Medicine For People!
Safe Use of Warfarin AKA Coumadin
Table of Contents
- Coagulation: Good and Bad
- Blood Clots in the Legs
- Heart Attack
- The Discovery of Warfarin
- Do Not Try This at Home
- Adjusting the Dose
- Warfarin and Vitamin K
- The Research
- My Advice
This Month: Free Hard Copy of Your Original Medical Records
Safe Use of Warfarin AKA Coumadin
Imagine if you will a plumbing system that always works and never leaks. The water always flows easily, and should a leak appear in the pipes, the water enters the gap in the wall of the pipe, becomes solid, and stops the leaking.
You own such a plumbing system. Among the wonders of your blood is its ability to remain a liquid when in the blood vessels, yet to turn into a solid and plug any leaks when circumstances require.
The ability for blood to become solid is called coagulation. You see it at work whenever you cut yourself and a scab forms to stop the bleeding. Your coagulation system includes proteins and other clotting factors. It also contains platelets. Much tinier than red and white blood cells, these float along in the bloodstream and are shaped like-you guessed it-little plates.
As long as coagulation proteins remain inside the blood vessel, they stay liquid and all goes well. Think of them as the liquid silk in the spinneret of a spider. Just as the liquid in the spider's spinneret becomes a solid fiber upon exposure to air, under certain conditions coagulation proteins in the blood coalesce with each other, forming long fibrils very similar to a spider's web.
The last part of this system is the blood vessel lining, the endothelium; think of this as biological Teflon. As long as the blood is flowing along normal endothelium, it's not going to clot.
Coagulation: Good and Bad
Blood clotting prevents us from bleeding to death from the inevitable cuts and lacerations of ordinary life. The least little slice through the endothelium exposes the blood to a world as foreign to the blood as the surface of the moon. Exposed to any tissue except endothelium, the coagulation proteins and platelets are triggered into forming a solid clot and stopping the bleeding.
Unfortunately, this system can be triggered in other situations, leading to trouble.
Blood clots in the legs
Varicose veins can become inflamed. Not only is this painful for the individual, but the inflammatory chemicals in the lining of the vein can spoil the Teflon effect of the endothelium and trigger formation of a clot inside the vein. We call this thrombosis. In the worst case, these blood clots can travel to the lungs and cause death from what we call pulmonary embolism.
Most people in the Western world start to develop arterial plaque in their 20s, which increases in size throughout their lives. Plaque is a buildup of fats, calcium, and scar tissue. The plaque develops beneath the endothelium, which separates it from the blood, so all usually goes well. Let that plaque become inflamed, however, and it can erode a tiny hole in the endothelium. That tiniest gap in the Teflon can trigger the coagulation system to start up a clot right there in the middle of that coronary artery. If you will excuse the technical term, this is Not Good.
Other circumstances that can set off the clotting system are:
- foreign materials within the blood vessels system, such as an artificial valve or cardiac stent
- atrial fibrillation, a condition in which the atria, the priming chambers of the heart, do not pump normally, but just shimmy or fibrillate. Blood can pool in the left atrium and form blood clots, which then can become loose and travel to the brain, causing a stroke.
- antiphospholipid syndrome, a condition affecting women in which the blood is more likely to coagulate and lead to miscarriage, deep vein thrombosis of the legs, and stroke.
In all these cases, the sufferer usually benefits from anticoagulation. Many times the best choice is warfarin.
Warfarin and Vitamin K
The story of warfarin begins in the 1920s, when a Canadian veterinarian figured out that an outbreak of fatal bleeding in cows originated with the cows' ingestion of moldy clover. After a couple of decades of chemical sleuthing, the active substance was isolated, modified, and then employed as a rat poison in 1948 with the name warfarin. Rats would eat it and then bleed to death. You may know warfarin by its brand name, Coumadin.
Within a few years, human physicians began prescribing it as an anticoagulant.
Some of the coagulation proteins and clotting factors require vitamin K for their synthesis and activation. We get vitamin K from our food, especially leafy greens. A healthy intestinal bacterial flora adds to our vitamin K intake. Infants are routinely given an injection of vitamin K after birth to prevent bleeding. Many people with osteoporosis take vitamin K to enhance growth of healthy bone.
Warfarin interferes with vitamin K's support of the coagulation system.
Do Not Try This at Home
I believe that the following story, however strange, is true. A human of the species Geezer americanus needed warfarin for some good medical reason. He did not like going to doctors, and he was not wild about getting blood tests every few weeks to make sure he was getting the right dose, so he bought some warfarin rat poison and ate a pinch every day.
At some point he encountered a physician and told a physician his story. The doc asked "how do you know how much to take?" The man replied that if minor cuts from shaving or ordinary living bled too long, he would reduce the dose.
This kind of DIY medicine may sound appealing, but there's a good reason for having a doctor monitor your use of warfarin.
Adjusting the Dose
The major downside of warfarin is that if the dose is too low, the person may suffer a clot, with resultant pulmonary embolus, stroke, or heart attack. If the dose is too high, then they can bleed. Really bleed.
Although you may be able to tell when your dose is too high, you can't tell when it is too low-until something bad happens! So every few weeks, people on warfarin get a blood test to assess their degree of anticoagulation. These tests used to be called prothrombin time, or pro time, and are now called INR tests.
When the INR levels are within range time after time, we can check just once a month or so. When INR levels vary up and down, we may need to check every week. A change of warfarin dose usually requires several days to take effect, so it is easy to over-correct.
And this leads us to the urban myth this newsletter aims to correct.
Vitamin K and Warfarin
When you look up drug interactions with warfarin, you find warnings against using vitamin K, such as this one from the University of Maryland Medical Center.
"Vitamin K reduces the effects of the blood-thinning medication warfarin, rendering the medication ineffective. Vitamin K should not be taken while taking warfarin, and foods containing high amounts of vitamin K should be avoided."
In fairness to the University of Maryland, I suspect they have not looked at this particular page in some time. If you are reading this newsletter in our newsletter archives, do not be surprised if they have updated the information. But as I write in 2017, this is pretty standard patient instruction.
And that is the reason for this newsletter!
This standard advice ignores the importance of balance between vitamin K and warfarin. Yes, vitamin K interferes with warfarin to the point that we use vitamin K as an antidote to warfarin when needed. But no, you do not need avoid foods containing high amounts of vitamin K as long as you eat them regularly.
The environment inside the blood vessel, which contains normal amounts of vitamin K, and the coagulation proteins, the warfarin that the doctor has prescribed, and the Teflon lining, plus all the challenges of daily existence are in balance. The INR tells us what that balance is, a range that inhibits blood clotting but not too much.
Take the case of a conscientious patient who avoids green vegetables entirely. If we put the vitamin K levels in his bloodstream on a scale of 1 to 10, his would be a 1. Because of these low levels, he requires only 3 mg a day of warfarin. His coagulation system is in the desired balance. One day he has a salad, and the next day minestrone soup with some kale floating innocuously around. His vitamin K levels triple, now being 3 on the 10 scale. He gets his INR done and it's low, so his caregivers decrease his dose of warfarin. Now he is back to his normal routine, avoiding green vegetables, and his vitamin K levels fall, and the new dose of warfarin overpowers his coagulation proteins, and his next INR comes back high. Many patients and doctors wind up in this frustrating circle.
But nowadays, people involved in managing anticoagulation are revising this advice to avoid all food sources of vitamin K.
Imagine instead that our conscientious patient eats a normal diet, some green vegetables every day, and so runs vitamin K levels at, say, 5 out of 10. Because of these higher levels, he requires more warfarin, say 5 mg a day. His INRs run in the desirable range.
If he should eat an extra salad and serving of minestrone with kale, his vitamin K level will not triple, but will increase only by 10%. That is not enough of a difference to throw his system out of balance.
Several coagulation centers have investigated this phenomenon. For example, researchers at the Royal Victoria Infirmary assigned 70 people with unstable coagulation to take either placebo or vitamin K tablets. Six months later, 19 out of 35 on vitamin K tablets achieved stable control whereas only seven out of 35 placebo users achieved stable control.
Vitamin K intake varies from person to person, and of course there is a certain contribution from our intestinal bacteria. Most of us get about 100 µg of vitamin K in our daily diet. The vitamin K patients in the study just above took 150 µg extra daily. A thousand micrograms, abbreviated 1000 µg, is the equivalent of 1 mg.
This is not a great deal of vitamin K for a normal human. The dose we use as an antidote to warfarin overdose starts at 2.5 mg and runs up to 10 mg, with repeat doses for serious and dangerous bleeding.
If you decide to make a change in your nutrition and you take warfarin, be sure to discuss it first with the person who manages your anticoagulation. If you take any vitamins, look at how much vitamin K is in the vitamin. Do not change to a different multiple vitamin without reading the label and, if there's a change, talking to the person who manages your warfarin dose.
What I tell my patients is to eat a normal healthy diet, including green vegetables. Here a list of such vegetables and their vitamin K. We then adjust their warfarin dose to provide the appropriate degree of anticoagulation.
Notice that cooked kale, spinach, and collards contain especially high levels of vitamin K, about 0.5 mg (listed as 500 µg in the Wikipedia table). If you enjoy these, you will need to maintain a relatively constant intake through the week.
This Month: Free Hard Copy of Your Original Medical Records
Thank you for the positive response to our notice last month regarding disposal of our old paper copies of medical records. This is an ongoing process and we have now scanned most of your records into our computer system. For space reasons, we need to dispose of the old scanned records.
If you would like a copy of your medical records please send an e-mail request to firstname.lastname@example.org. If we still have your hard copies we will set them aside for you to pick up and notify you when they are ready. If they have already been shredded, we can give you an electronic copy on a USB drive.
Medicine for People! is published by Douwe Rienstra, MD at Port Townsend, Washington.