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WHAT IS WARFARIN? — Warfarin (brand name: Jantoven) is a prescription medication that interferes with normal blood clotting (coagulation). It is also called an anticoagulant. Warfarin is sold under the brand name Coumadin in some countries; however, this brand is no longer available in the United States or Canada. Many people refer to these medicines as "blood thinners," although they do not actually cause the blood to become less thick, only less likely to clot.
The normal clotting mechanism is a complex process that involves multiple substances (clotting factors). These factors are produced by the liver and act in sequence to form a blood clot. In order for the liver to produce some of the clotting factors, adequate amounts of vitamin K must be available. Warfarin blocks one of the enzymes that uses vitamin K to make some of the clotting factors, and in turn reduces their ability to work correctly in the blood. As a result, the clotting mechanism is disrupted and it takes longer for the blood to clot.
WHY DO I NEED WARFARIN? — Warfarin is prescribed for people who are at increased risk for developing harmful blood clots. This includes people with a mechanical heart valve, an irregular heart rhythm called atrial fibrillation, certain clotting disorders, or a higher risk of a clot after hip or knee surgery. (See "Patient education: Atrial fibrillation (Beyond the Basics)" and "Patient education: Antiphospholipid syndrome (Beyond the Basics)".)
Warfarin is also used in people who have already developed a harmful blood clot, including some people who have had a stroke, heart attack, a clot that has traveled to the lung (pulmonary embolism or PE), or a blood clot in the leg (deep vein thrombosis or DVT).
Warfarin does not dissolve clots, but it keeps them from increasing in size and moving to another part of the body. This allows the body's natural systems to break down a clot over time, and helps reduce the chance of clots developing in people with a higher risk of forming clots. Warfarin prevents and treats serious medical problems caused by blood clots. (See "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)" and "Patient education: Ischemic stroke treatment (Beyond the Basics)" and "Patient education: Pulmonary embolism (Beyond the Basics)".)
WARFARIN MONITORING — The goal of warfarin therapy is to decrease the clotting tendency of blood, but not to prevent clotting completely. Therefore, the blood's ability to clot must be carefully monitored while a person takes warfarin. The dose of warfarin is adjusted to maintain the clotting time within a target range, based on the results of periodic blood tests. These tests can be done in a laboratory or using a portable device at home.
Prothrombin time (PT) — The clotting test used to measure the effect of warfarin is the prothrombin time (called pro time, or PT). The PT is a laboratory test that measures the time it takes for a clot to form. It is measured in seconds. It is particularly sensitive to the clotting factors affected by warfarin. The PT is also used to compute the measure most commonly used to adjust the warfarin dose, known as the INR (or International Normalized Ratio).
International Normalized Ratio (INR) — The INR is a way of expressing the PT in a standardized way by comparing it to a reference value; this ensures that results obtained by different laboratories in different facilities can be compared reliably. It is expressed as a number without units.
The longer it takes the blood to clot, the higher the PT and INR. The target INR range depends upon the clinical situation. In most cases the target INR range will be between 2 and 3, although other ranges may be chosen if there are special circumstances. In a person who is not taking warfarin, the INR would be approximately 1.
If the INR is below the target range (ie, under-anticoagulated), there is an increased risk of clotting. On the other hand, if the INR is above the target range (ie, over-anticoagulated), there is an increased risk of bleeding.
Dosing — The dose of warfarin is adjusted to get the PT/INR blood test into the correct range. The prothrombin time/international normalized ratio (PT/INR) is monitored more often when the dose is being changed, when the person starts or stops another medication, or when his or her medical condition changes. It is monitored less often when the dose is stable. A typical frequency of monitoring for stable dosing is approximately every four or six weeks.
In addition to increased monitoring, changes in your other medications or medical condition may result in the need for a higher or lower daily warfarin dose.
WARFARIN SIDE EFFECTS
Possible side effects — The major complication associated with warfarin is bleeding. This includes serious, life-threatening bleeding such as bleeding into the brain or internal bleeding, which is rare, and minor bleeding such as easy bruising, gum bleeding, or nosebleeds, which are common and can occur with any anticoagulant.
The risk of bleeding is different in different people. Bleeding risk is greatest during the few weeks warfarin is started and during periods of illness. In general, the risk of major internal bleeding is about 1 to 3 percent per year; people who have tolerated warfarin well for at least six months and are on a stable dose of warfarin usually have a risk for major internal bleeding that is closer to 1 percent per year. Excessive bleeding, or hemorrhage, can occur from any area of the body even if the warfarin is having the desired (rather than an excessive) effect, and people on warfarin should report any falls or accidents, as well as signs or symptoms of bleeding or unusual bruising.
●Signs of internal bleeding include severe headache or changes in strength in one part of the body, blood in the urine, bloody or dark stool, or vomiting blood. These signs should prompt immediate discussion with your healthcare provider, who may order a PT/INR test and an in-person evaluation. (See 'When to seek help' below.)
●Minor bleeding includes bleeding from the gums, nosebleeds, or easy bruising. It is important to report changes in the severity or frequency of these symptoms so that your healthcare provider can decide on the appropriate steps to take.
Because the risk of bleeding increases as the INR rises, the INR is closely monitored and adjustments are made as needed to maintain the INR within the target range. (See 'International Normalized Ratio (INR)' above.)
Warfarin can also cause a rare side effect called skin necrosis or gangrene, which can cause dark red or black areas on the skin. This complication is more likely in people with an inherited clotting disorder called protein C deficiency, which is very rare. When it occurs, it is most likely to be seen during the first several days of warfarin therapy.
Warfarin may cause other possible side effects. More detailed information is available in the patient drug information hand-out from Lexicomp, available through UpToDate.
When to seek help — If there are obvious or subtle signs of bleeding, including the following, you should call your healthcare provider immediately.
●Persistent nausea, stomach upset, or vomiting blood or other material that looks like coffee grounds
●Headaches, dizziness, or weakness
●Nosebleeds
●Dark red or brown urine
●Blood in the bowel movement or dark-colored stool
●A serious fall or head injury, even if there are no other symptoms
●A car accident or other serious injury that could cause bleeding
It is also important to notify your healthcare provider if you have any of the following:
●Bleeding from the gums after brushing the teeth
●Swelling or pain at an injection site
●Black and blue skin (bruising)
●Excessive menstrual bleeding or bleeding between menstrual periods
●Diarrhea, vomiting, or inability to eat for more than 24 hours
●Fever (temperature greater than 100.4°F or 38°C), which could be a sign of infection that might alter the INR
●A new medication prescribed by another clinician, because some medications can alter the INR in people taking warfarin
●A planned surgery or procedure, because it may be necessary to stop the warfarin for a period of time to decrease your risk of bleeding during or after the procedure
It is important to remember that warfarin is taken to reduce the risk of a clotting condition(s), such as a deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke. If you develop any symptoms of a clot, seek immediate medical attention. (See "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)" and "Patient education: Pulmonary embolism (Beyond the Basics)" and "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)".)
PREGNANCY AND WARFARIN
Birth defects — Warfarin passes from mother to baby across the placenta and can interfere with normal blood clotting in the baby. Warfarin can also interfere with the formation of bone and cartilage in the developing fetus. These effects on blood clotting and development before birth can lead to birth defects and other problems. A woman who becomes pregnant while on warfarin should notify her healthcare provider immediately. A women taking warfarin who plans to become pregnant should discuss a plan of action with her healthcare provider.
Heparin or low molecular weight heparin (sample brand name: Lovenox) are anticoagulants that do not cross the placenta from mother to baby and can be used instead of warfarin during pregnancy. Warfarin can be restarted after delivery.
Breastfeeding — Although warfarin does not pass into breast milk, a woman who wishes to breastfeed while taking warfarin should consult her healthcare provider. Warfarin is considered safe for use in breastfeeding women and their infants.
OTHER RECOMMENDATIONS
Take warfarin on a schedule — Warfarin should be taken exactly as directed. Do not increase, decrease, or change the dose unless told to do so by a healthcare provider or according to a self-management protocol if you are using an international normalized ratio (INR)-monitoring device at home. If a dose is missed or forgotten, call the prescribing clinician for advice. Sometimes using a pill box (picture 1), a dosing calendar, or a smartphone app can help with taking warfarin doses correctly.
Warfarin tablets come in different strengths. Each is usually a different color, with the amount of warfarin (in milligrams) clearly printed on the tablet. If the color, shape, or dose of the tablet appears different from those taken previously, you should immediately notify your pharmacist or healthcare provider.
Reduce the risk of bleeding — There is a tendency to bleed more easily than usual while taking warfarin. Some simple measures can decrease this risk. Examples of common sense precautions include:
●Always use a seatbelt.
●Wear a helmet when riding a bicycle or motorcycle.
●Avoid using non-prescription medicines that contain a nonsteroidal anti-inflammatory drug ("NSAID") as well as other over-the-counter remedies without discussing with your healthcare provider. (See 'Warfarin and medications' below.)
●When seeing any healthcare provider (doctor, dentist, nurse), tell them you are taking warfarin.
Keep in mind that any injury you get could bleed more than normal. This includes everything from small cuts to the skin (such as nicks from a razor) to more serious injuries. To lower your risk, you can take extra care when doing things that could cause bleeding. This might include shaving with an electric razor rather than a razor blade, being careful when using knives or sharp objects, and avoiding certain contact sports with a high risk of injury. Additional measures some people take include avoiding ice and other slippery surfaces, removing tripping hazards around your home, and reducing the risk of tripping over a pet using aids such as bell collars, obedience training, and two-handed leash holds. Use your clinician as a resource to help you figure out the approaches that work best for you.
Warfarin and food — Some foods and supplements can interfere with warfarin's effectiveness. Consult a healthcare provider before making major dietary changes (eg, starting a diet to lose weight, starting a nutritional supplement or vitamin).
●Vitamin K – The use of warfarin should not interfere with a healthy diet. However, it is important not to have large day-to-day variations in the amount of vitamin K intake from food, because changes in the daily amount of vitamin K intake can alter the INR. People who take warfarin should aim to eat a relatively similar amount of vitamin K-containing foods each week. Moderate daily intake of approximately the same amount of vitamin K is likely to keep the INR more stable. Switching to a lower amount of vitamin K can increase the INR, potentially increasing the risk of bleeding; and switching to a greater amount of vitamin K can lower the INR, potentially increasing the risk of blood clots. Some foods that have a high level of vitamin K include: kale, broccoli, spinach, collard or turnip greens, lettuce, Brussels sprouts, and cabbage (table 1).
●Cranberry juice and grapefruit juice – There have been mixed reports on the effect of cranberry juice or grapefruit juice in people who use warfarin to prevent blood clots. Some clinicians suggest that people taking warfarin not consume more than one or two glasses of either juice per day.
Warfarin and alcohol — Alcohol in low or moderate amounts (one or two servings per day) is unlikely to have major effects on the INR. People who consume alcohol should limit intake to 1 to 2 servings per day. A serving is equal to 1 beer (12 ounces), 1 glass of wine (5 ounces), or 1.5 ounces of spirits. People on warfarin therapy should avoid drinking excessive amounts of alcohol over a short period of time (eg, with a single meal) because this can affect the INR and increase the risk of injury and serious bleeding.
Warfarin and medications — A number of medications, herbs, and vitamins can interact with warfarin. Interactions may change (either increase or decrease) the action of warfarin or the other medication. The warfarin dose may need to be adjusted (up or down) to maintain an optimal anticoagulant effect. Examples of these interactions are provided in the tables (table 2). Other medicines that are not on the table can also interact with warfarin. Any time a new medicine is started or an existing one is stopped, people taking warfarin should have their medications carefully analyzed for possible interactions. This can be done by using the Lexicomp drug interactions program included with UpToDate.
People who take warfarin should consult with their clinician before taking any new medication, including over-the-counter (non-prescription) drugs, herbal medicines, vitamins, supplements, or any other products. Some of the most common over-the-counter pain relievers, including those that contain aspirin or an NSAID such as ibuprofen (sample brand names: Advil, Motrin) or naproxen (sample brand name: Aleve), may increase the risk of bleeding. Acetaminophen (brand name: Tylenol) may interact with warfarin if taken in doses over the recommended maximum of 4000 mg per 24-hour period. If more than one or two doses of a fever reducer or over-the-counter pain medication is needed, acetaminophen is preferable to aspirin or an NSAID.
Some anticoagulation specialists recommend that people avoid taking natural medicines and herbs while on warfarin because the ingredients in these products are not standardized and their effects on INR are unpredictable. However, if you do take a natural product or herbal supplement, more frequent INR monitoring may be necessary to ensure safety. It's a good idea to talk to your healthcare provider before you try any new herbs or supplements.
Wear medical identification — People who require long-term warfarin should wear a bracelet, necklace, or similar alert tag at all times. In addition, a medication wallet card placed next to a driver's license or other official identification can be helpful. If an accident occurs and the person is too ill to explain their condition, this will help responders provide appropriate care.
The alert tag should include a list of major medical conditions and the reason warfarin is needed (eg, atrial fibrillation), as well as the name and phone number of an emergency contact. One device, Medic Alert, provides a toll-free number that emergency medical workers can call to find out a person's medical history, list of medications, family emergency contact numbers, and healthcare provider names and numbers.
CAN I SWITCH TO A DIFFERENT ANTICOAGULANT? — Many people who take warfarin wonder if they could switch to one of the anticoagulants that do not require regular blood test monitoring. Medicines in this group are called direct oral anticoagulants (DOACs). These medications include dabigatran (brand name: Pradaxa), rivaroxaban (brand name: Xarelto), apixaban (brand name: Eliquis), and edoxaban (brand names: Savaysa, Lixiana) (table 3).
These medicines are not monitored with regular blood tests, and in many people, they may be more effective and safer than warfarin (less risk of bleeding). However, these medicines are not the best choice for everyone. For example, warfarin is used for people with a mechanical heart valve. Every medication has risks and benefits, and the best choice for you depends on your individual situation. Ask your doctor if you have concerns or questions about which anticoagulant you should take.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Deep vein thrombosis (blood clot in the legs) (The Basics)
Patient education: Taking care of bruises (The Basics)
Patient education: Pulmonary embolism (blood clot in the lungs) (The Basics)
Patient education: Prosthetic valves (The Basics)
Patient education: Choosing a medicine for blood clots (The Basics)
Patient education: Taking medicines for blood clots (The Basics)
Patient education: Factor V Leiden (The Basics)
Patient education: Prothrombin time (PT) test and International Normalized Ratio (INR) (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Atrial fibrillation (Beyond the Basics)
Patient education: Antiphospholipid syndrome (Beyond the Basics)
Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)
Patient education: Ischemic stroke treatment (Beyond the Basics)
Patient education: Pulmonary embolism (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Warfarin and other VKAs: Dosing and adverse effects
Biology of warfarin and modulators of INR control
Management of warfarin-associated bleeding or supratherapeutic INR
Overview of vitamin K
Clinical use of coagulation tests
Risks and prevention of bleeding with oral anticoagulants
The following organizations also provide reliable health information.
●National Library of Medicine
(https://medlineplus.gov/healthtopics.html)
●National Heart, Lung, and Blood Institute
●National Institute of Neurological Disorders and Stroke
●United States Food and Drug Administration
(https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm)
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ACKNOWLEDGMENT — UpToDate would like to acknowledge Karen A Valentine, MD, PhD, who contributed to earlier versions of this topic review.
