Missed 2 days of Warfarin - Pellicle's Model??

[newmitral]

I have on rare occasions missed taking my warfarin for one day. Typically, when I realize this, I just pick up and take my normal dose and get on with things. Normally I take my warfarin in the evening with dinner. Once or twice I took an extra half dose the next morning after resuming my normal dose the evening before, but it has not made much difference in time to get back to normal INR range.

This evening (Monday), however, when I went to take my warfarin dose, I saw that the pills for Saturday and Sunday were still in their little compartments of my pill minder. So now, for the first time, I have missed two consecutive days of my warfarin dose. Comments regarding the "Forgotten Weekend" are deserved.

I took 1.25 times my normal dose this evening. My plan is to take an extra half-dose tomorrow morning (about 14 hours after my normal dose. Then, I plan to resume my normal dose tomorrow (Tuesday) evening.
I will test my INR tomorrow evening again when I take my pills, and if I am still below 2.0 I will take another "extra" 1/4 dose Tuesday evening followed by another 1/2 dose Wednesday morning.

I thought that this would be an interesting opportunity to test Pellicle's spreadsheet model of what the optimum strategy should be to return to within range in the shortest time, without risk of serious overshooting, based on his model's prediction.

I home test, and fortunately, I took my INR reading Saturday morning, just prior to the time I missed the doses Sat & Sun evenings.

My range is 2.5-3.5 (target 3.0). On Saturday morning, my INR was 2.8.

Monday evening (just now) my INR is down to 1.5.

I take a lot of warfarin (12.5/day) and my INR drops like a rock when I miss a dose (or 2).

So, I'm curious to see if Pellicle's model would lead to a different predicted optimal recovery strategy than I have outlined above.

I look forward to the reply.

 

[Freddie]

FWIW. it takes approximately 3 days for a dosage change to be noticed.
Personally I would go back to my normal dosage (in your case Tuesday) and test on Wednesday & Friday.
By Wednesday you should see a small increase in your results,

 

[pellicle]

Hey there newmitral ... was thinking about you the otherday

So, I'm curious to see if Pellicle's model would lead to a different predicted optimal recovery strategy than I have outlined above.

I look forward to the reply.

did you make an INR reading as soon as you knew you had made that mistake? Good to have a baseline to start from. I know when I've done "whopsies" I take readings daily to plot it.

I'm also very interested to see your results ... one thing, the lag time on a dose and an INR change will be at least half a day (bio-availability is high, but by the time it begins acting on the Vit K and that in turn begins acting on the coagulation cascade it may take a day to see a change attributable to the warfarin.

looking fwd to your results

PS: Freddie I disagree with the common view that it takes so long .. when I go off warfarin (like when I forget or like when I have been directed to) the drop is observable fairly soon. I suspect that the "three days" is a simplification of things to make it easier to communicate

 

[pellicle]

newmitral

here is a graph of my data from 2014 when I was actually keeping an eye on my "high" inr 13 Dec and took a mid week reading to be comfortable that it was going to turn back (it did) and used that data as a pre-event set for when I took the dose twice (don't ask) ... I double dosed on 1 Jan 2015 and the readings after that (point 20) show the reactions to my double dose with daily measurements.

in conjunction to watching it plummet when I missed doses this cemented to my mind the fallacy of the "takes days" to see any effect.

Interestingly the actual INR measurements were close to the 2 period moving average of the model prediction

a less "busy" chart of the same period is this one:

which shows just daily dose vs INR (with bars indicating actual measurement days)

 

[newmitral]

FWIW. it takes approximately 3 days for a dosage change to be noticed

.

Hi Freddie,
In my case, I see results of a dosage change much sooner - usually within one day. As the results I first posted above show, in only 2 days I have dropped from INR of 2.8 to INR of 1.5 (between Sat morning and Mon evening). I suspect (although this is just my personal theory - not supported by any particular study) that the more warfarin you need to stay in range, the faster you react. I base this hypothesis on the assumption that my metabolization of the warfarin is fairly quick, which is why it takes so much for me to stay in range (12.5mg/day).

did you make an INR reading as soon as you knew you had made that mistake?

Hi Pellicle,

Yes, as I posted above, I took a reading Monday evening, the same evening I realized that I had missed the pills on Saturday and Sunday. That INR reading was 1.5
I suspect the international date line creates a bit of confusion, but it is still Monday evening here. This just happened within the past 2 hours.

I do plan to take INR readings daily as I recover from my screw-up. I'll check INR tomorrow evening just before I take the Tuesday pills to determine if I should take normal dose or higher. I will base this decision on whether or not I am below 2.0 at the time.

I was curious whether you had modeled the situation of missing 2 days, and if so, what your model shows as the fastest return to range without overshooting too much on the high side. Because I take such a large amount of warfarin, I don't want to just take 1.5 times my normal dose for 2 or 3 days as I may then go too high.

 

[pellicle]

.

I do plan to take INR readings daily as I recover from my screw-up. I'll check INR tomorrow evening just before I take the Tuesday pills to determine if I should take normal dose or higher. I will base this decision on whether or not I am below 2.0 at the time.

bewdy ... data data data ... say on that subject if you are interested in collaborating with some data I have a project on the boil atm. More data would be helpful. Please email me at my username at hotmail

I was curious whether you had modeled the situation of missing 2 days, and if so, what your model shows as the fastest return to range without overshooting too much on the high side. Because I take such a large amount of warfarin, I don't want to just take 1.5 times my normal dose for 2 or 3 days as I may then go too high.

I sort of have, as that's what happened when I had my first debridement operation (they took me off warfarin the day of the surgery (meaning I took my dose in the AM as always, had surgery in the PM and was off for 2 days after that). I did not have INR done during ICU stay, but back on the ward they took blood and did INR daily ... that data is presented in this chart:

 

[Bina]

Somebody has been very naughty..............missing TWO doses........ Do I need to go over there and smack you ?
I am a worrier, so if my INR had dropped down to 1.5 that would send me to the local ER for a quick Lovenox shot until the regular daily Coumadin doses could catch up over a couple of days.
Good Luck !

 

[pellicle]

Somebody has been very naughty..............missing TWO doses........ Do I need to go over there and smack you ?

a spanking a spanking ... there's going to be a spanking

[ link ]


{for our American cousins, this is a scene from Monty Python's Holy Grail comedy}

 

[djacq]

Bina is right!!! In fact, I was instructed and had a prescription for Lovenox to use if my INR went below 2.0. I have been given different information about how long you can go on without Coumadin. Some say it can be awhile as the aortic blood flow is faster than from the other valves. BUT, know in spite of my careful home testing, never missing a dose and Lovenox use at home, I developed a clot on my mechanical valve. I had anemia issues and my testing equipment had to be changed. PLEASE use a med minder and you can even get one with an alarm to remind you to take your Coumadin and listen to Bina.

 

[pellicle]

perhaps of interest to folks with modern bi-leaflet pyrolytic carbon valves (St Judes regent, On-X, ATS, ...) in the Aortic position is this paper:
http://circ.ahajournals.org/content/123/1/31.short

patients were studied 1994 and 2006 who were divided into two groups: Ross procedure and Mechanical valves.

Patients were randomized
between a conventional group (international normalized ratio [INR]
target range, 2.5 to 4.5) and a low-dose group (for aortic valve
recipients, the INR target range was 1.8 to 2.8).

During follow-up, 5 Ross patients and 1
patient with a mechanical valve experienced a thromboembolic
event.

naturally each person must evaluate their own situation and act accordingly. Just because a study across 1700 odd patients got X Y or Z result does not mean that you will get that yourself.

I personally don't get worried if my INR dips below 2, but I do then monitor it every 2nd day or so and hit up my dose a bit should I observe it's not moving up. I'm not really in a position to speak from much personal experience as I've only had my mech valve since 2011, so not long yet really.

 

[newmitral]

Somebody has been very naughty..............missing TWO doses........ Do I need to go over there and smack you ?
I am a worrier, so if my INR had dropped down to 1.5 that would send me to the local ER for a quick Lovenox shot until the regular daily Coumadin doses could catch up over a couple of days.

Hi Bina (and Pellicle),

I remember some Loony Toons cartoon character from my youth saying:
"I've been a baaaaaaaaaaaaad boy" and was hoping to find a clip of that to post in reply, but sadly I can't find it even after much googling.

I do have on hand some Lovenox from when I bridged for a prior surgery. It's a bit past its expiration date, but even if it is a bit reduced in potency it will afford me some extra protection until the warfarin kicks in.

PLEASE use a med minder and you can even get one with an alarm to remind you to take your Coumadin and listen to Bina

.

Hi Djacq,

I do use a minder, but my point of failure seems to be that I have been taking my warfarin with dinner, and the minder is in the kitchen. If I eat out at a restaurant, however, I have to make an extra mental note to take the warfarin once I get home for the evening. This is the problem since it is a break in the routine, and I often just forget once I get home. I'm changing my routine as a result of this 2-day oversight, and have moved the minder to my bedside night-stand so I'll take my warfarin each night before bed instead of at dinner. I figure I'm less likely to forget once my routine is changed.

 

[pellicle]

Hi

what sort of phone do you have? I have alarms set on mine to remind (nag) me. Last thing before bed is a good time if you ask me. I also have learned to pack my pill box when I go on trips (which break my routines), on those occasions I rely on my alarms and on the small habits of placement of stuff like toiletrys in the hotel ... inspect the canister before going to bed.

no matter what, S will still hit the Fan ... that's life.

 

[gregjohnsondsm]

I am just starting on warfarin. Started at INR 1.1. It has been 6 weeks and they only test me every week but INR values have been 1.1, 1,.2, 1.4 ,1.5,1.6,1.8,1.4. With increasing doses. Now at 7.5 mg per day. My question is: doesn't it seem reasonable that the body has some natural control system to try and maintain the coagulation values at normal range? And wouldn't this system be fighting the warfarin so when I got to INR 1.8 they kept me at the same dose for the next week. But my INR went down. Anyway is here some time required to overcome the bodies attempt to keep the INR normal?

 

[Freddie]

Don't despair gregjohnson, it took me months to get into my range. As for the small drop from 1.8 to 1.4, it was probably due to something you ate.
But don't fret you will get there and testing once a week until you are in range is normal.
As for the ones 'system' trying to fight the warfarin, I don't think so. Warfarin depletes the vitamin k which is the clotting agent in the blood.

Hope this helps

 

[pellicle]

Hi

I am just starting on warfarin. Started at INR 1.1.

gotta start somewhere and starting low and moving up slowly is the best way. There are some potentials for problems when starting, especially if you hit in too fast. So I reckon you're on the right track

It has been 6 weeks and they only test me every week but INR values have been 1.1, 1,.2, 1.4 ,1.5,1.6,1.8,1.4.

weekly testing is a good frequency, It prevents "over correction" ... just like learning to powerslide a bike or steer a sail boat. Steady as she goes.

With increasing doses. Now at 7.5 mg per day

that's about my dose ...

My question is: doesn't it seem reasonable that the body has some natural control system to try and maintain the coagulation values at normal range?

it does, and the warfarin is the spanner in the works on that. So like gravity pulls your bike down the hill faster brakes are the friction applied to keep a constant speed

And wouldn't this system be fighting the warfarin so when I got to INR 1.8 they kept me at the same dose for the next week. But my INR went down. Anyway is here some time required to overcome the bodies attempt to keep the INR normal?

being an ex biochem kinda fellow and being of the homeostasis camp that's what I initially anticipated would be the go when I started too ... however it seems that such is not the case. I've since learned that there is no direct mechanism in the body that attempts such things and that the "coagulation" levels are holdable with the application of warfarin that interferes VERY specifically with on part of a precursor to the cofactors.

There is instead a mechanism to break down the "spanner" (warfarin) and that's encapsulated in the Cytochrome P450 pathways. These work on breaking (inactivating) and then breaking down warfarin (for disposal). These work at a set rate (which depends on your metabolism and your genetics) and thus there is a "new" homeostatic mechanism created by introducing warfarin and essentially keeping the coagulation pathway "in arrears" all the time. We have well over 50 years of research and observations in this area.

Anyway, in my case I've found that my INR responds significantly to small dose changes in warfarin yet is relatively unaffected by diet. This is something which I believe is known by INR managers too and why they don't want to elevate you too rapidly

I've deliberately had weeks of meat n potatoes followed later by other weeks of spinache every day to see what effects there are ... I now feel comfortable that the alterations are insignificant (don't do grapefruit juice daily though).

here is 2013 data:

you can see that my dose never varys much but changes in my "metabolism" seem to influence how it reacts. Almost like a sine wave that spans weeks. I have been unable to determine a basis for this cycle.

I believe that you'll find such a graph common among "stable" AC therapy patients, and its only the ignorance of some AC clinic managers who try to hold it down more than that.

Here is 2014

note the scale on the RH Y axis to see the dose variation isn't really big (but I wanted to examine it carefully)

Speaking numbers, a target of 2.5 with a range of between 2 and 3 is considered "normal" for aortic valves. So my "average" over 2014 was 2.6 with a standard deviation of 0.4 ... that's pretty darn good. I was also 91% in range with my max during the year of 3.5 (not harmful) and min 2.0 (also not harmful)

This chart shows the range where problems are minimised:

Best Wishes

 

[gregjohnsondsm]

Pellicle. Wow. Nice data and relevant information. As you have pointed out in some of your other very informative posts : the changer in INR is really much faster than the three days most technicians tell us. If so why is it taking so long for my levels to get in the 'safe' range? They seem to be climbing so slowly. I was thinking this may be due to the bodies system renormalizing.
Anyway thanks for your research. Very helpful and appreciated. This and your other posts.

 

[pellicle]

Hi

Glad to help if I can

.... If so why is it taking so long for my levels to get in the 'safe' range? They seem to be climbing so slowly.

Well not totally sure, but my logic on the dynamics is that if your system is breaking it faster than your intake rate then your intake rate will need to increase. I was sort of thinking of the case of newmitral who takes 12mg to be in range.

There are some who require as much as 20mg and others who only need 4mg

Its possible that a genetic test could assist in determining your metabolism, but careful empirical observation and slow increases will determine it too.

Keep us posted on your progress, I at least am interested.

 

[pellicle]

Hi

Just a quick thought could you provide the daily dose with those INR values?

t INR values have been 1.1, 1,.2, 1.4 ,1.5,1.6,1.8,1.4. With increasing doses. Now at 7.5 mg per day.

 

[gregjohnsondsm]

Now they took me to 10mg / day for 1 week and my INR was 3.6! And I have a lot of blood in my stool this morning. The whole bowl was full and bright red. They want me to change to 9mg on tue and thur and remain at 10 for the rest of the week. This doesn't seem like much of a change to get me back to 2 -3 level. What level is dangerous?
For pellicle, I will get the dosages for the above INR values (previous post) I just don't have the data right here.

 

[Boomanchu]

I imagine that we're all different but my first week of ACT after surgery I was a bit low taking 5 per day so I was told to take 10 for a week then retest. I thought this sounded crazy. I tested at 7.9 a week later and I noticed no I'll effect. Skipped 2 days and went to 5 a day and have been steady since