INRs that Fluctuate – Solutions

Background and summary

The cause  of fluctuating INRs in patients on warfarin is often not clear.  The following causes should be considered. Solutions how to deal with fluctuating INRs are listed further below.

Causes

1. Diet: Is the diet inconsistent or have there been dietary changes that would change the patient’s vitamin K intake?  It does not matter whether the patient eats a lot of vitamin K containing foods or a little – the consistency counts.
2. New prescription medication: Has any prescription medication been newly started or discontinued?
3. Over-the-counter medications: Is the patient taking any new types of over-the-counter medications, vitamins, herbs, homoeopathic medications, and weight control or energy booster pills?
4. PRN medications: Is the patient taking additional medications  – e.g. pain medications – on an as-needed (PRN) basis, on some days taking higher and on others lower doses.
5. Time of medication intake:  Is the patient taking his/her various medications at similar times every day?
6. Interfering medications:  Are any other medications taken close to the time when the warfarin is taken?  Some drugs interfere with the absorption of warfarin and should, therefore, not be taken at the same time, but rather a few hours earlier or later than warfarin.
7. Correct medication intake and compliance:  Is the patient taking his/her medication religiously or does he/she miss doses or take double the dose at times?  Since various warfarin tablet sizes exist, and some patients have different tablet strengths at home, has the patient confused the different tablet sizes?
8. Vitamin supplements: Is the patient taking a multiple vitamin tablet or other supplements that contain vitamin K and only takes these vitamins or supplements irregularly? It is o.k. to take these but they need to be taken consistently.
9. Stress, physical activity:  Has there been an unusual amount of stress, sleep deprivation, or physical activity in the days preceding the INR test?  While I am not aware of any published data on this issue, it is possible that in some patients there may be an influence on the INR (increase or decrease), possibly through changed metabolism of warfarin.
10. Inflammatory disorder, diarrhea, and congestive heart failure:  Does that patient have an inflammatory disorder, recurrent diarrhea, or congestive heart failure that fluctuate in activity over time?
11. Lupus anticoagulant: Does the patient have a lupus anticoagulant?  In some patients the lupus anticoagulant can have an influence on the INR.  Since lupus anticoagulant levels can fluctuate over time, the INR can fluctuate as well. Furthermore, if the lab changes its reagents or the INR is tested in different labs, discrepant INR results are possible in some patients with lupus anticoagulants.  Similarly, discrepant values may be seen if finger-stick point-of-care method and at other times a phlebotomy method is used to draw blood and determine the INR.
12. Lab error: Was the out-of-line INR a lab error?
13. Shelf life: Was the warfarin taken outdated?  Efficacy of the drug is only guaranteed for the time printed on the package.

Solutions

1. Take similar warfarin dose every day: INRs may become more stable if the patient takes a similar dose of warfarin every day, rather than different doses on various days of the week (see figure vitamin K supplementation).  The weekly dose a patient is taking should be calculated and divided by seven – and tablets close to that daily dose taken (figure). Since warfarin tablets come in a number of different doses, such more consistent dosing is easily possible.
2. Switch to brand Coumadin® or Jantoven®: While generic and brand warfarins have been shown to be bioequivalent [ref 1], switch from generic warfarin to brand Jantoven® or Coumadin®. This sometimes helps stabilize the INR.
3. Take daily vitamin K supplementation:  A daily vitamin K tablet, such as 100 or 150 mcg per day can stabilize the INR in some patients [ref 2].  Such vitamin K tablets can be bought in health supply stores without prescription. When starting daily vitamin K supplementation, a patient may need higher warfarin doses to keep the INR in the therapeutic range. Therefore, the INR should be checked within a few days (ca. 3-4 days) once vitamin K has been started, and should be monitored closely in the weeks thereafter.
4. INR home monitoring:  INR monitors are available for INR home testing by patients and are often reimbursable by insurance companies. Reimbursement allows weekly testing. This may lead to more stable INRs in some patients.
5. Switch to Xarelto®: One could consider switching the patient from warfarin to one of the injectable anticoagulants or to the new oral anticoagulant Xarelto® (rivaroxaban).

References

1. Kesselheim AS et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA 2008 Dec 3;300(21):2514-26.
2. Ford S, Molls. Vitamin K Supplementation to Decrease INR Variability in Patients on Vitamin K Antagonists: A Literature Review. Curr Opin Hematol. 2008 Sep;15(5):504-508
3. Schulman S et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-5.

For patients

This same post, written for patients, can be found at https://clotconnect.wordpress.com/2010/11/20/inrs-that-fluctuate/

Disclosure:  I have received support for a research study investigating the performance of point of care INR monitors in patients with antiphospholipid antibodies from Roche Diagnostics, International Technidyne Corporation (ITC), and Hemosense. I have consulted for ITC and Janssen.

Last updated: March 29th, 2013