understanding INR range and variation using statistics

I've been working with managing my INR for some 14 years now (so, not really long), but as well I've helped a few others along the path of being able to self manage. This has been not only helpful for them, but a great learning experience for me too. One of the things I've had to do is teach an understanding of how to use basic statistics to help understand things. Things like the data we have about our INR. Lets look at this set of data, remember, these are daily measurements:

This person was just starting their warfarin therapy and we were working out the optimal dose required for them. We had to make some adjustments but we ended up on 9.5mg daily. You can see from the above that there are some ups and downs;

• for the most part we've been at or above 2
• we've kept times above 3 small (being even as high as 4 isn't really significant)

What we don't really know is "how well we meet the ideal target of 2.5" which was set by the doctors. We could average all those numbers and then know that. In this case the average was 2.57, so that's great! But if we ask "is this variation large" we don't really know. This is where some statistics tools comes in handy.

Statistics is something most of us use but try hard to ignore (probably) because of the trauma of high school maths classes; but we shouldn't because its really helpful. One doesn't need to know how to do the hard work to get the benefits because spread sheets have all this functionality built in; all you have to do is have the data in a column and use a formula to get it all worked out for you; write in =AVERAGE(E20:E130) and there it is.

I'm pretty sure most people are comfortable with average, but alone, average isn't helpful, you need its good mate the Standard Deviation. Lets go with an example: You know that the average height of 16 year old boys is 173.5cm. You have a boy from a class who's 185cm. So the question is "is he very tall or not really unexpectedly so"?

Intuitively we know that the answer is no, because we have experience with children. But if we also find out that the standard deviation is 7.4cm we know that anything between 166.1cm and 180.9cm is a totally expectable result. We know this because that is what Standard Deviation (SD) is designed to measure. Below is a curve which is called a "Normal Distribution", people who have been working in statistics for years know this curve well.

the Normal Curve

It shows us that 68.2% of people (in this case, but its also more generally "of measurements") will fit between -1 SD  and +1 SD (we use the lower case for Greek symbol sigma σ to represent SD which you'll see on the bottom axis of that graph of the Normal Curve).

So just like we know that most boys age 16 are between 166.1cm and 180.9cm we can use the SD to work out how much variation that person has from "the population". The SD for the data in that bar chart above is 0.41, which means that any variation we see where the INR is between 2.16 and 2.98 is entirely normal for this person. Note: we don't know about you because we don't have your data.

Next, looking at this we can see that quite a portion (about a quarter of all measurements) fall within 2 SD either side of the average (or μ) which means INR readings of 1.75 through to 3.39 are to be expected, but just not often. Also 1.34 through to 3.8 may come up (however rarely) and this would be statistically rare, but not impossible.

So how does this help us manage our INR?

It helps to know that if your regularly and reliably taking your regular dose and if you're regularly seeing your INR within 1SD of the average then you shouldn't really make any changes in your dose. Keep your dose consistent and you can then rely on the statistics to understand what is normal for you.

Looking back at the graph of INR we also see something else ... from measurement to measurement we typically don't see that much change. Sure there are a couple where "day to day" we saw substantial on the 1st of August where INR fell from 3.3, through 2.7 (next day) down to 2.3. This was the result of some changes; dose was dropped to 8.5 and it fell fairly quickly but as you see didn't drop below 2.1. The INR then ranged back towards the average within a week.

The approach we should have taken was "keep a steady hand on the tiller" combined with waiting for a few more readings. However ...

As a good (budding) statistician, if you do see a reading which is outside of the 1SD range and you know that nothing has changed (no new foods, no binging on grapefruit, no binging on greens) then you should expect it to gradually change back towards the average. Unless something has changed and you don't know it. If it stays higher then you know "something has changed" and investigation is warranted into what.

So, please do make friends with  both average and SD, incorporate that into your spreadsheet as well as using regular weekly measurements. Occasional mid week samples "just to know" are also often helpful, but as you can see from both the historical experience behind Average and SD, combined with regular dose and weekly readings you can be in INR range in the high 80% of the time.

To get into the 90's you just need a few more strategies ... but that's for another post.

Best Wishes

Lancet sizes - INR vs Blood Glucose sampling

For whatever reason people seem to find themselves asking for advice about getting enough blood, one of the problems is often as simple as not using the right lance. The right lances are supplied with the Roche CoaguChek system.

Note the words CoaguChek, not Accu-Chek ... those are for blood glucose testing and the blood drop size difference is significant. I don't have Accu-Chek, but I do happen to have a different brand which is designed for blood glucose testing called Contour.

The key point is gauge (or diameter). Lets take a look at what I mean. I'm sorry, that magnification is not identical, but the table that follows shows this:

CoaguChek

Contour

to back this up lets look at the measurements I took with my calliper

more than double the thickness...

The point of the exercise is to lance to a minimum depth necessary to get a sufficient sample of blood.; not to create a bigger wound. A bigger diameter wound channel is better for bleeding than a smaller diameter. 

Lastly make sure you're lancing on the side of the finger (as the manual suggests) to avoid harder thicker skin on the hand and to minimise cumulative nerve damage from lancing the same point.

HTH

Roche CoaguChek XS PT Test vs PT Test PST

So, today I found out something interesting. Roche has two slightly different versions of the XS PT strips, this apparently is related to the INRange series of devices. I went to order some more strips from my (online) provider (here in Australia) and found the following two products (at different prices). There is the XS PT Test (which I've used for well over 10 years).

And the new kid called the XS PT Test PST (probably with KyB4 and other enhancements)

I'm seeing that this one has INRange written  on it as well as XS written on it. Further to the best of my knowledge the INRange is the same and compatible with the XS and as a unit simply has some additional features more conducive to working in a Clinical setting, such as the ability to interface with a computer, multiple ID tags (presumably to differentiate different patients) a nice colour screen (whoopdie  do) and a graph (I prefer what I do in Excel).

So I rang Roche (in Australia) and spoke with a "Technical Support" officer who informed me that the two were interchangeable but there may be some differences in electronic communications. She was surprised when I said that my seller has a different price on the XS PT Test vs the XS PT Test PST.

She also said to me that she thought that the difference between the names was PST was for "Patient Self Testing" ... (making me wonder what's happening over there in the Good Ole US of A)

All very interesting. Given that I have the XS (and not the INRange) I'll be using the earlier (and cheaper) ones in my XS ... 

This is the new (looking golden) and the old (poor camera colour balance on my part)

Everything (including the amount of stripes of contact points) seem to be the same.

Anyway, that's all I have today.

Some other details about the Roche CoaguChek XS

The Roche CoaguChek is pretty much the backbone of my personal self management of my INR. I have on many occasions discussed that I compare it to the lab and often get quite good (less than 0.2INR units) correlation with labs. This is something which is occasionally still debated (particularly on the internet) but which to my mind was put to bed back in 2012 with many comparisons of its accuracy vs that of other systems. So I'll not waste your time and repeat that here.

Determining INR is based on measuring the time taken for "coagulation" to occur.

Note: That's a minefield right there, so lets just leave it simply at: a timer is started and stopped when the machine determines coagulation is "completed" (*according to guidelines like reagent ISI, another rabbit hole for you the curious).

The CoaguChek uses "amperometric electrochemical" methods for determining the time to declare the point of "coagulation" to stop the timer. A good summary of this and other methods is here (link).

So having swept that detail off the table, I wanted to get down to exploring a little bit about the CoaguChek XS system which we can easily see, but may not have noticed (even if you've used one).

First, lets have a quick look at the strips, they are much bigger than the strips used by Blood Glucose monitoring strips. Shown below.

Obviously the strips above are used because I prefer not to risk contaminating them for photography and so you'll see traces of my blood in these images. Note that circular hole in the strip at about the 24mm point. I'll circle back to that.

This video gives a quick walkthrough of the XS. 

As you saw in that video the CoaguChek strips have three layers of plastic, seen in the image below. 

The top printed layer is white, in the middle is a black layer which is used to form the blood capillary tube and then there is a clear base layer (which I'll call the substrate). I can't measure the thickness of the black layer, but I used my trusty digital callipers to measure what I could and thus determine the thickness of black layer. The thicknesses of the strip will tell us about the thickness of the blood channel

• white part is 0.36mm
• the clear base is 0.35mm
• the entire width of the strip 0.89mm

and so thickness of the black strip is 0.18 mm (which is the depth of the blood channel). I could have tried to get a feeler gauge in that overhang, but did it this way instead.

Now we know that Amperometric analysis is used and (from this obscure source) know that the XS system uses a lyophilized reagent (reagent in dried form). The reactive components of this reagent consist of thromboplastin and a peptide substrate. In that above link (here again) chapter 5.3 is of relevance to the CoaguChek XS. But basically the blood needs to flow past the thromboplastin reagent and starting the process. You can see where it goes in and where it ends up in this picture of the underside.

Note that the hole allows the capillary attraction to pull the blood through (from where you placed the blood) across the chemistry, through to the area where the sensing occurs. You can see this below too.

The  hole is needed to allow the blood to flow right through this channel, and I assume that a light  shone through the hole indicates that sufficient blood has now reached the end of the channel. 

You can see clearly below that it is a hole below

So from all of this we see how the blood flows, why you need to put the blood on the top of the strip, or if you use the side (also mentioned in the documentation). From the Roche CoaguChek XS manual:

Exploring the 15 Second rule and outcomes

So, for those who are interested

however, as always I encourage people to not only adhere to that 15 second rule (and myself follow it) but to try as much as possible to treat it as a task that you do with accuracy and reproducibility. Do everything the same just like (say) you were making pottery mugs for sale.

Summary

Basically after watching those videos and reading the above you should know more about:

• how to use your CoaguChek XS device effectively 
• be in a better situation to understand why they make a lot of points again and again in the manual like 15 second rule and application of blood, and preparing your finger for getting a good blood sample
• You should also be able to dismiss any misinformation you may read on the internet (such as how the blood could coagulate clumps could and block the flow)
• from a logical perspective of how the whole system works both physically (the capillary attraction) and the way the machine knows sufficient blood is present.

Knowledge is power and freedom from the anxiety which stems from ignorance.

HTH

INR management philosophy (advice from the Stoics)

 One of the modern ways of thinking (well only for the last 10 years) is to have a target INR, and not think in ranges. I've mentioned this in other blog posts but I thought I'd do a post on what is probably the single most important thing: being regular in your management and aiming for targets. This is because if we aim at a target we aim for the center of the target and we know that while we may hit the bullseye we may not. This is of course not our intention. Anyone with any experience in shooting at targets knows we always aim at the center.

The Emperor Marcus Tullius Cicero understood this well.

He wrote:

Take the case of one whose task it is to shoot a spear or arrow straight at some target. One’s ultimate aim is to do all in one’s power to shoot straight, and the same applies with our ultimate goal. In this kind of example, it is to shoot straight that one must do all one can; none the less, it is to do all one can to accomplish the task that is really the ultimate aim. It is just the same with what we call the supreme good in life. To actually hit the target is, as we say, to be selected but not sought. (On Ends, III, 22)

This describes well the philosophy of Stoic action and serves as a good guide to the INR manager.

While the archer does everything he can to shoot accurately: his bow is well strung, his arrows are carefully chosen, he has taken full account of the prevailing wind and other variables, there are still other things which can happen.  These are the "externals," as the Stoics called them (or in modern economics externalities).

Despite all best choices, the arrow may not hit the bullseye, or even the target. This is because as soon as it leaves the bow the success of our action is no longer within our control, but instead subject to outside forces. So it is with INR management.

We can't know about the future, we can only decide what to do based on what has gone. This is why we keep good records and have tools at our disposal to guide our decision making.

rapid dust off perioperative INR management

A post on the management of Anti Coagulation Therapy (ACT) 

by 

Vitamin K Antagonist (VKA) - Warfarin

I've decided to call this the rapid Dust Off INR management procedure

because you get into the risk zone and out of the risk zone as fast and as safely possible. 

IMPORTANT NOTE: just like a real life Dust Off it is not without any risk (what is?) and comes with a need for experienced data driven handling of your INR; it is not for anyone who is not competent to do it. 
Further this process is not intended to replace what occurs when major surgery occurs in a hospital (in case that wasn't totally obvious). In a hospital situation you must submit to their care and they will manage you (which should include restoring your ACT before discharge) they will administer heparin and supply that. So, "when in Rome..." 

Background

Normally my posts are about me somehow, but this post is the work of a friend of mine who we'll call "Chuck"

About a year ago Chuck had his aortic valve replaced with a mechanical valve and began warfarin therapy. He's been an excellent manager of INR and (his words) is within range greater than 90% of the time. Yes folks that's better than clinics.

So (as eventually happens) he (like me) needed an invasive procedure where the practitioner requested that his INR be lowered to less than 1.5 for the procedure.

Now Chuck was well familiar with my perioperative management strategy for handling ACT without bridging therapy. I strongly recommend that you go over here and read about that in detail if you're not already familiar with it. The arguments and rational here depend on understanding that work.

Bridging therapy is when you 

1. cease one anticoagulant (warfarin), 
2. commence another which has a fast acting operation (heparin),
3. cease that, 
4. have the procedure
5. wait an amount of time to ensure proper coagulation has occurred (we do need this you know)
6. begin heparin and commence warfarin again
7. measure INR and cease heparin when INR is within therapeutic range

Its a pain not just because heparin is by injection, but because its often painful itself.

Rationale

People with mechanical valves require anti-coagulation therapy, and this is strictly about that specific application. Please read that again.

Chuck had read my (above mentioned) publication and felt that it could be improved upon (as indeed did I, but simply had not been sufficiently motivated to repeat it with improvements). Being a good student of his body response to warfarin (and naturally a good documenter of it) decided (emphasis), in consultation with his medical practitioner, to manage his INR down to 1.4 while not actually ceasing warfarin therapy. 

The "therapeutic window" (as its called) is the range of INR where you in your situation are at the least risk of either a clot of a bleed. This is known to be between approximately INR = 2 and INR = 4 (it depends). This information is based on this study which I recommend you read. This figure from that summarises the risk neatly with this Figure

which I have annotated to emphasise the lowest risk regions in GREEN and the highest in RED. The numbers are pretty clear, with the range 2.5 ~ 2.9 giving a statistical probablity of 2 events per 100 patient years, even moving to 4.0 ~ 4.5 is only 2.6 events per 100 patient years. That's pretty safe and that's exactly why we call it a Therapeutic Window.

So you can see that in the range of 1.5 ~1.9 is 26.6 events per patient year, which boils down to a high chance of an event within 3.8 years.

Our intention here is to do this in far less time than that, because time is the major multiplier of risk.

Method and Data presentation

Chuck took measurements at various intervals which ranged between daily and 4 times a day. This is the sort of data acquisition which you can only get if you have your own Point of Care (POC) machine.

This is the summary information:

First lets identify the annotations on the graph:

1. the procedure was on the 15th (black lines in the dose bar chart item)
2. a red line has been added between INR 2 and 1.8 to show we are now in the hazard zone

As there was more than one dosage and more than one INR reading for some of the days I have aggregated these and taken the INR as the last INR presenting on a day and the total warfarin taken in that day as an aggregate number. The fuller presentation of data is in this chart;

This is a little more complicated, but when referring to that earlier chart. I'll leave it to the reader to read the graph.

 

Observations

This method enabled a a time outside the therapeutic window of just 3 days (with the 12th and 16th back within the therapeutic window. This is by any way of looking at it an excellent result.

One of the biggest issues is running out of the "antagonism cycle" where the following parts of the quite complex coagulation cascade are interfered with:

• cofactors (II, VII, IV, X)
• protein C
• protein S

The details of which the reader should look up if interested. However the point is that not only does it take time to build the right warfarin levels after you have ceased warfarin, the INR being 1 does not tell you about the levels of warfarin, but only about the levels these various factors. 

By not dropping below INR 1.4 we have left the engine idling as it were. While this "engine" at idle does not produce significant power, it can be restarted again much faster. So we can be sure that some of this mechanism of antagonism of coagulation is still in place and by increasing dose we can restore the desired level of antagonism: we do not need to commence all this again from scratch.

The how and the specifics of the dose that's been used is a criteria for each person, to properly determine this you need to build up a knowledge of how your INR behaves with respect to changes in dose and changes in other factors (such as alcohol or foods). This is something that an experienced self manager will have because they have been managing themselves through a variety of cases. Additionally this method requires a rigorous approach to taking your warfarin and documenting your doses and INR.

If you are not managing yourself then this approach will require the INR manager to familiarise themselves with your particulars (not hard to do). However the literature would suggest that no INR clinic is in a position to do this for you (given that they frequently can't keep you in range > 70% of the time), meaning its best done by a competent self manager or an experienced INR manager. I guess that you can see why its not common and you've not read of it before.

Summary

This procedure is something that an experienced self manager of INR can do. It requires the careful management down of INR to a still slightly anti-coagulated state. This then allows surgeons and practitioners to undertake a procedure in the absence of significant ACT. This results in

• achieving the goal of the procedure and 
• minimising the time out of therapeutic range and 
• not requiring the subcutaneous injection administration of a bolus of heparin; which at the very least is uncomfortable and requires greater coordination with prescriptions and then administration of those injections

Ultimately if you are a INR self manager, and in the lowest risk category (as defined in the above mentioned prior work of mine on this), then this procedure may be of value to you. It is intended only for those who are on ACT primarily due to the placement of a mechanical aortic valve and who have no history of stroke. It is my view that this method should prove a helpful tool in the management of ACT around the inevitable invasive procedures we are more likely to have as we age.

Acknowledgements

I'd like to thank Chuck for the opportunity to work with him on this experiment and the generous sharing of his data.

I hope this is of interest to fellow valvers and I encourage you to take this and the earlier article on the Perioperative Management of INR to your medical team when next you face an invasive procedure.

Epilogue

Lastly I'd like to venture something I learned a long time ago, empirical observation trumps investigation into "the why" of how things work.

Theory is when we know why something should work, but it doesn’t.

Practice is when something works, but we don’t know why. 

Here Theory and Practice meet: Nothing works and we don’t know why." 

- Unknown

I prefer to go with using what I know works even if I'm not entirely sure why.

Superglue as a wound dressing

For those of us on warfarin (and maybe some others) abrasions and mild cuts bleed like stuck pigs (as the saying goes). As I age my skin seems more inclined to be broken by impacts than at a younger ages and forearms often bear the brunt of this. The other day I caught my arm on something and opened up a wound which of course bled all over my shirt (fuck).

So after I treated the wound basically (clean, apply pressure to reduce bleeding) I mix in a drop of superglue with the fluids coming out of the wound (plasma as well as a bit of blood) and allow to dry. This is what it looked like:

The opening (a skin tear) is a bit under a cm.

The next advantage from Superglue comes the next day when it is much more stable than a scab is and even after a shower you don't need to worry about "wiping off the scab and bleeding again"

Works well and will fall off as the underlying skin exfoliates naturally.

Remember:

1. apply pressure (with a bit of absorbent paper covering the wound) first
2. when its not oozing as much (should be no more than a few minuets) apply super glod
3. DO NOT apply pressure with your finger then ... unless you want a comedy to ensue

HTH

Grapefruit and Warfarin

Basically people either like Grapefruit or don't. I'm firmly in the bank of "why would I drink something that I have to ply with so much sugar to even make it acceptable to the taste. The lovers of Grapefruit will say how its good for you, but really there is nothing in it that's not easily (and more palatably) got from somewhere else. 

Some time back I wrote a blog post which identified that taking Grapefruit interfered with most medications, warfarin being one of then. As it happens this was the first blog post I did in the INR series.

The purpose of todays blog post is to add a little more clarity to that post and explain some of what was in that podcast interview.

In that podcast Dr David Bailey mentioned in his discussion talked about enzymes in the gut and the changes of bioavailability. If you just listened to that you may be a bit confused about what's actually going on with this bitter "fruit" and warfarin because you may think to yourself

"but wait, warfarin is highly bioavailable, so how does this influence me"

and that's because there is another issue which Dr Bailey did not cover and that's enzymes in the liver. Specifically thats Cytochrome P450; which as I've discussed elsewhere essentially clears toxins out of the blood (and warfarin is actually a toxin). So the active ingredient in this nasty bitter fruit is furanocoumarins (which you can read about here) that interfere with P450. This is important because if you think about it if you put something into your body where does it go? Does it stay there or go away? Some things are used to build you (like calcium in your bones) and some things are used to fuel you (like sugars) and others are deemed bad for you by the body and are disposed of.

P450 is one of the things doing the disposing. If that disposal is blocked then the toxins build up ... 

If you're actually on any medications its pretty simple : just avoid this nasty tasting "food" because it essentially brings nothing to your table.

another example of perioperative management of INR around a small procedure

I needed to have a little surgery to remove arthritis from my toe, so this being a peripheral surgery where bleeds were less likely (because of bloodless surgery possible on peripheral limbs and thus less life threatening) I perhaps took a little slacker approach on my management of  Anti Coagulation Therapy (ACT , aka warfarin).

Its just a day after hospital, so too early to talk about outcomes, but it feels like everything went well so far.

So my plan was to replicate what I did in my previous surgical procedure (which btw has a much higher risk of fatal bleeds) but perhaps act a little more conservatively on the cessation of ACT 

My procedure was slated for PM on Friday the 16th, accordingly my plan was this:

• half dose evening (regular dose time) for evening before procedure
• no dose on the evening of the procedure (after it)
• resume dose following day (evening)

Given what I found I probably should have reviewed more closely what I identified in the previous situation and gone with zero dose the evening before as well ... perhaps half the day before that.

A few more data points before the 16th would have been good, but it would seem that my INR didn't shift much (or was higher than 3 on the 14th 15th and I didn't know) as a result of the half dose and indeed rise after surgery.

Further I'd suggest that the small rise in INR despite the significant drop in dose suggests that if I had simply continued that its possible my INR may have gone higher (to perhaps 4) in the period soon after surgery. Something best avoided. So next time (I hope not, but probably there'll be) I'll monitor daily (to get data) and reduce dose to half earlier and withhold the day before the surgery.

Either way now is still a good time to have a reduced INR during post operative healing, so I'll be steering towards INR = 2 for the next week

Perioperative Management of INR

Eventually one finds that some sort of small surgery is needed, for those of us on warfarin (perhaps after a large surgery such as a heart valve replacement) the management of INR around that is important. In my case a colonoscopy was required.

This post is about my experiences in the perioperative management of my INR around my colonoscopy and thus is here also as a guide for those who (like me) self manage.

Starting point

My Gastroenterologist requested my INR to be managed down to ≤ 1.5 pre the 'procedure', which formed the basis for this "experiment" in validating my INR management and the predictive usefulness of my simple data model for INR.

Summary position

• With good data you can manage your INR down to a suitable level for a small procedure probably without need for heparin (but be prepared for needing it)
• I have again verified my model in an actual experiment but with better data gathering than before
• I was perhaps too conservative in my management strategy (but who knows)
• the outcomes were all good
• I took a Heparin shot in the middle of the 'recovery of INR' phase (for "just in case"), pehaps it was too conservative but what the hell ... 

Premise

I manage my own INR (as you'll find on this blog for instance here). In making this a bit more predictable (rather than just gut feel heuristic) I have developed a data model on how my INR behaves. Previous surgeries (some yars back now) have given me some data to work with, and years of managing myself has allowed me to collect and analyze response due to various "oops" events such as "I missed a dose".  This post is based on that and my reading and understanding of the literature. In particular the following article is a useful advice on exactly this topic:

found in full here. I urge you to read it.

From that article I found the following points of significance which guided my strategy:

Summary

The perioperative management of patients on long-term warfarin therapy poses particular problems. This situation is exacerbated by the absence of randomised trials. The strategy used is based on the assessment of each patient's thromboembolic and bleeding risks. These determine the need for withholding warfarin and switching to heparin. Most patients having minor procedures can continue to take warfarin, provided that they are closely monitored and local measures are used to ensure adequate haemostasis

My primary take outs are highlighted but as always, read the above carefully and see it in context.

Risks of temporarily withholding warfarin 

The risks are difficult to quantify due to the lack of randomised trials examining this issue. They vary according to the indication for the warfarin therapy.

The article goes on to iterate some major risk groups:

Which in my case is the simple fact that I have a modern bileaflet mechanical aortic valve ... which puts me in about the lowest risk category ... the same may be true for you too.

Next:

Do the benefits of anticoagulation outweigh the risks?

The approach to the management of anticoagulation in patients with prosthetic valves undergoing non-cardiac surgery remains controversial. The need for perioperative anticoagulation in patients with mechanical heart valves has been questioned in a recent review. The authors argue that for every 10 000 patients with mechanical heart valves who are given perioperative intravenous heparin, three thromboembolic events are prevented at the cost of 300 major postoperative bleeding episodes

Think about those numbers the prevention of three thrombo events vs 300 major bleeds. Note "The authors" refers to the study being cited by that article. That study (referenced in their bibliography of course) is "Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997;336:1506-11." and is found here.

Now as a background, one of my friends (about the same age as me, but not on warfarin) had a colonoscopy the week before me. He had a life threatening bleed (and was taken from his home by ambulance to a local hospital then transferred to a more major hospital when they couldn't stop the bleeding.

I have also had a friend die of a GI bleed ... Clotting has a major and important role in survival.

Lastly the literature is full of examples of people who have had low INR for extended periods that have come to no harm ...

Shit like this takes a long time to form, who knows how low for how long they were. So maybe we are just too conservative? Probably that's a good research question too.


So I took my management of this from that perspective;

 IE my risk of a clot (low) vs the (higher) potential for a bleed.

Management Strategy

I decided to monitor my INR daily and to cease warfarin a day earlier than my model predicted I would need to cease to achieve the target that the Gastroenterologist had given me. I wanted to do this because I wanted to make sure that bleeding wasn't a factor.

My process was this:

• measure INR daily (in the AM, usually about 8am)
• my usual dose time is 7pm
• I recorded INR and the dose
• the graph below has INR on the LHS Y axis and dose in mg on the right axis
• the bars represent actual data and the lines part of my model
• I ceased warfarin on Sunday (I take in the PM)
• my colonoscopy was Wednesday around noon

So, lets look at the data.

As it happens my model was quite close in predicting my INR reduction (represented as Pinr 3 period moving average), which fell to below 1.5 by tuesday (as predicted by the model) as well as indicating the rise in INR (Pinr 4 period moving average).

This meant that I went into my procedure with my INR of 1.2 (measured in the AM) for a 2pm procedure. This is consistent with my goals of reduced bleeding complications but a little conservative (it was my first try) and the target could perhaps have been achieved by ceasing a day closer to the procedure.

I decided to not recommence warfarin on the evening of the procedure but wait for the next day. Again it is on this point I feel that the collected data shows that  I was a bit too conservative. I believe that I could have resumed warfarin that evening and the data shows this to be correct. Making for a reduction in days outside the therapeutic window of two days less time.
NB: from 9 days to 7 days (so far).

Due to my conservative restart my INR continued to fall on Friday (down to 1.1) and so in prudence I went to my local hospital seeking a heparin shot. I (happily) met a very good young Doctor to whom presented my INR data in support of my request for the heparin shot. He reviewed my data and was quite supportive of my approach. You see, if you're organised and detail oriented you can get support from the medical community ... even if you fall outside the box.

So I could thus have perhaps restarted a bit more aggressively, but then I was concerned about the possibility of a bleed in the period of time directly following the procedure. Perhaps more conservative but consistent with the wish to avoid a GI bleed.

The strategy I employed was (using my model) to get my warfarin levels back up to a level which would resume my anticoagulation as before the process began. I did so in a manner to avoid any over shoot "spikes" in INR (due to over dosing) while allowing the INR to climb in a manner which is reasonable. My model showed me that by day 5 (of resumption of ACT) after the  I would be coming within "safe" territory, and by day 6 I would be within my desired therapeutic range (2.0 ~ 3.0).

Knowing this "delay in INR restart" I could safely shave another day off by resuming directly in the PM of the evening after the procedure, and perhaps with a larger bolus dose to start me off. This would result in an overall reduction of 1 days outside the therapeutic range making it 6 days in all.

Discussion

This process has enabled me to feel much more comfortable in managing my INR and has given me added validation that my (albeit simple) model of INR behaviour in my system works. Certainly there are parameters which need better tuning, but in terms of Pareto Principle we have 80% of the benefits here already.

Based on my model I feel that I could have reduced my window of withholding my warfarin by ceasing later and resuming later. This would have still had my INR at less than 1.5 for the procedure and raising to INR >2 sooner. By ceasing as soon as I did it allowed my INR to drop further than needed and take longer to then recover the desired levels.

However is this result bad? No, I don't think so. For the need of coagulation in my GI tract is not known, meaning it may be that I benefited from the extra time to heal. So for the sake of a single heparin shot two days after my procedure (on Friday, restoring AC levels required and perhaps also washing out / allow the destruction of any early stage thrombosis) I was able to give good coagulation to the site of injury (some polyps were removed) and act in a prudent manner.

Lastly my model has given me something important; Quantative  INR recovery estimates. This is a good source of confidence. We rely on "knowing" the future to feel less anxious about things. Knowing nothing is what you do when you gamble, knowing something can take much of the anxiety out of things and helps plan.

Much of the operation of my model is not clarified here in this blog post. That is deliberate, for until I decide what to do with my intellectual property I'd like to keep the cards close to my chest. The accuracy of the model after reaching INR 1.5 seems to be wanting. I believe this is because there are "lags in the system" which means that the INR response to the warfarin may be delayed. I normally factor in a 4 day rolling average to the model to predict the rise. As you can see it is close to that, but not perfect ... meaning there are some more research questions arising from this research.

I hope this has been of benefit to some of you.

If you are a valver, and want to work with me on your INR management please feel free to comment with your email address. Comments are moderated and I will not publish a comment with an email address.

I won't charge you anything for my assistance but I will require you work in a rigorous manner in collecting data, and taking your warfarin. I will also need a base data set of some months of weekly INR readings to build your data model from. Without all of that ... it just can't happen.

Last but not least:

Acknowledgements

I would like to take the opportunity to thank my Gastroenterologist for her great team and well executed event. Everyone was professional, caring and understanding. Asked good questions and gently demanded good answers. Everything went well from the admission through to the recovery.

Thanks Olga (you know who you are).

Also I would like to thank Michele for her kind donation of some XS strips which has saved me about $100 in this instance (cos INR tests aren't free) and will in all likelihood give me another 6 months of tests too. {HatTip}

Thanks Michele, much appreciated!

Warning

This post contains what to the best of my knowledge is the current best practice. It is good advice if you don't have any other issues that are unknown to me. As long as you measure and follow the INR levels in here I believe that you'll be fine. Indeed if I were doing it again (which unless I die soon I will be) I'll probably just restart warfarin directly after the procedure and trust my knowledge of the INR fall and go off earlier.

BUT: Don't fuck with this stuff if you don't have a clue. You may get hurt, and that hurt may be permanent. Instead get a clue and start by having a read my other posts on INR management (use the INR tag in the tag list) keeping records and being on top of your own health. Reach out to me for assistance if you wish.

2016 INR data

Well, the last measurement for 2016 has come and gone so I thought I'd put up a post with an evaluation of that (for those who are interested in my findings on Life on Warfarin).

its been a pretty busy year with house removations, and then sales, and then moving to Finland all bundled into September, October. I've re-settled into life in Finland (as you'll see in earlier posts) and have been getting into cross country skiing and training most days.

As always the graph axes are INR (LHS) , dose (in mg per day on RHS) and the scale being the numbers of the week. There is a -1 and 0 because I provide a context from the previous year.

The usual seemingly cyclic ups and downs and a little "guidance" needed in the first 3/4's of the year. But despite a bit of a bumpy ride (for the dose line, for me I was fine) I managed to keep my stats looking good. For my own purposes I calculate an INR OVER event as INR > 3.2 and an UNDER event as < 2 So with that counting arrangement I was in range 94% of the time, a pretty good result by anyone's standards (and better than many clinics).

average	2.6
std dev	0.4
max	3.5
min	2.0
over event	3
under event	0
inRange %	94.6

I did notice that the last few weeks has shown a much reduced variance in INR which seems to coincide with being in Finland. I can't think of much else to clarify it as I drink about the same amount of beer per day and eat pretty much the same ... dunno. Either way my approach takes all these variations in stride and I'm pretty sure that if I was being managed (or should that be mis-managed) by a clinic (testing bi-weekly or worse) I'd be all over the joint and perhaps have been injured by it.

My range of 2 ~ 3 as mentioned above is even a bit conservative when dealing with the high end as the literature shows that I can go higher into the 4's without stressing about bleed even risk much.

(detailed article here)

However I've found that INR > 3 makes brusing more annoying (and I was using hammer and power tools a lot till just recently) and so I keep it a bit tighter than is perhaps essential for good health.

Basically its all been good, and my regime of weekly checking and my strategy of dealing with dose changes is working well.

Happy New Year to you all

PS as some people may not be good at reading graphs I thought I'd take a moment to assist in walking through the above two graphs and explaining a little. Firstly the INR vs Incident graph above shows its safest point when the INR is between 2 and 4.5

One can see that reading my INR graph that my INR was between 2 and 3 almost all of the time. Lets clarify that with just looking at the INR plot per week:

so, lets grab that graph (which has INR on its Y axis and put that over the graph that has safety vs INR with INR over the X axis

I've also "mirrored it" to get High on the right and low on the left (just as in the safety graph),
so you can see clearly that my INR range has not strayed into the "risky areas" at all.

:-)

managing my INR - an example

Well the last few weeks has been a good example of how I manage my INR my self. Obviously the "plain sailing" is easy ...

1. dish out your pills, 
2. double check you have the exact correct dose
3. load them into your daily box
4. take them each day at the same time

its only when things go 'unaccording to plan' that management of your dose is needed. Such an event came a few weeks ago and now that I'm back on an even level again I thought I'd write this up to assist anyone home managing and self testing to see how I did it (and perhaps include of few of my methods into yours).

This post is an example of the practices I outline in my other blog post about managing INR over here. Central to that is the philosophy of "keep a steady hand on the tiller" : this means don't be micro managing adjusting (tinkering all the time) and don't be adjusting too much (meaning the dose size change). To quote from there some relevant points:

• keep your doses steady, by this I mean take (as close as reasonably possible) the same number of mg per day. I feel there is evidence to support that alternating high / low doses lead to increasing instability
• there is a natural swing in range of INR which will occur even with the same dose. Accept this and don't try to micro-manage it
• measure frequently (like weekly or fortnightly not monthly or bi-monthly)
• if there is a trend which worries you, measure more often (such as again in 3 days) to see if the trend is continuing or returning of its own accord (it may well just do that)
• adjust doses in small amounts, such as 0.5mg per day.

So this is an example of what happens when I do a mid week measurement based on an INR which I feel warrants it.

I do my testing every Saturday morning, and write this into a spreadsheet, write in my intended dose for the week and move on.

So I found the other Saturday (12 Sept 2015) that my INR had risen from 2.8 to 3.8 since the last check. My preferred range is between 2 and 3 (although in practice I don't really care if it dips a little either side of this.

The Y axis scale of my graph is omitted to keep the image compact, but the X axis represents week number starting on the first Sat of Jan.

So the red arrow points to the 3.8 reading, the dose line (red dotted line) has been consistent at 7.25mg for weeks. The lows in that graph are around 2.1 and the highs are about 3, so you can see that its "normal" for me to bounce around within my range.

You can see a few more readings following, which break out of that "stasis" that I'll go into now. The reading of 3.8 on the 12th was a signal to begin what I call an Adhoc monitor, where I increase the INR tests from weekly to twice a week. When I see something high like this, I like to follow it and see within a few days (like 3 or 4) if its going to return lower on its own ... most often this is exactly what happens.

Mostly no change is needed and it corrects itself. This is the best option ... leave it alone if you don't need to change it.

However since this occasion was nearly 4 I thought I'd also drop only my next day dose to 6 from 7.25 and check again on Tuesday. The logic of a single dose reduction is that it will have a quick effect on reducing your INR, it will then resume back to where it was going to "level out to".

Of course this is where you ignore the conventional "knowledge" that INR does not respond fast, as that is wrong.

This graph below shows the progression from the 5th of September (INR = 2.8) through my AdHoc monitor. It shows the dose in mg on the right hand Y axis (as a red dotted line) and the INR on the left hand X axis (as columns).

After my dose reduction my INR moved back to 3.2 (still higher than I wish). Note that I did not alter anything again yet. But by the next Saturday had gone back up to 3.7 again. Clearly this wasn't going to be returning any time soon, so it time to take a little bit of action

Action

From this I decided that something more consistent had changed with my metabolism so I thought I'd drop my dose on that Saturday to 4.5mg and continue at 6mg for the time being and continue my adhoc frequent measurements. Of course I also wrote the Saturdays into my normal sheet (and you can see that in the first figure above where there are 2 high readings).

The following measurements were trending in the right direction (under 3) which you can see above in the graph (if you weren't taught graphs at school I encourage you strongly to learn to read them, its not hard children do it). However the trend down started to head too low and so when on the 3rd of October I got a 1.9 I decided that I'd revise my daily dose up a smidge to 7 daily and see if that found a better balance. You can see that it did.

Outcomes

So you can see  that I've now changed my dose from 7.25mg (administered as 7.0 alternating with 7.5) to 7.0 daily and my INR is now meandering around the 2.4 area, which is (to quote Goldilocks) just right.

So looking at the second chart again:

we can see (starting at the left) that my INR bounds were creeping up to be between 2.8 and 3.8 ... my adjustment down corrected that, but to my mind it was still sloping down (the green line) and so I stepped my dose up a bit. I moved it to less than it was before, but still up by a little more than 10%. That's not a rule, its just a guide.

To my mind something seemed to happen to my body during this period and without action my INR may have been between 4 and 5 which is higher than I would be comfortable with. If one was measuring once per month it is easy to see that you could have measured 2.8 and then been over 4 for weeks without knowing it.

This is exactly why I advocate for weekly measurements, and if you are self managing then increasing your measurements in the face of events so that you can learn - but you must be structured and documented or you're just wasting money on strips.

Its also worth mentioning that this is exactly what INR clinics do. They

1. look at the measurements
2. Determine a trend
3. Adjust dose as required

They do not have any more magic than that. But unlike you they don't really get to know you. Which is why they may make more changes than you would. Wouldn't you be happier with an extra finger prick than an extra vein draw to get this data? I know I am.

This is also a good example of why you don't use massive variations in dose, such as  5mg one day, and 10mg on another day. There is just no way you can expect to ever be stable or reliable with such input variations.

So now

• my INR is now exactly where I want it to be
• my INR did not stay too high or too low during the adjustment period
• I have found and established a new stable dose

No problems, no "bleed events", no bruises (even though I was working on my motor bike engine and bashed myself many times) ... all because I was monitoring and adjusting with care , caution and diligence.

I hope this helps you to do the same

:-)

POST SCRIPT

It is now Saturday the 24th of October and my INR reading this morning was 2.2 with a weekly dose of now 7mg shown above. I seem to have gone back to my normal metabolism again, so I'll resume my 7.25mg per day dose that I was previously on.

This of course begs the question of "should I have done nothing" and "was there any point in knowing".

My answer is this: If I had done nothing my INR could have remained above 4 for a few weeks. This is not in itself a significant problem. But if I'd had an accident (say a motorcycle or car crash) it could have exacerbated any inter-cranial bleeding and thus brain damage.

Its true that mostly we don't have accidents, but do you wear your seatbelt most of the time? If you do then you'll know that wearing it only matters if you have an accident.

Thus I like to keep my INR below 3 most of the time.

Just be sure that you don't over manage it, look for trends and adjust in small increments.

In hindsight I think that dropping my dose to 6mg daily after I took action on the 19th was perhaps lower than I should have done for the smoothest possible outcomes. Next time I'll drop it to 6.5mg instead. Of course there was nothing "wrong" with being between 1.9 (the lowest recording) and 2.3 ... its a good result too.

Best Wishes

Managing my INR (some practical tips observations and theories)

A patients perspective

I've decided to put this page together because on looking around the internet I see heaps of rubbish, mis-information and myth out there for people who are on warfarin as an anticoagulant.

Firstly - the good news

I wanted to say that managing my INR myself is incredibly simple and takes me about 5 minutes per week. Learning to use an INR monitoring machine is dead simple (a quick video provided) and (almost) any idiot can do it. If you buy strips online they cost so little that if you are an able bodied person you just couldn't consider doing it any other way.

By using the Coaguchek XS I have been essentially free to travel as I wish (moved from Australia for a year in Finland, traveled to the UK and other places) and more or less unbound in any way by being on anticoagulants.

As a bonus its been really cheap, with tests costing me less than $6 per test.

In this post my main focus is on those of us who are on anti-coagulants for the fact that we have a mechanical heart valve. As I understand it there are quite a few out there who simply do not monitor their INR after their heart valve replacement, and perhaps bumble along with a fixed dose and no idea if its good or bad.

So my Valve Brothers and Sisters if you are still reading its all good news. I encourage you to go to eBay and buy a Coaguchek XS (or simmilar) get online for strips and look after your health, for your self by yourself!

In a nut shell what I do is:

1. sample my blood to determine my INR
2. write that down (spread sheet, but book works)
3. determine if its been over time falling or rising (a graph on a SS really helps)
4. make a small adjustment to my dose if needed to correct for my INR falling or rising (usually adjustment isn't needed and its better to leave it alone, more later)

That's it ... compared to a diabetic, life on warfarin is really simple.

Looking at the research, by following good practices (simple really) you can make life on warfarin much safer than the stats that are usually presented. Point of Care machines (like my Coaguchek) make dosing warfarin both accurate and convenient.

The rest of this post is really just here to explain more details and provide a basis for my view.

In this post I will refer to warfarin as the name of the chemical substance we take. So for those (Americans usually) who can only think in terms of product names and refer to this as  Coumadin (which is actually a product name of one company) you can be clear that I am not talking about any product in particular. Calling it coumadin all the time is like saying you have a Hover instead of saying you have a vacuum cleaner when you actually own an Electrolux. I use the product called Marevan , but its unimportant to the discussion.

I thought I should also say up front that my view is that : Everything I know is subject to change based on more information. The more I learn the more I tune what I understand and how I see what I know as meaning.

I have my INR target determined by my condition, which is that I have a modern pyrolytic carbon mechanical valve. If you have other reasons for being on anticoagulants then consult with your physician as to what your target INR is and then apply that to the information below.

So, why is this here?

Essentially I was a annoyed with my INR monitoring clinic. I saw that it was essential for me to have started with them however I out grew wanting to be managed for reasons such as:

1. I didn't want to be fronting up for a vein blood draw fortnightly, often weekly and sometimes twice a week. It was inconvenient (as I have to go to work) and uncomfortable (as sometimes they had trouble getting blood)
2. I wanted the absolute best for my health, and I became certain that only I was sufficiently motivated about things to ensure that
3. I learned enough to realize I could do it better than the clinic and for less money and for less hassle

I believe strongly that for those of us who are on warfarin for no other reason than because we have a mechanical valve, life really can be safer than if you took the tissue option to avoid what the doctors drummed up as the horror of anticoagulation therapy.

So, lets next have a ...

Quick summary

This post assumes you are already on warfarin and have been for some months. I also assume that you are not one of the small percentage of people who are having difficulties with it or having compounding problems with being on other drugs. I hope that after reading this you can stabilise your dose and stabilise your INR and reduce any possible complications ...

So this in this post I say:

• keep your doses steady, by this I mean take the same number mg per day. I feel there is evidence to support that alternating high / low doses lead to increasing instability
• there is a natural swing in range of INR which will occur even with the same dose. Accept this and don't try to micro-manage it
• I have learned that nothing is fool proof because the simpler you make things the more you encourage people to be stupid. So if you can't do maths or work with numbers (like what's half of 5 + 5)  and are currently with an INR management clinic, then stay with the clinic (even if you're unhappy) and just bitch about the mistakes they make (and the frustration they cause). Be comfortable in the knowledge that you'll make worse ones if you manage yourself and can't do numbers yourself.
• measure your INR consistently, getting a good sample helps (I show a video of a method I use) as does consistency of technique.
• there are many myths about INR which lead you to make wrong assumptions (and I attempt to demonstrate this with some facts), these myths perpetuate due to simplifications (aka dumbing down) and extrapolations from those simplifications.
• measure frequently (like weekly or fortnightly)
• if there is a trend which worries you, measure more often (such as again in a 3 days) to see if the trend is continuing or returning of its own accord (it may well just do that)
• adjust doses in small amounts, such as 0.5mg per day.
• split pills not average irregular doses
• don't think in weekly doses, think in daily doses

If some of these points seem serious - well that's because this is a serious matter. You can do yourself harm with this if you are not careful. Equally if you are on anticoagulants and are testing infrequently (I've heard of people testing every few months!!) you can do harm too, so go get a machine ASAP and start taking better care of yourself.

What is INR anyway?

Well INR stands for International Normalized Ratio. Wikipedia has a good summary here. Reading that one can see it boils down to a ratio (you know, like 1 over 2 is a ratio) with my clotting time (which will be longer) over the "normal" clotting time. This is of course slightly crazy as what is a "normal clotting time" ... would there not be variation in times among people?

The answer is of course yes (and the details are there to be found for anyone who is interested enough to read). But for people uninterested in details I bring this up because I wish to stress a significant point:

THIS IS NOT AN EXACT SCIENCE AND THERE ARE RUBBERY EDGES TO EVERY ASPECT OF IT - SO DO NOT FRET OR OBSESS ABOUT FRACTIONS OF DECIMAL POINT.


Ok, with that (important) point out of the way lets move on... Clearly the first point in working out your INR is...

Getting Blood

Perhaps obviously when managing your INR one of the first things you need to do is get blood, to see how fast it clots. There are more or less two ways:

1.  the labs (which means you aren't managing your INR) use a needle and a syringe. Personally I'm no fan of "the jab" as I've had more than my fair share over (most of) my life and also only have an easy vein on my left arm. This results in frequent annoyance.
2. a (finger) pin prick and use of a Point Of Care machine. This is actually becoming more common (even in hospitals) in the medical world as people begin to grasp that the devices are both sufficiently accurate and cost effective to run

Naturally I use the finger pin prick POC device, as the idea of stabbing myself with a longer needle and sucking blood is not appealing.

So when doing this you need to follow the instructions of the device. I happen to use a Roche Coaguchek XS and it specifies 8µL or "a full haning drop". Actually getting enough blood is often not as easy as it sounds. Sure you can just give yourself a good scratch and get it, but if you do this frequently (I'll get onto that in a minute) its annoying to have what amounts to a permanent small injury on one of your fingers.

So, firstly on some mornings (I happen to test on Saturday mornings as my routine) I sometimes had trouble getting a good blood sample and would get the annoying "Error 5" displayed. This means you didn't get enough blood into the test strip and you'll have to toss the strip and try again. At $5 a hit its a slightly annoying thing to have happen ... it gets more annoying when you've blown two strips to finally get a reading with the third (meaning you've just cost $15 to check your INR).

My method is to lightly wrap a small rubber band (which I've cut to make it a small rubber strap) around my finger to act as a pressure bandage and to restrict the blood flow back up the vascular system. This means I can regularly get a reliable sized blood sample and (perhaps importantly) stay within the strict guidelines of Roche on the maximum permissible time that can pass between lancing and application (supposed to be 15 seconds, which I think is actually baseless, but that's a different post). From the Roche Coagucheck manual...

So now you know if you didn't before ...

Anyway my sample method is described in this video:




So as you can see, my method assures that:

• that you get more than enough for a good sample (and to avoid Error 5 and wasting a strip)
• do everything consistently and repeatably
• avoid milking the finger excessively (something mentioned in the manual as a no no)
• minimise the lance injury (who likes ongoing discomfort?)
• follow the 15 second rule (and preferably keep time between "ready beep" and application of blood consistent too)

Indeed using this system the time from starting my pressure bandage (and remember, you're not aiming to cut your finger off, just restrict blood flow, so don't wind that band on too tight) to getting a sample on the strip is repeatably less than 15 seconds. Which of course means that there is minimal time for anything metabolic to occur.

Finally I would encourage everyone who is starting out taking their own INR to compare their results to a lab draw (and please, do keep which lab you go to consistent, as there is significant interlab variation). If you compare your samples to a lab make sure you always follow the same procedure, as variations of your procedure may also influence your results. When I first started I was often up to 0.8 units away from my lab. Once I'd standardised my approach I was down to less then 0.3 (which is not significant really).

Sidebar: a quick comment about lancing, always lance the side. There are a few reasons for the choosing the side:

• ask a diabetic, over time pricking the same place you damage the nerves, doing the side minimises the effect of that
• it hurts less
• the skin is thinner and so the lance does not need to be as deep
• if you need to do work later it won't be as annoying there as a finger tip

So using the methods above you can get good consistent readings of your INR and not waste strips. Which then brings us on to the way that you achieve your target INR, that is...

Dosing

In this post I will assume that you are already started on warfarin and have something like a stable dose (I'll discuss stable in a tic). Starting warfarin is a critical time and frequent monitoring needs to take place to ensure no problems arise and to work out your sensitivity to warfarin. Actually blood tests exist for this, and are helpful in identifying thegenes of those who need significantly lower doses. To my knowledge this is seldom done. However I digress.

Being stable on warfarin essentially means that you have an INR somewhere between 1.9 and 4, even if that wanders around from time to time. I hope that by reading this post that you may be able to make some changes to how you do things and your INR fluctuations may actually reduce. In my view it would seem that to some extent achieving INR stability is made more exasperating by those who manage INR. I will present here some of what I've found and hope that it helps you.

Essentially I dose myself these days, but some people may just do their own testing, and call that into a lab or clinic who manages your dose for your (aka: tells you what to do). Personally I've found that to be a headache, although less so than when they were drawing blood and managing my INR. The reasons for this are many fold; everything from the hassle of getting in during hours I needed to be working, weird dosing advice through to overzealous micro-management of my dose and attempting to steer it.

At the end of the day you really just don't know who's at the clinic, who's keeping track of your data, what their view of this is, what dosing strategy they use, if they know diddley about it. To this end I took over my own dosing about a year after getting my mechanical Aortic valve. To be honest since then I've learned heaps and my INR is much more stable.

NOTE: I believe that if you are going to do your own dosing then you must be of the mindset to be competent to do so, be rigorous in what you do and be willing to take responsibility for yourself. If you do not feel this way, then I strongly recommend you stay under someone elses care and be a passive recipient. To me this equates to being a victim instead of in control.

So first let me present my 2013 data and I'll use that to discuss a few points. Note that each data point represents one week. If I was testing monthly (or bi-monthly as some do) I would not even see these variations. So while extra data helps to see things its important to not over react to it.




On this chart I have my INR (in blue, with the values in blue on the LHS) and my dose in mg of warfarin. There is also a red "moving average" of my INR in there too which I'll explain in a moment.

I guess that you'll  perhaps see that its not "rock steady", however it sits nicely within a range of (for that period) no more than 3.4 and no less than 1.9 ... this is a pretty good range actually. This result gives me:

1. an average of 2.5
2. a standard deviation of 0.3
3. and a score of 91% of being inside my range

91% inside range is better than most clinics obtain.

I think its important to point out the language used by clinics and the misunderstanding of that by the public: when the clinics say "stable INR" they don't mean flatline (only dead people have totally steady metabolisms), essentially nobody has a "stable" INR. Rather people have INR's which will remain within a range for a given dose. Please refer to my page "the Goldilocks Dose" for a discussion of mine.

As you can see, I do make small changes to my dose, but only when I see that it is trending up or trending down. This is the reason for my having that moving average: it helps me to see this trend (in conjunction with looking at the raw data graph too). This change in trend indicates a shift in metabolism (perhaps caused by diet, perhaps by health ... it doesn't matter), and you can then re-position your dose by a small amount to optimize your outcome.


Some important points emerge from a closer look at the graph too. For instance in the earlier part of the year I was in hospital to have some surgery, there they managed my dose and took me off warfarin for a few days for the surgery. You can see that my dose went down substantially (soon to be followed by my INR). I increased my dose (from 6 to 7mg) and my INR responded rapidly. It fell a little and I thought I should increase my dose by much less at this point) and it rose again. Anyway, you can see the see saw effect happening, frequent dose changes, rapid and significant INR swings. From this I could see the significance of small changes in my dose and developed the view that: make dose changes small.

From then on you can see that my dose changes were small, in the order of ¼ a mg per day (yes, that's right I was splitting a 1mg tablet into 4 and putting that with my 7.5mg to make it 7.75mg per day). As to why I go to such lengths of consistency is because I believe that consistency is key to this.

myths

I find it interesting that people believe ideas which are mutually inconsistent. For example:

1. INR takes days to show the effect of a dose change
2. skipping a dose will be a big problem (and why would that be if INR takes days to be effected?)
3. you can work out a weekly average dose and then divide your tablets across that (so 10mg one day, 5mg the next, or something like that)

Now let me say that I am not going to flatout disagree with these, but to make clear that they are simplifications. Simplifications have a role to play in our lives, from making communication clearer through to helping us make sense of the complicated. They should not be used to make decisions or predictions.

So it is in making dose adjustments using these simplifications as a basis where we cause problems

Now (being an engineer and a biochemist based science trained person) I naturally wanted to understand if there was anything that could assist me to model my INR and make predictions. That is after all why science has got us to where we are rather than witch-craft or entrail gazing. As I had been observing my data (gathered from weekly testing) I was of the view that some patterns were emerging. What I needed next was some good experimental data...

Experimental Data

Lets look at a some data that I actually took just before I went into hospital. I knew that I was going to be off warfarin for a few days during my stay (turned out that I was off warfarin for 3 days), so it provided a good opportunity to use myself as an experiment. I like graphs, as they are a really handy way to represent numbers. If you are at a point in your life where you can't manage numbers or understand them then I urge you to not manage your own INR.

My actual measured INR had a gap in it because (variously) I was in surgery, then in ICU then unable to get my hands on the data from the hospital. So I do not have a reading for some days, thus you will find a discontinuity of the Measured INR. The green line was what I initially developed for my rudimentary mathematical model of how INR may behave.

The model of INR was based on nothing more than knowledge of the half life of warfarin in the body and applying general principles to it. It is not based on measurements actually got from me (which would be bloody nice to have mind you). In general warfarin is removed by our bodies at such a rate that half of what was put in is removed over 2 days: that is to say it has a half life of about 2 days. Obviously each person is different (based on well known genetic parameters actually) and each person will have variation depending on a number of factors (health, other drugs ...). Since you take an amount of the drug every day your level of warfarin in your system is a combination of what you just took, what was left over from yesterday, the day before and so on ... so for a 7mg dose this would be something like:

7.00, then 12.25, then 15.75, then 17.85 and stabilising at 19.60

Then I've simply applied a fixed scalar multiplier to the accumulated amount. This is of course assuming that the INR response to warfarin is linear (which perhaps in part of the curve it will be). So its a rubbery model, but better than nothing.

Looking at the graph you can see that green line sank to an INR of barely above 0.5 (which is probably illogical as it will not make my blood clot faster, although that's an interesting question in itself), however (of course) the trend line didn't sink as far (sinking to an INR of 1). I have found that the moving average is a helpful tool as it essentially adds simple buffering to the system (which it may in practice have).

When both my dose and then testing did resume the INR which was measured was actually quite close to the model, somewhere between the Moving Average and the Predicted INR. That it did not rise as fast as the others did, could be attributed to (for instance) a lack of responce to the 1mg increase in dose for two days. None the less it was continuing to rise where the model plateaued out.

This makes it clear that my INR dropped rapidly upon stopping the dose (which would seem obvious) which counters the "myth" that it takes days to see any change in the INR. Its a real pitty I didn't have opportunity to measure it for the whole time. For obvious reasons I'm unwilling to go off for 3 days just for data gathering. (I know, I know, where's the commitment...)

Subsequently to this I've missed a dose by accident (and more than once I may add) and have then taken readings to see what has happened. My (sorry to say) many observations of missing a dose and taking taking daily INR readings have shown that the response of INR to change in my warfarin level is surprisingly rapid.

Thus further nailing down the coffin lid of "it takes days to see any change".

So lets examine the "alternating dose" strategy briefly in this light. As we've seen INR does vary somewhat even day by day it can be observed. People look at their calendar or pill boxes (a physical version of a calendar BTW) and think, "oh well I'll just alternate my does 10mg and 7.5 mg" (I assume such alternation is because in the USA Coumadin is commonly found in doses which includ 7.5mg and 10mg

This makes sense because medical people know that most of the general public can't be trusted with numbers (return again to my advise above for the numerically challenged) and so basic arithmetic is out of the question. Combined with the fact that few people want to have more than 2 pill sized on hand and are likely to get them confused anyway (again, I refer to my numeric advise above).

They would think that their strategy of alternating doses of 10 and 7.5mg would give a value of 8.75mg per day on average ... sadly it doesn't, but I'll get to that.

So taking this alternating dose you will likely see warfarin values (and hence probably INR values) following something like the pattern in my simple mathematical model

Which shows an average dose of 8.75 *(the orange linear trendline) and an INR potential varying between 3.4 and 3.6 ... so think kid bouncing up and down on a trampoline ... you know, simple harmonic motion.

However firstly its not that simple because you probably are taking your 10mg dose on Sunday and Saturday as shown in the above graph ... of course we all know that the weeks run into each other, so that means that on Monday you've really had the dose of 10 and 10 added ... so it will actually look like this:

Notice that now after Sunday we've got a significant extra bump in it? The modelled INR line now looks far less even doesn't it...

In fact the average is now 9 not 8.75 when we consider the entire period and the overlap of the weekly roll around from Saturday to Sunday ... To do proper alternating dose you'll need to switch your starting day in your pill box from 7.5 to 10 each week, and remember that ... suddenly its not as simple as it sounds and just keeping it "steady as she goes" with a daily dose which is the same or very close to it is looking better. ... if you can add up and divide.

I'd also say this makes the other myth of taking irregular doses and averaging across the week will be OK to be another bad idea, probably based on a simplification that the response to INR is not seen within a week.

Sure, if you really want to do it then fine, however if you have occasional high spikes of INR and a bleed event don't say I didn't give you the reasons for that.

Going back for a minute to my earlier (weekly sample) years chart we can see how on occasions small dose changes occasionally resulted in rather large spikes in my measured INR? I have the view (and I've been working on the data to support this view for some time now) that such is caused by the addition of other metabolic influences which combine to push INR high. The more things that are influences the more that the situation could occur that the INR be flung even higher due to a synergy of events.

Simple harmonic motion is just up and down, but when you add another influence things get difficult to predict. Try bouncing on a trampoline with someone else. Simple harmonic motion becomes more complex.

You may not bounce as high, or you may be flung off.


You may not think that the bounce in INR is created by the bounce in the residual levels but I see evidence that it is. I've discussed above, with a number of pathologists and even endocrinologists. However despite this I have read some idiots (clinics) giving instructions to patients for even greater variance over even greater spacings: such as alternating doses of 7 and 12 or 10mg twice a week and 6mg the other days.


God only knows what will be the outcome of that one but I doubt it's stability.

As I pointed out in my other post (see post The Goldilocks Dose), I have found that even on a dead steady dose my body has variations (bounces or oscillations) in INR even when I have a continuous regular daily dose:

dose mg	7	7.5	8	8.4
MAX INR	3.19	3.14	3.64	3.87
Average INR	2.43	2.60	2.77	2.95
MIN INR	1.82	1.95	2.08	2.21

So if someone was attempting to micro manage the INR which was falling or rising based on some other cycles (and look again at the graph above to see the times when there was variation but no dose change) it could make you even more unstable. Keep a steady hand on the tiller.

When it comes to INR range and the health issues with being too low or too high, a great resource is a study which has covered some thousands of patients and documented INR and "events". The important chart (for those of us with mechanical Aortic valves) is this one (article here)

Which shows that between 2.0 and 3.5 the number of "events" (you know, bleeds, thrombosis ... the usual stuff) is really low. Either side of that and the numbers step up. This feeds into my strategy, helping me set my bounds. Interestingly my surgeon initially recommended a range of 2.2 ~ 3 ... which sits well with the above findings...

my strategy

I aim for a target of 2.5 (which btw is the recommendation of the European Society of Cardiology for a mechanical Aortic valve, if you have a different valve you should follow the recommendations for your valve). I try to keep my variations in INR small, but know that fiddling will likely set up see saw events (making things wose). Thus I only alter dose if things are trending out of range. As I mentioned my average is 2.5 (bang on target) and my standard deviation is 0.3 ... which means that mostly I'm somewhere between 2.2 and 2.8 (if you didn't know what a standard deviation is).

So now that I have set you up with much of my reasoning, I can say that basically my strategy is this:

• keep the doses regular (same dose each day)
• do not adjust dose unless you see a consistent trend down to a minimum bounds
• even then stay your hand till you know more. (I increase measurement to twice per week, this allows me to see if its sinking more still or rebounding to within bounds again)

I normally measure weekly and when I see my INR going out of bounds I do what I call an "ad hoc" measurement where I measure again on Wednesday (recalling that I measure on Saturday). This gives me the extra information to see if INR is still going low/high or has stabilised (and thus likely to return on its own).


I know that dose adjustments can set up see saw responces, so I try to alter my dose infrequently. You can see it sitting at the same level for weeks at a time in the graph above, with often only 0.25mg variations when I do change it.


I encourage you to (after reading this) again read my post on The Goldilocks Dose and review this in the light of the above some of the points I made in there. I think these two article go hand in glove, but can't work out which should be first. Specifically the points about cycles which seem to occur which result in the INR changing for the same daily dose. Also consider the idea that one can find a comfortable dose which fits within a safe range. However (as identified in that article) its possible that the natural variations may take you outside of the zone ideal zone. Naturally regular testing makes it clearer what is happening and helps you stay within range (a good thing).


At the end of the day one could take the view that I could have just sat on a dose of 7.5mg per day and been done with it. However its clear from the data that there were times when I'd have had an INR of probably close to 4 or perhaps more. If I had allowed that to happen it would actually be risky in terms of a bleed event (perhaps even provoked by a fall off my mountain bike).


So to me the answer is frequent monitoring.

Since the cost of a test is quite low I really don't mind making extra tests per year than work with some "theoretical minimum". I believe its always good to have more information than not enough. In fact not enough data leads to you not being able to understand why you had the problem.

I think that its perhaps a good time to talk about my little problem: I'm over analytical. Probably I record more data than is needed. Some people don't record as much as me or even do any analysis. Hell even I'm willing to concede that most of what I keep is only of benefit when making analysis. My Coaguchek XS stores the last 100 or so readings anyway, so if I wanted to skip back through that it shows the INR and the date.

However its no harder to keep a month of readings and graph it than it is to keep all of it. I keep my records rigorously in a spread sheet (which is backed up onto dropbox for just in case) and use that data to form the basis of my analysis and learning about myself. If nothing else it has given me knowledge and has removed the anxiety of "oh sheet, I missed a dose" ... and knowing if this is a problem or not.

Understand that your body is not a static thing and that things such as starting a new sport, stopping a sport or change of diet will alter your metabolism and you'll need to check your INR. Since you're checking weekly (see my above point on frequent monitoring) you'll pick it up quick smart anyway. If reading this has helped you to understand that change a bit more then that's a good thing too :-)

Food

Have you noticed that I haven't talked about food? Well the reason is that I've found that it makes stuff all difference (unless you eat a whole case of spinach in a sitting) and if you did start get any change to your INR you'd see that in the next weeks measurement :-) If you do see anything, work out if this is important and if its actually a consistent diet change.

BTW I don't do fad diets. Instead I more or less watch what I eat ... almost all the way to my mouth so as not to get it on my shirt.

So, in short, don't stress, be happy, keep a weather eye on the horizon and a steady hand on the tiller. Make course corrections only when you are sure they're needed ... 

Hopefully all this has helped you become a better navigator of your INR

Live Long and Prosper