BLOOD THINNING WITH WARFARIN (COUMADIN)

 

Warfarin is a compound of significant medical importance. Over the last 40 years, thousands have used it, and used it safely and effectively, to prevent strokes, heart attacks, clots in the legs (deep venous thrombosis), clots to the lungs (pulmonary emboli), and other disorders. It decreases the tendency of the blood to clot, and is very potent in doing so. It is a medication that must be taken with great care . . . it's not difficult, but it is important to "follow the rules" to maximize the benefits and minimize the potential adverse reactions.

This is a long article . . . it is not meant to scare you or confuse you. It is meant to explain the what's, how's, and why's of warfarin. You don't need to know everything about Warfarin, but please pay attention to these "Most Important Points" . . . we'll repeat them at the end again.

THE MOST IMPORTANT POINTS

 

What does warfarin do?  Warfarin is one of several types of medications which "thin" the blood. That is, they oppose the tendency of the blood to form clots.

There are two opposing "systems" in the blood -- one tends to make clots and is activated when there is a cut or other trauma, and the other slows down the tendency to clot, so that clots don't just keep on growing. Clotting occurs when certain substances (which are generally specific proteins made by the liver) interact in specific ways with other elements of the blood called platelets. Warfarin tips the balance a little bit, but not totally, in favor of decreasing clotting.

How does it work? The liver is the body's main factory. Here, sugars and fats and proteins are broken down and others are made. It is the site where the body makes the proteins it uses to cause the blood to clot. The body's action in blood clotting is quite complex, and uses a series of proteins secreted into the blood by the liver to interact with other substances found in the blood.

Warfarin slows the production of some of these clotting proteins that are made in the liver. It does so by inhibiting the action of Vitamin K which promotes the formation of some of the clotting proteins.

Who can be helped with warfarin? There are several conditions in which warfarin is used. Let me hasten to add that not everyone with these conditions will benefit from warfarin. The list below does not list all possible conditions for which warfarin is used.
  • Clots in the legs or other parts of the body ("Deep Venous Thrombosis") which have the potential to break loose and go to the lungs ("Pulmonary Emboli"). Pulmonary emboli can be very dangerous.
  • People with many types of artificial heart valves.
  • Some people who have a specific type of irregular heart beat known as "Atrial Fibrillation". In this condition, clots can form in the left atrium, and then become dislodged and travel to other parts of the body. If they become lodged in an artery to the brain, they can cause a stroke.
  • Some people who have had strokes or "Transient Ischemic Attacks" ("TIA's").
  • Some people who have had heart attacks.
  • Some people with blocked arteries.
  • After knee or hip surgery, generally for just a few weeks or months.
  • Some people with certain types of abnormal clotting disorders.
What else is it used for? Warfarin is still used as rat poison. That always gets your attention! I mention it not to scare you but to make an important point: If taken in large quantities, warfarin can cause severe and even fatal bleeding. When given as a medication however and monitored by blood tests, it can be quite safe.

When we put it out as rat poison, we use incredibly large quantities . . . and we don't check the rat's blood tests, either. So . . .

Don't be a rat . . . get your blood test checked as directed!

What's a "Pro time", and what's the "INR"? The "Pro Time" (or "prothrombin time" or "PT") is the name of the test which is used to monitor the effects of warfarin. It measures the tendency of your blood to clot as compared with a normal ("control") sample. It is expressed as the number of seconds it takes for the blood to clot, and may be expressed as a ratio of the blood sample to the control.

The "INR" (the "International Normalized Ratio") expresses the speed of blood clotting and corrects for any inconsistencies in the control samples. It is a more accurate expression of the action of warfarin and it is currently recommended that the "INR" be used as the number to adjust the dose of warfarin.

What should my INR be? It depends on the reason you're taking warfarin in the first place. For most conditions, the INR is optimally kept in the range of 2.0-3.0. For some conditions, the desireable range is higher, around 3.0-4.0. This is a goal that has to be set by your physician, depending on a number of factors about your condition.
These doses seem so "odd". Why? Individual people (and their livers) vary widely in terms of how much warfarin it takes to inhibit the action of Vitamin K on the clotting factors. Warfarin dosing can often be a bit odd.

First of all, there is really no way to tell for sure even what range a person's dose will be in. A little 80 pound lady may need 20 milligrams a day, and her 250 pound son may only need 2.5 milligrams a day. Again, this is why the blood test is necessary.

Second of all, the dose often needs to be quite specific to get to the goal INR. It is not uncommon to have people take 5 milligrams on one day, and alternate this with 2.5 milligrams on the next day, and so on. Or the dose may be "2.5 milligrams daily, except take 5 milligrams on Friday". These "odd" doses are necessary to keep the warfarin "balanced just right" for the particular person.

 

What do the pills look like? The pictures below are of Coumadin produced by DuPont.  Be careful. Notice how the pills look similar to one another. The colors are too similar to trust this as an accurate identification. Look carefully at the number on the pill to make sure it is correct.

Always double check your pills. If they don't match your old ones, don't take them -- talk to your pharmacist.

They are scored, so they may be cut in half if necessary.

What are the side effects? The major side effect of warfarin is simply bleeding. This is generally minimal as long at the PT/INR is kept in the therapeutic range. People on warfarin, even at desireable levels, may notice that they bruise more easily than usual.

Otherwise, warfarin is well tolerated. Side effects which sometimes occur include:

  • Hair loss
  • Nausea, vomiting, cramping or diarrhea (these are quite uncommon in my experience).
  • Low white blood cell counts.

These effects however are quite uncommon. As with other medications, other "rare" side effects have been reported. You should ask your physician if you have any concerns about whether these or different side effects may be occurring.

 

What are signs of bleeding and other things that should be checked out? The general rule is that bleeding which is occurring for "no good reason" needs to be checked out. The bleeding does not need to be severe, just unexplained. This may include:
  • Bleeding from cuts or from your nose which does not stop.
  • Throwing up blood, or material that looks like "old coffee grounds".
  • Finding blood in your bowel movements, or seeing very black and "tarry" stools. Tarry stools may indicate bleeding in the intestinal tract, which can turn this color and consistency as it passes through the GI tract.
  • A large bruise which keeps on growing . . . or a significant increase in the number of bruises you are experiencing.
  • More bleeding than usual when you brush your teeth. People on warfarin often have a little bleeding from the gums after brushing, but an increase in the amount may indicate that the dose is too high.
  • Blood in the urine.
  • Unexpected or more bleeding from the vagina. Menstrual flow may be considerably heavier.
  • Persistent headaches or dizziness
  • Weakness, being a lot more tired than usual. These may be signs of anemia from possible blood loss.
What if I get in a car wreck? You should be more inclined to go to the emergency room or doctor's office to get checked out. This goes for falling and hitting your head, or other traumas experienced in everyday life.

Heavy contact sports need to be avoided.

Are there any other medications I need to be careful about? Warfarin has a large number of interactions with other drugs. They occur for a variety of reasons:
  • Some medications thin the blood through other mechanisms, such as inhibiting the action of platelets. In this case, the clotting system gets a "double whammy", and this may lead to an increase in bleeding.
  • There can be changes in how drugs are "carried" in the blood.
  • Medications such as antibiotics interfere with the action of bacteria in the gut, who have a lot to do with the availability of vitamin K.
  • Effects on liver metabolism can be important as well.

The list of possible interactions is long, and there are medications which increase and some which decrease the effects of warfarin. The most important medications are:

  • Aspirin, which is also a blood thinner. Aspirin works by inhibiting the clotting functions of platelets, the formed elements of the blood involved with clotting. Aspirin is sometimes given on purpose with warfarin in certain conditions. However, unless it has been specifically prescribed for you, aspirin should be avoided while you are on warfarin. Persantine, Ticlid, and Plavix are similar drugs.
  • Acetaminophen (Tylenol and other "non-aspirin containing analgesics") may interfere with the metabolism of warfarin. Recommendations vary, but I ask people to give me a call if they are taking more than about 6 tablets of these agents a week.
  • Antibiotics (some, not all) may interfere by reacting with the way warfarin is carried in the blood, by interfering with the metabolism in the liver, or by changing the metabolism of Vitamin K.
  • Non-steroidal anti-inflammatory agents, which are widely prescribed, and available over-the-counter, for aches and pains of arthritis.

I'll stop the list here . . . it could go on . . . at length.

What is most important is

  • Tell anyone who is prescribing you medications whether they are aware that you are on warfarin, and whether there are any effects on its metabolism.
  • Double check with your pharmacist.
  • Don't take over-the-counter medicines without checking it out.
Why do I have to pay attention to my diet? As if the rest of this wasn't enough, your diet is actually quite important. This is because the synthesis of the clotting factors in the liver depends on the availability of Vitamin K. Therefore, the amount of Vitamin K in the diet can change the effects of warfarin.

This needs not be too complex. The most important point to remember is to keep the amount of Vitamin K fairly constant. Wide swings in intake may cause the PT/INR to change a significant amount. Be aware of foods that are particularly high in Vitamin K, and try to keep the amounts fairly constant.

There is a "Coumadin Cookbook" which has been recently published. It gives the Vitamin K contents of hundreds of recipes. A link detailing more about this can be found at:

   http//:www.coumadincookbook.com

 

What foods are high in Vitamin K?
  • Kale, spinach, and many green leafy vegetables.
  • Broccoli, cauliflower, and brussel sprouts.
  • Green tea
What foods are low in Vitamin K?
  • Meats, poultry, and shellfish
  • Many vegetables such as squash, radishes, turnips (without the greens!), potatoes, eggplant, mushrooms, onions (not spring onions).
  • Breads, crackers, bagels, etc.
  • Rice and pastas
  • Most fruits (the skins may contain a fair amount of Vitamin K) and their juices
  • Dairy products
  • Coffee, tea (but not green tea), and colas

See, you're in great shape!

Is there a particular time of day I should take warfarin? Although it is not a critical issue, most physicians strongly encourage you to take warfarin in the evening. This is only because Protime blood tests are typically done in the morning and reported to the physician's office a little later. You find out your dose after this.

To be able to change the dose if needed as soon as possible it is best to take warfarin in the evening.

 

What if I want to become pregnant? You must stop warfarin while you are pregnant. It is associated with significant birth defects. Let your physician know immediately.

You may be a candidate for Heparin therapy (see below).

What else do I have to be careful about? You should take care not to overindulge in alcohol. This can affect the way the liver metabolizes, and we've already talked about the importance of this. Different physicians handle this matter differently as well. My advice to my patients is to drink no more than two drinks per evening. "Binge" drinking is particularly to be avoided -- it can "shock" the liver, and interfere significantly with the protime.
This sounds dangerous . . . isn't there anything else I can take? Well, there are alternatives, and your physician has most likely considered them. For now, warfarin has an important place in the treatment of certain medical conditions, and trials to this point have not found suitable alternatives in many situations.

Although aspirin is a blood thinner, it may not be potent enough for many circumstances. Other agents like dipyridamole (Persantine), ticlodipine (Ticlid) and others do not do enough in many cases (although they may be preferred over warfarin in other cases).

"Heparin" is an agent that has been around for years. It is frequently given continuously intravenously for some conditions, but this is not practical for long term therapy. However, it has been given subcutaneously once or twice daily for long term therapy in some situations. This can be associated with osteoporosis, low platelet counts, and a few other side effects. Newer formulations minimize these side effects. It is administered with a needle under the skin. It is not used widely at the current time, but may be a good alternative in some people in some circumstances..

An umbrella-like device (a "Greenfield filter") can be placed in a vein (the inferior vena cava) to block the passage of clots from the legs to the lungs. After this is placed, the person may no longer need to take warfarin. These are not a cure-all either, and the filters have their own side effects and risks.

 

What if I miss a dose? Different physicians and clinics handle this differently. My rule of thumb is: If you remember within 12 hours of the missed dose, go ahead and take it then. Otherwise, omit that dose. Do make a note of it, and tell the person who gives you warfarin instructions next time you talk to them.

 

How long do I need to take warfarin? For some conditions, it may be only weeks or months. In many cases however, it is a lifelong medication.
How often do I need to get my blood test? When just getting started, the protime is measured every 3-7 days for a while. It is sometimes even checked daily in some circumstances.

As the dose stabilizes, the interval gradually increases to as long as once per month.

Don't ever go longer than you have been told between tests, even if your dose is very stable.

 

Isn't there an easier way to get my blood tested? There is a home test available. It is not exceedingly simple, but it is not all that difficult either. It certainly can be a convenience. You need to discuss this with your physician to set it up. Not all insurance companies cover the cost of this device.

You can check this out further at:

http://www.itcmed.com/protime/

What if I need to go to the dentist, or have a medical procedure? You will need to let the professional who is doing the procedure know that you are on warfarin at the time you schedule the appointment or procedure. Warfarin generally needs to be stopped for 3 days prior to a dental or surgical procedure. The specifics of management depend on your particular case and the procedure performed.
How do I keep a calendar? Just get any old calendar, and carry it in your wallet or purse, or hang it on the refrigerator. When you talk to the person who gives you warfarin instructions, then:
  • Write down the PT and INR results in the square on the day it was performed.
  • Write "Blood Test" (or something appropriate) in the square for the day you are instructed to get your next Protime.
  • Fill in the dose you are to take in each of the squares until the next blood test.
  • Circle each day's dose as you take the pill, so you can remember you took it.
Are there any other links? How about the Coumadin package insert online?

http://www.coumadin.com/coumadin/cumadnpi.htm

The link to Barr Laboratories, another manufacturer of warfarin:

http://www.barrlabs.com/


THE MOST IMPORTANT POINTS (I told you we would repeat them)

 




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