Warfarin Institute of America

DEDICATED TO YOUR HEALTH SINCE 2000

THE USE OF VITAMIN K

  The first part of this page is about treating a high INR.  If you are looking for advice about multivitamins, go to the last section. 

If you are looking for information about food click here.

  Vitamin K is an antidote for warfarin.  This applies whether you are treating a high INR, looking for a multivitamin to take, stopping a multivitamin, or thinking about changing what you eat.

This Section Reworked and Updated by

Melissa Rodgers, Pharm. D. Candidate

University of Colorado Health Sciences Center

School of Pharmacy 

Vitamin K and High INR

Vitamin K 

  Vitamin K (phytonadione, Koagulation Vitamin) is necessary for the liver to make the some of the components the body uses to form a clot (coagulation Factors II (prothrombin), VII, IX and X).  It is found in food items, such as green leafy vegetables, and some vitamin formulations.  Vitamin K is the antidote for warfarin.  Because Vitamin K reverses the action of warfarin, it is used in some patients whose INR has risen too high.  Vitamin K brings the INR back down.¹ 

High INR

(Synonymous terms:  supratherapeutic INR, excessive anticoagulation, warfarin toxicity)

  The INR range is determined based on the disease being treated and the associated risk of clotting.  For most diseases, the desired INR range is 2-3, though there are some desired ranges of up to 3-4.5.  The INR range represents the best balance for most patients to have a decreased risk of experiencing a clot, without greatly increasing the risk of experiencing a life-threatening bleed.  When the INR is too high, such as 4-9, the risk of experiencing a bleed is increased.  The treatment options are based on how high the INR has climbed and the presence of active bleeding.²   

Risk of Major Bleeding With a High INR 

  The risk of patients having major bleeding during a high INR of 5-9 is relatively low.³ A study performed in a group of warfarin-treated patients evaluated the patients who experienced an INR of greater than or equal to 5.  The patients were followed for the 30 days after their INR was found to be too high to determine how they were treated and if they had a major bleeding episode.  Out of 979 patients included in the pertinent results data, 13 experienced a major bleed in the first 30 days of a high INR (1.3%).  Most of these occurred in the first week, and were associated with the gastrointestinal tract.  None of the bleeds caused death.³ Out of 934 patients whose INR’s were less than 9, 34 patients experienced minor bleeding,³ such as nose bleeds. Most of the patients were treated by omitting upcoming warfarin doses and monitoring more frequently until their INR decreased.  The patients with major bleeding were also treated with Vitamin K.³ 

References: 

1.  Klasko RK (ed).  Phytonadione DRUGDEX® System.  Thompson Micromedex, Greenwood Village, Colorado (Edition expires [3/2006].

2.  E.N. Libby and D.A. Garcia, A survey of oral vitamin K use by anticoagulation clinics, Arch Intern Med 162 (2002), pp. 1893–1896. 

3.  D.A. Garcia, S. Regan, M. Crowther, E.M. Hylek, The Risk of Hemorrhage Among Patients With Warfarin-Associated Coagulopathy.  Journal of the American College of Cardiology 2006; 47:804-8.

©2006 Melissa Rodgers - Used by Permission

Using Vitamin K to Smooth-Out Fluctuating INRs

If you walk into a dark room and switch on a 3-way light you notice a huge increase in the amount of light.  If you switch to the next higher level, you do not notice as much change even though the increase is the same number of watts.   

It appears that a similar thing happens when someone takes in very little vitamin K from eating vegetables.  If this person then gets a little more vitamin K than usual, the INR can be thrown off.  To get around this, some warfarin managers have tested giving people a known amount of vitamin K.  Then they managed whether or not the INRs became more consistent.   

A study done in the UK followed 70 people who had unstable INRs.  They were divided into two groups – those getting 150 mcg of vitamin K daily and those getting a placebo.  The people getting the vitamin K had more consistent INRs than the people getting the placebo.  Each person’s INRs for 6 months on the study were compared with their INRs for 6 months before the study. 

It appears that taking a known amount of vitamin K daily and adjusting the warfarin dose upward to accommodate this, results in more stable INRs.   

Reference: Sconce E. et al. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin.  Blood. 2006; Nov 16. (E Pub Ahead of Print).

To Reverse an Elevated INR 

The Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy Recommendations for Managing Elevated INRs or Bleeding in Patients Receiving Vitamin K Antagonists. 

Ed. Note: I can only measure INRs up to 8.0.  If a person is not bleeding, I am reluctant to give vitamin K because it may not do any good and may cause clotting.  I have the patient hold warfarin until they can be rechecked – usually 48 to 96 hours later.  I instruct them that if bleeding starts, they are to go to the ER and tell them that they have an elevated INR that was being treated by holding warfarin but now they have started bleeding.  This always puts them near the top in urgency.  After about 25,000 patient visits this method has never resulted in serious harm to a patient.

FOR A DISCUSSION OF THE CHOICE BETWEEN VITAMIN K AND FRESH FROZEN PLASMA CLICK HERE

  Wu et al report on a study of reversing warfarin for patients with INRs between 3 and 20 conducted at a teaching hospital affiliated with a world-renowned medical school.  Fresh frozen plasma (FFP) was used in 22 patients.  According to the guidelines published with the article, this was the correct agent to use in 21 of those patients.  However, only 5 of the patients received the correct dose of FFP.  There were an 21 patients who should have been given vitamin K according to the guidelines.  Of these, only 14 were given vitamin K.  Of those 14, none received the correct dose. Editor's Note:  Not only is vitamin K being misused, the doctors in training are being taught to misuse it. 

  Wjasow and McNamara report on the death of a 78-year -old woman who had an INR that was too high to calculate, but had no signs or symptoms of bleeding.  The American College of Chest Physicians in effect at the time of the incident recommended giving vitamin K 10 mg intravenously by slow push.  The woman was given only 1 mg (1/10th of the recommended dose) and she died within two minutes.  This was in spite of her being given the dose in an emergency department and all available drugs and resuscitation equipment were on hand and instantly utilized.  Fortunately the guidelines have been modified since this time and now take a much more conservative "wait and see" approach if the person is not bleeding.  (The very day that I received this report I was contacted by a physician who wanted to give a person a 10 mg injection of vitamin K to reverse an INR that was in the correct range, but the an elective procedure was going to be done.)

  The Journal American Family Physician published a case study where the author conceded that there was an overly aggressive response to a bloody nose.  The patient was a man with mechanical heart valve who had a bloody nose of two hours duration.  His INR was found to be 4.7,  The bleeding was controlled by packing the nose and including bacitracin, oxymetazolone and cocaine.  (Not that the bleeding was controlled at this point.) Then they injected him with vitamin K 2.5 mg subcutaneously, administered 2 units of fresh frozen plasma and held his warfarin for 5 days.  Ten days later his INR was only 1.7.  He was put at high risk for a thrombus by using vitamin K, fresh frozen plasma and holding warfarin all after the bleeding was controlled.  Holding the warfarin for one day should have been sufficient in this case after the bleeding was controlled.

  When there is no bleeding, just an elevated INR, I use the approach advocated by Witt et al.  They state that at INRs of 4.5 to 10.0, the risk of major bleeding is not high enough to warrant rapid INR reversal with vitamin K.  I do not have prescribing authority, so I must request that a physician order vitamin K therapy.  I seldom request this if a patient is not bleeding.  The only exceptions I can think of are when patients live many miles from health care.  Then I have asked for a prescription to be used only if the patient begins to experience bleeding.  For patients who are healthy enough to come into an outpatient clinic and live near the hospital, the chances of a life-threatening bleed are very small.  As Witt et al state, "We believe that the INR overcorrection frequently seen after vitamin K administration is worrisome in non-bleeding patients with INRs between 4.5 and 10.0, especially when the underlying thromboembolic risk is high."

  Patel et al conducted a randomized, double-blind, placebo-controlled study of using vitamin K 2.5 mg orally.  They studied patients who had INRs between 6 an 10 and gave them either a single dose of vitamin K 2.5 mg or a placebo.  Warfarin was stopped until the INR fell back to below 4.0.  The people who took the vitamin K had their INRs come down faster, but they also came down farther and dropped too low more often than the others.    Neither group had significant warfarin resistance when they restarted  warfarin.

  How long should you hold warfarin?  I think that it depends upon the dose of warfarin.  The average dose of warfarin seems to be about 4 or 5 mg per day.  This is the average dose because these people are about average in their metabolism of warfarin.  With this dose, the INR should decline to about half of its previous level in about 48 hours.  So if someone taking 3 to 6 mg of warfarin per day has an INR of less than 8, their INR should be back below 4 in two days.  (A statistical analysis of about 2,500 visits to my clinic found no additional risk of bleeding with an INR less than 5.0.) Therefore, I feel confident in having these people rechecked in two days.  When someone who takes less than 3 mg of warfarin daily (a slow metabolizer),  they will usually not have their INR decrease by half in 48 hours.  I will check this person again in 48 hours to be sure that they have not developed bleeding.  However, if they had a INR of near 8, their INR will usually still be above 4 after 48 hours.  They often need to be checked again in another 48 hours.  When someone takes more than 6 mg of warfarin daily (a rapid metabolizer), I am reluctant to hold warfarin for more than one day.  They will usually have their reduced by more than half in 48 hours.  

  How much vitamin K do you give when it is needed?  I have seen an INR of 9 reduced to less than 2 within 24 hours of giving 2 mg of vitamin K IV.  I have also seen a patient with moderate bloody diarrhea and an INR of 7.4 have the diarrhea resolve within 24 hours after an oral dose of 11.25 mg of vitamin K.  (He had used all of his sick days and declined to come back to the clinic after the diarrhea resolved, so I do not know what the after-treatment INR was.)  I probably would not use this large dose today, but it was advocated a few years ago.  I think now that 2.5 to 5 mg of oral vitamin K would have been sufficient.

References: 

Ansell J et al. The pharmacology and management of the vitamin K antagonists. Chest 2004; 126:204S-233S.

Beanland DR. Monitoring Warfarin Therapy (letter). Am Fam Phys 1999;60:764.

Witt DM et al. Vitamin K for warfarin-associated coagulopathy.  Lancet 2001;357:718.

Patel RJ et al. Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation

Wjasow C, McNamara R. Anaphylaxis after a low dose of intravenous vitamin K.  J Emerg Med 2003;24:169-172.

Wu BJ et al. Reversing warfarin anticoagulation: Utilization of fresh frozen plasma and vitamin K in a community hospital. J Clin Outcomes Man 2003;10:643-5.

If you are looking for a general purpose multivitamin

  Look for a formula that does not contain vitamin K.  Two of the most readily available are One-A-Day for Women and One-A-Day for Men.  It does not have to be the exact brand.  Many stores also carry a generic or house brand with the same formula.  If in doubt, ask the pharmacist.

  A reader sent me an e-mail and said that Shaklee Formula I contains no vitamin K.

  If any other readers want to send me other brands that contain no vitamin K, please do so.  I'm not trying to endorse any brand.  

Hidden sources of vitamin K

  Ensure, Boost, Resource, Carnation Instant Breakfast, Luna Nutrition Bars for Women and many similar products contain vitamin K.  If you start, stop, or don't drink the same amount every day, you cannot expect to have your INR be anywhere near consistent.  I saw one young woman in her twenties who was eating three Luna bars per day.  These each contain 100% of the recommended daily allowance of vitamin K.  She had an Antithrombin III deficiency and this caused a stroke.  If you have been hospitalized, you may have been taking something along this line.  If you go home and do not continue the same amount of the same product, this will probably cause your INR to be off.

  If you have been on Total Parenteral Nutrition (TPN), sometimes called hyperalimentation you were probably getting vitamin K in the formula.  When you go off this, it is likely that your vitamin K intake will decrease, causing your INR to increase.  Also, some TPN formulas give vitamin K daily and some add it only one day per week.  The one day per week formulas are particularly bad for trying to control warfarin.  

  This one is really sneaky -- Meals on Wheels.  Who would think that a nice program like this would interfere with your medication.  However, think about who gets into this program.  Those who are not eating.  What is the first thing that the typical American gives up when they are unable to spend time preparing meals?  If you said vegetables, you are right.  What does Meals on Wheels provide?  A balanced diet with lots of vegetables.  Don't get me wrong, I'm not anti Meals on Wheels, in fact I have made referrals to them.  But, when people start this program they often need their warfarin dose increased.  So they should have the INR checked about a week after starting Meals on Wheels. 

  Stopping a vitamin which contains vitamin K

  If you are taking a vitamin that contains vitamin K, you cannot simply stop it.  One of the biggest problems I see in my clinic is people who either decide the vitamin is not helping with whatever they decided to take it for, or else they run out and have no money to purchase more until the next payday.  THIS CAN PUT YOU IN THE HOSPITAL WITH A BLEEDING EPISODE.  If you must stop a vitamin which contains vitamin K then, you must have your INR checked in the next 3 to 7 days.  Failure to do so can be disastrous.  

Answers to Thomas, a 9th Grader Working on a Science Project

  How much vitamin K is too much?  There is no set answer.  It depends on if you are talking about the amount to eat daily or the amount to treat an overdose of warfarin causing bleeding.  About 25 mcg is sufficient for a daily intake.  Doses over 10 mg to treat bleeding should be tailored to each individual.

  How closely would someone taking warfarin have to monitor their dietary intake of vitamin K?  I don't like for people to do this.  I tell people to eat what they like and we will adjust the dose of vitamin K around it.  I tell them to not go goofy and eat a whole bag of cole slaw mix in two days -- I have seen it done.  It throws the INR off for a few days but not too badly. 

  Would they be able to eat the recommended daily allowance of vitamin K?  Easily -- unless they were meatatarians (the opposite of a vegetarian).

  Is there a chemical reaction between vitamin K and warfarin?  Not in the usual way that you think about these things.  Vitamin K helps make several clotting factors in the body.  Warfarin prevents this from happening as efficiently as normal.  There is chemistry involved but not the kind of reaction that bubbles and smokes.

  Does vitamin K counteract warfarin  by having the blood clot easier.  Yes, but this a backward way of thinking about it.  Warfarin slows down the natural clotting ability.

  Is there a good balance between the amount of vitamin K intake and warfarin?  Yes.  It is different for every person.  The more vitamin K you take in, the higher the warfarin dose will be to keep the clotting level down to the desired level. 

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Last updated April 5, 2007