So You Are On Warfarin

Check out my other blog entitled "So You Are On Warfarin",

 at http://warfarininformation.blogspot.com.au/.

It covers:

• So you are on Warfarin
• What exactly is warfarin?
• How does warfarin work?
• How is your INR measured?
• How accurate are INR measurements?
• Changes in INR dosage - a warning
• What problems might you encounter on warfarin?

All good information!

Are you happy with the advice you get on changes in warfarin dose when your INR is not right?

I have some major concerns about the advice that I receive from my pathology lab when they indicate that changes to my INR are required.

My INR target range is 2.0 to 3.0. Now if you have read the 2 posts below, you will realise that the measurement of INR is not particularly precise, and that adds to the difficulty of assessing just what changes are required.

A few weeks ago, I was on a schedule of 4.5 mg and 5 my alternative days. On testing,  my INR was below 2.0, at about 1.7.The pathology lab advised that I should now take 5 mg warfarin on Sunday, Tuesday  Thursday and Saturday, and 4.5 mg on the remaining three days each week.

Now on my original schedule  I would get 7 days of 5 mg and 7 days of 4.5 mg each fortnight, making a total of  66.5 mg per fortnight, or a total of 33.25 mg/week.

On my pathology labs new schedule, I would get 4 days of 5 mg per week, and 3 days of 4.5 mg/week, or a total of 33.50 mg/week.

So, although my INR was significantly below 2.0, at 1.7, the dosage suggested increased my warfarin intake by only 0.25 mg/week, or about 0.75% !!!!

My INR of course did not shift.

Again, quite recently, my INR was 2.0, and the lab called to change my dose.

I had been on 4 mg and 4.5 mg alternate days, a total of 59.5 mg/fortnight, or 29.75 mg/week.

Their new schedule they suggested was 4 mg on Sunday, Tuesday,  Thursday and Saturday, and 4.5 mg on the remaining three days each week. This resulted in a dosage of 29.5 mg/week.

So the dosage suggested was in fact a decrease of 0.25 mg/week or about 0.75%, in spite of the fact that my INR was at the lower level recommended!!!

I rang to point this out, and they changed my dose, somewhat reluctantly, to 4.5 mg Monday to Friday and 4 mg on Saturday and Sunday. This results in a total dosage of 30.5 mg/week.

So their new recommendation was an increase of 1.0 mg/week. or 3% increase, compared to their first recommendation of a decrease of 0.25 mg/week or a decrease of 0.75%.

Clearly, I have no confidence in the information or recommendations provided by my pathology lab.

Now let's have a look at what is really required for changes in INR dosage to have a real effect. Below is part of an abstract from an article published in 2000.

Management and dosing of warfarin therapy.

 Gage BF, Fihn SD, White RH

Division of General Medical Science (BFG), Washington University School of Medicine, St. Louis, Missouri, USA.

The American Journal of Medicine [2000, 109(6):481-488]

When initiating warfarin therapy, clinicians should avoid loading doses that can raise the International Normalized Ratio (INR) excessively; instead, warfarin should be initiated with a 5-mg dose (or 2 to 4 mg in the very elderly). With a 5-mg initial dose, the INR will not rise appreciably in the first 24 hours, except in rare patients who will ultimately require a very small daily dose (0.5 to 2.0 mg). Adjusting a steady-state  warfarin dose depends on the measured INR values and clinical factors: the dose does not need to be adjusted for a single INR that is slightly out of range, and most changes should alter the total weekly dose by 5% to 20%. The INR should be monitored frequently (eg, 2 to 4 times per week) immediately after initiation of warfarin; subsequently, the interval between INR tests can be lengthened gradually (up to a maximum of 4 to 6 weeks) in patients with stable INR values. 

I have underlined the important text - most changes should alter the total weekly dose by 5 to 20%!!! What is going on with 0.75% or so advised by my lab - this would be the same effect as eating a bit more greenery in the diet!

The figures advising changes in the range 5 to 20% for useful changes in INR are supported by a number of other works.

So my advise to you, if you are on warfarin:

• ALWAYS ask for your INR when you get tested, don't just blindly accept the dosage changes recommended. 
• Keep records of your INR and dosage and dates tested
• If changes are recommended, do the arithmetic yourself, and see just how much of a change in your weekly dose  has been proposed - if it is less than 5%, ask why!

Just a bit more information supporting these recommendations from

https://www.careinternet.net/caregiver/warfarin.php

INR²	Action
>10.0	Stop warfarin. Contact patient for examination.
7.0-10.0	Stop warfarin for 2 days; decrease weekly dosage by 25% or by 1 mg/d for next week (7 mg total); repeat PT³ in 1 week.
4.5-7.0	Decrease weekly dosage by 15% or by 1 mg/d for 5 days of next week (5 mg total); repeat PT in 1 week.
3.0-4.5	Decrease weekly dosage by 10% or by 1 mg/d for 3 days of next week (3 mg total); repeat PT in 1 week.
2.0-3.0	No change.
1.5-2.0	Increase weekly dosage by 10% or by 1 mg/d for 3 days of next week (3 mg total); repeat PT in 1 week.
<1 .50=".50" td="td">	Increase weekly dose by 15% or by 1 mg/d for 5 days of next week (5 mg total); repeat PT in 1 week.

I'd suggest that ytou use these as an indication of what should be suggested by your pathology lab

How accurate are INR tests?

A really good article is available at ClotCare online resource. Much of the information on that page is reproduced below:

At ClotCare, we often get questions from people who have obtained INRs from 2 sources in a short time period and want to know which source to trust. For example, maybe the lab reports an INR of 3.5 when a point of care (fingerstick or POC) device reports an INR of 2.5. What do you do in this situation when one source indicates a high INR and one reports an INR in range?

In general, if performed correctly, the INR is usually accurate and reproducible, but there are a number of ways in which an incorrect INR can be obtained. If the INR result does not "fit" with previous values and/or what is expected, it is always reasonable to obtain another blood sample and repeat the test.

Lab reliability may differ from one lab to another: One lab (lab A) that I work with is very reliable and reproducible. For example, a few years back we had the lab perform duplicate INRs on 2 blood samples collected at the same time from a number of our warfarin-treated patients. The INR results on simultaneously collected blood samples did not differ by more than 0.1 INR units. Further, over the past 10 years we occasionally would re-test a patient with a POC device if we suspected the lab INR to be incorrect. We practically never see a substantial difference between the lab and the POC in those situations. Lastly, I have seen a number of our patients with INRs from lab A whose INR did not vary by more than 0.2 INR units over a period of several months. Therefore, I am convinced that INR results from lab A are very reliable and reproducible. On the other hand, a study that we performed in another setting using a different lab (lab B) found that approximately 10% to 15% of the INR results were wrong. 

The BOLD sentence above has been emphasised by me. It is a worry that some labs are much better than others in their reliability

What about lab vs. POC results? In general, some studies have considered INR results from 2 methods to be in reasonable agreement if the two results are within 0.5 INR units of each other (ex. 2.0 and 2.5 would be in reasonable agreement). 

We conducted 2 studies years ago to compare lab B INR with POC INR results.¹ In both studies, we did simultaneous POC and lab INRs - lab B was actually either of two labs (one at University Hospital and the other at the VA Hospital - both of which are affiliated with the UT Health Science Center in San Antonio, TX). If either method (POC or lab) told us that we needed to change the dose of warfarin in these very stable patients, we had the patients come back in 24 to 48 hours and we repeated both the POC and the lab INR; in no instance did the repeat INR results indicate that a dosage change was needed. 

Again this is not good - significantly different results and outcomes. 

After the study was completed, we evaluated "erroneous" INR pairs (simultaneously obtained POC and Lab INR results). We considered paired INR results to be "erroneous" if the POC and lab INR differed by more than 0.5 INR units and if one method or the other would have led us to make a dosage change. (Paired INRs that differed by more than 0.5 INR units were not considered "erroneous" if neither value would have led to a dosage change - an example might be paired INR results of 2.2 vs 2.8). We identified 16 erroneous pairs of INRs in study #1 and 37 erroneous pairs of INRs in study #2. Among those erroneous pairs of samples, we found that 15 of 16 in study 1 and 26 of 37 in study 2 occurred with the lab INR method. In other words, the POC results were more reproducible and less likely to result in an incorrect dosage change.

My underline emphasis above. This is a quite remarkable result, and would indicate that the lab INR methods need significant attention

My conclusion from the above studies and experience with lab A is that the POC INR results were more reliable and reproducible than those obtained from lab B; but results from lab A are just as reliable as those from the POC device.

What can cause INR results to be incorrect?

There are a number of factors that can result in a given lab INR being inaccurate. A few examples are listed below:

• Under-filling the tube when blood is collected can lead to a higher INR result
• Using a blood collection tube that contains 3.8% citrate rather than 3.2% citrate can falsely increase the INR
• Performing an INR on a blood sample of a very anemic patient (low hemoglobin and red blood cell content)
• Entering the wrong ISI (International Sensitivity Index for the thromboplastin reagent that is used in the test) into the machine
• Having the laboratory device set at an incorrect temperature
• The patient taking other medications that may alter the test
• Having an interfering substance (such as certain antibodies) in the blood

With the POC INR, since it is performed on fresh whole blood, the problems listed above that relate to blood collection are not a problem; but the other potential sources of error may be. Further, there are other factors that may lead to an error in the POC INR result. For example:

• If a patient squeezes his/her finger too hard when obtaining a drop of blood for a POC test that may accelerate the blood clotting and give an INR that is low.
• If a patient takes too much time to apply the drop of blood, clotting may start before the blood is applied to the POC test strip and than may also give an INR that low.
• It also has been suggested that heparin or low molecular weight heparin may elevate the POC INR more than the lab INR because of differences in the method and the thromboplastins being used. The POC test is performed on whole blood while the lab INR is performed on plasma that has been separated from the blood cells.
• If the POC device is not on a flat and stable surface, that too may alter the results but the degree of alteration in the INR may depend on the underlying technology of the particular POC device. For example, one device used vibrating iron particle and recorded that the blood had clotted when the particles stopped vibrating. When the device was placed on a counter that was subject to mechanical vibration from other causes, we found that the INR results were often increased due to the additional "outside" vibration.
• Improper storage of the test strips also may lead to incorrect POC INR results.
• Some POC devices require that a computer chip be changed out with each new lot of test strips, failure to do so can yield incorrect INR results.

So, if both lab and POC may give bad results, which should I trust?

Unfortunately, the answer is not clear-cut. It is likely that pre-test issues (how the sample is collected and handled) play a substantial role in getting erroneous INR results.

With the POC INRs, you should use appropriate technique, store and care for the device and test strips properly, and be alert to changes in other medications that might alter the INR result. With lab-based INRs, you have to rely on the technique and attention to detail of a particular laboratory. Therefore, my own view is that clinicians should try to identify a laboratory that is reliable and use that lab as much as possible. Regardless of the method, if the INR result does not "fit" with what is expected, it is always reasonable to question the accuracy of the test and repeat the INR with a fresh blood sample.

Lastly, certain conditions can interfere with the INR test. The most widely known of these conditions is called antiphospholipid antibody syndrome. Lupus anticoagulant and anticardiolipin antibodies are 2 sub-classes of antiphospholipid antibody syndrome 

(www.clotcare.org/apsandlupusanticoagulant.aspx). Although people with these conditions are more likely to get blood clots, these conditions may cause the INR result to be falsely high. Such interference can lead the clinician to think that the patient is getting too much warfarin. In our own clinic, if we suspect this type of interference, we obtain a lab test called the chromogenic factor X (fX) level, which is a measure of warfarin effect that is not altered by the antiphospholipid antibodies. Unfortunately, fX levels are not available onsite in our clinic and may take a few days to get the result back.

And so, where do we go from here? It is not at all clear. INR tests are somewhat unreliable, and I guess all that we patients can do is bear this in mind, and if we have a test that appears to be unexpected, perhaps have a re-test to ensure that it is right.

How accurate are INR tests between different systems?

It has always seemed to me to be very hard to find out just how accurate INR tests from drawn blood taken at pathology labs are - for example, if they indicate your INR is, say 2.5, is it really between 2.3 and 2.7, or 2.45 and 2.55 - that is, in technical terms  what is the standard deviation of the test  or just how accurate are they.

Well I have found a study comparing INR as determined on the CoaguChek S (Roche Diagnostics, Indianapolis, IN), CoaguChek XS (Roche Diagnostics), and i-STAT 1 (i-STAT, East Windsor, NJ) point-of-care (POC) analyzers compared with venous plasma INRs determined by a reference laboratory method.

The abstract of the paper said

" Overall agreement between POC (Point Of Care) and laboratory plasma INR was very good, with median bias between capillary whole blood and laboratory plasma INRs varying from 0.0 to –0.2 INR units on all devices. More than 90% of results on the CoaguChek XS and i-STAT 1 and 88% of CoaguChek S results were within 0.4 INR units of the reference laboratory method. The CoaguChek XS and i-STAT 1 demonstrated greater accuracy than the CoaguChek S as measured by the number of results that differed by more than 0.5 INR units from the reference method. Median bias between CoaguChek S capillary whole blood and laboratory plasma INRs changed over time, demonstrating the need for ongoing quality assurance measures for POC INR programs."

Sounds heavy stuff.

But at least there is some indication that there can be differences between the various systems  sometimes up to 0.5 INR units or more. Further there is some indication that over a period of months, the relationship between the various systems changed.

But the problem is that I still have not been able to find out just how reliable or consistent the INR method relying on drawn blood by a pathology lab is. All this paper does is to compare various systems for measuring INR without indicating the reliability of each method in returning consistent results from a single sample. The article is well worth reading, and you can find it here

What are your options for INR / Warfarin tests when travelling?

Don't forget to check out our webpage at http://sites.google.com/site/inrtestingfortravellers/  for even more information! And please support our sponsors.

There are really only two options to get an INR when travelling - Do It Yourself, or use local Medical Service Providers

Do It Yourself

First a disclaimer - I have nothing to do in any way with the item I have described below, and I don't own one.

Recently, Roche Diagnostics have introduced an INR monitor for home use - the CoaguChek XS.. The monitor is about palm size, gives rapid results in under one minute, and requires only a small drop of blood (about 10 microlitres) for results. It seems ideal for travellers. But of course, there is always one drawback, and that is the cost. In Australia, the prices are between about $A770 and $A900 for the unit, and each test strip (one per INR test) is about $A6. The website for the Coaguchek XS is http://www.coagucheck.com/

Advanced Cardio Services offer the new CoaguCheck XS system, using exclusive smart technology to give you fast accurate results from a simple fingerstick test. as shown on their Home Page. There is also a video of how to use the unit, which seems very straightforward, together with a lot of other information about INR testing. Well worth a look. Advanced Cardio Services is based in California.

It seems to me, that if you are contemplating a reasonably long trip overseas, this may be the best and simplest option. I understand that they are generally available world wide. The use of such a monitor may prove more economical than using local doctors and pathology laboratories, and certainly will reduce the time wasted in organising doctor's appointments and blood tests.

I expect that there are probably other INR self testing kits produced by other manufacturers, and that if anyone is aware of these, I will also include them in this page - please use the Medical Services Feedback Form on the website above to provide me with any relevant information

Through Medical Services

Each country has its own procedures and methods - click here for Procedures and Costs for INR tests in particular countries.

INR and warfarin tests for travellers

Procedures for INR testing by country , and

Tips for finding doctors and pathology services when travelling

I have set this site up following a recent visit that I made to the USA, from Australia. I was in the USA and Canada for 6 weeks, and needed at least 2 tests for INR Warfarin during this time. In Canada, the procedure was reasonably straight forward, but it was a nightmare in the USA.First a bit of background - I had spent some time on the web prior to departure trying to figure out locations, procedures and costs in the US and Canada, but got little value from the information available.

Another problem turned out to be the different terminology between countries. In Australia, you go to a Pathology Laboratory for INR testing, but Pathology labs in the US and Canada are virtually all Speech Pathology related. Apparently in the US and Canada and other countries you need a Medical Laboratory or Clinical Laboratory or Diagnostic Laboratory for INR tests - and they proved hard to find easily. On this blog and the INR Warafrin website (see above), l have generally tried to use the term Pathology Laboratory to cover all types

I took with me to the US all of my medical records, my recent INR tests, and a referral from my Australian doctor. All of which proved useless. When I arrived in Canada, I was advised that I needed to get a local doctor's referral for an INR test - the cost for about 3 minutes with the doctor was $90 Canadian. The INR test was then done at a Clinical Laboratory only a short distance from the doctor's, and the cost of that was about $20 Canadian.

In the US I found it almost impossible to find a centre which could test me, and finally found one on the web, which turned out to be a local hospital. When I went in for an INR. they admitted me(!), wrist band and all(!), and after waiting in Emergency (!) reception for about 3 hours, they took my blood, and they did the test at that site. The bill for the hospital and doctors exceeded $US800, and the INR test was about $20 US!!! Total time with doctors about 5 minutes.

So this blog and the INR Warfarin website has been set up to assist overseas traveller's in the procedures and likely costs for INR testing

Finally, there is also additional information on our website at

http://sites.google.com/site/inrtestingfortravellers/

We need your help in developing this site!!

Currently there is information available about a few countries , and in the future I intend to expand the coverage considerably! But we need assistance from those travellers or locals who have had INR measurements taken in different countries!!

If you have any experiences in getting INR tests when travelling or in your local country, please either:

(i) make a post to this blog with full details of the country involved, the need for a doctor's referral for INR measurement, and costs of doctors and INR tests, and any other comments, or, perhaps better still -

(ii) fill in the Travellers Feedback Form on our INR Warfarin website, so that I can expand the information available to all who visit this blog and the INR Warfarin website.

Similarly, any feedback from medical providers, or equipment manufacturers of personal INR testers should reply either by adding a post to this blog, or by using the Medical Services Feedback Form on our website.I will then endeavour to make all relevant information available to visitors to this blog and the INR Warfarin website.

Finally, support our sponsors!

Many thanks!!!