR-level (~2.6) and Wednesday should be highest (~3.0). The first week I measured every day, Saturday was actually lowest (2.3), but I did not do any measurements on that Wednesday.
However this week, Saturday was the highest (3.0) even if I had lots of alcohol both the weekend before, and on Monday-Wednesday (my weeks start on Monday). Wednesday was actually slightly lower (2.9), but all over, the week varied most between 2.5 (Monday) and 3.0 (Saturday), whereas the rest of the week was 2.7 - 2.9.

All in all, I think these variations are so small that all other biological processes probably count for more than the half time and delayed effects of warfarin.

 

[Ola Thoresen]

... And I just had to check...

Here is a comparison between the theoretical value from the previous graph and my actual measurements the last week and a half.

Maybe there is something there after all. Looking forward to following the development.

 

[pellicle]

interesting .. quite close to eachother (allowing for variance)

 

[Ola Thoresen]

I have now added this "Theory"-graph to the bottom of the "Graphs"-tab in my original google spreadsheet:

https://docs.google.com/spreadsheet...o2NHltU2JSdGxWQUU1blFzNXc&usp=drive_web#gid=1

Interesting...

 

[Protimenow]

It's probably not accurate to describe what happens with Warfarin in terms of 'half life.' What you're saying is that, for most people (perhaps some metabolize warfarin at different rates), the MAXIMUM result, in your case, is seen 48 hours after you take it. If the 'half life' theory was in effect, the effects would diminish, so the effect of the dosage 48 hours later would be 1/2 of what it was when the maximum effect was realized.

Probably the only way to demonstrate this curve would be to have someone who isn't already taking warfarin take a dose, and monitor the INR daily. For the rest of us, who take warfarin every day, the results may overlay what's probably a pretty steady state of warfarin in our systems. We'll see spikes and valleys based on previous doses, but it may be less reliable to try to correlate any particular INR with a dose of a day, two, or more earlier.

 

[Ola Thoresen]

Right now I'd love to have unlimited access to test strips. Unfortunately I only had 24 extra...

 

[Protimenow]

As a person who has run through a LOT of strips testing (in my case, multiple meters), I understand your situation.
These studies have probably done many times - probably on dogs - but may have have been well reported.

It's good to see the testing that you ARE doing.

 

[Ola Thoresen]

It's probably not accurate to describe what happens with Warfarin in terms of 'half life.' What you're saying is that, for most people (perhaps some metabolize warfarin at different rates), the MAXIMUM result, in your case, is seen 48 hours after you take it. If the 'half life' theory was in effect, the effects would diminish, so the effect of the dosage 48 hours later would be 1/2 of what it was when the maximum effect was realized.

One issue with all these tests and theories is that in reality a day is not a day. I don't eat all my meals at the same time. I eat some meals in the morning, some in the evening. Sometimes I drink a few beers just after work. Sometimes in a weekend I can have a drink in the middle of the day. Some nights I stay up really late and eat or drink in the middle of the night... So the effect of anything happens gradually and disappear gradually. I am here only counting when I actually check my INR, and in that sense a day is a day, no matter what time of that day I eat my broccoli.

But I also measure the INR at about the same time as I take my daily dose of warfarin (usually in the morning). So if I increase my dosage on Monday, I would obviously not detect that the same day. If I actually checked the amount of warfarin present in my body, it would probably take a few hours before it is even detectable - going through the digestion system and all that. So the next day would be the earliest I could see any difference.
And then that warfarin has to "do its thing". So even if it started working - say two hours after I took the pills - it would then probably take at least 24 hours, if not more, before I could detect any significant effect on the INR. If I had checked in the evening, I could probably detect some of the effects of what I had done that day already the same day. But this is the reason I test in the morning. I want to check the effect of what I did yesterday (and the days before) and not have any interference from the testing-day.

So the max would obviously not be exactly 48 hours after the dosage, but that would probably be the time I would measure it, since I only check once a day, not every hour.

The next day, 72 hours later, I believe the effect would have started to diminish as you say, and then gradually disappear. However, by that time, I have already had two more doses, and each of those would go through the same stages. So the max could be before or after 48 hours, but my belief is that it is longer than 24 hours and shorter than 72 hours. That only give me 48 hours left to choose for the testing.
As far as I know, there is also no reason to believe that the INR peaks at the same time as the warfarin dose in the body is at its maximum. First the warfarin has to stop the vitamin k from making the liver form the coagulation elements, and then the old clotting proteins have to "die" in a great enough number to have an effect on the decreased clotting. So the INR level could probably keep on increasing even after the warfarin level is on its way down, before the body recovers and the liver has produced enough new chemicals.



The reason I only calculate 96 hours (4 days) back in time in these graphs is because it is much easier, and because I do not believe the added complexity from even more detailed graphs would add much value.
As an example: If half life of warfarin is about 48 hours (Wikipedia states 40 hours), then a dose of 10 mg would be "worth" 5 mg after these 40 or 48 hours, and only 2.5 mg 40 (48) hours after that again.
But in those 96 hours I would have added at least 3*7.5 mg (22.5 mg) in new doses, so the first 10 mg is only counting for about 10% of the total "warfarin value" on that day.
After another 24 hours, these original 10 mg would now be degraded to slightly less than 2 mg, and I would have added 10 mg more from another dose - a total of 32.5 mg in those 5 days.
So that means that after 5 days the original 10 mg would count for only 5% of my total warfarin-level.
But because I believe the maximum effect is taking place more than 24 hours after a dose is taken, I skew the theory-graphs by 24 hours and 48 hours respectively. So as I said. A high dose on Monday would be measured as increased INR on Wednesday. If I had checked every hour, the actual max could be sometime Tuesday evening, or it could even be later on Wednesday (so the actual max is higher than I measure), but on Thursday, the effect of that dose would start to be smaller and by Friday or Saturday it would probably be more or less zero again.

In a true sense of "half life", nothing ever disappear (hello homeopathy), but in real life, the effect of a medicine is negligible after a few halvings.