Warfarin

Definition

Wafarin is a vitamin K antagonist that belongs to the family of drugs called anticoagulants ("blood thinners, " although it does not actually thin the blood). The brand name of warfarin in the U.S. is Coumadin.

Purpose

Wafarin is used to decrease the clotting ability of the blood and to help prevent harmful clots from forming in the blood vessels. It is also used for the long-term treatment of thromboembolic disease, a common side effect of cancer.

One of the most common hematological complications is disordered coagulation. Approximately 15% of all cancer patients are affected by thromboembolic disease, and it is the second leading cause of death for cancer patients. However, thromboembolic disease may represent only one of many complications in end-stage patients. Thromboembolic disease includes superficial and deep vein thrombosis, pulmonary embolism, thrombosis of venous access devices, arterial thrombosis, and embolism. The cancer itself or cancer treatments may induce coagulation. For example, tamoxifen , a drug prescribed to treat breast cancer , increases the chance of developing pulmonary embolism or deep vein thrombosis.

Cancer and its treatment can affect all three causes of thromboembolic disease including the alteration of blood flow, damage to the cells in blood vessels (endothelial cells), and enhancing procoagulants (precursors, such as fibrinogen or prothrombin, that mediate coagulation). Cancer can affect blood flow by mechanically affecting blood vessels close to a tumor. In addition, tumors cause angiogenesis, which may create complexes of blood vessels with a disordered appearance and flow (varying in magnitude and direction). Chemotherapy or tumors may directly damage endothelial cells. Procoagulants may be secreted into the blood stream by cancer cells or can be increased on the surface of cancer cells.

Description

Warfarin will not dissolve an existing blood clot, but it may prevent it from getting larger. When warfarin is taken orally, it is absorbed quickly from the gastrointestinal tract. It reaches a maximal plasma concentration in 90 minutes and stays in the bloodstream (i.e. its half-life) 36-42 hours. Warfarin circulates in the bloodstream attached to plasma proteins—in particular, a protein called albumin. The response or effects of a warfarin dose vary from person to person.

Whether anticoagulants like wafarin may also improve cancer survival rates independent of their effect on thromboembolism has been investigated. There is suggestive evidence that warfarin may actually enhance cancer survival rates. Animal studies show that warfarin and other agents such as heparin , fibrinolytics, and even antiplatelet agents inhibit tumor growth and metastasis .

Recommended dosage

A doctor may prescribe a dosage based on laboratory blood tests that determine a patient's clotting time. This blood test (called prothrombin time) is conducted usually weekly or monthly as suggested by a physician and should always be done at the same time of day. Based on the clotting time, the doctor determines the dose and/or whether the dose should be adjusted. Warfarin is normally prescribed to be taken once a day, and it should be taken at the same time every day.

Precautions

Following certain precautions when taking warfarin may reduce the risk of side effects and improve the effectiveness of the medication. The rate of blood clotting is affected by illness, diet, medication changes, and physical activities. If an individual has other medical problems, this may affect the use of warfarin. Of particular importance are bleeding ulcers, heavy menstrual periods, infections, high blood pressure, and liver or kidney problems. The doctor should be informed of any changes in these conditions so dose alterations can be made, if necessary. If a patient using warfarin is scheduled for surgery or dental work, the doctor or dentist should be informed that the patient is taking this medication. Warfarin should not be prescribed if an allergic reaction has occurred in the past, during pregnancy or while breastfeeding, or if pregnancy is planned. Anyone taking warfarin should exercise extra care not to cut him/herself and not to sustain injuries that can result in bruising or bleeding.

In addition, patients taking warfarin should watch their intake of vitamin K, since too much vitamin K may alter the way in which warfarin works. The amount of foods high in vitamin K (such as broccoli, spinach, and turnip greens) eaten each week should be kept stable. Grapefruit juice should be avoided because it may intensify the effects of this medication. Alcohol should also be avoided while taking warfarin because it interferes with warfarin's effectiveness.

In order to determine a safe and effective dose, regular blood tests to check prothrombin time should be done while taking this medicine. Individuals taking warfarin frequently require dose adjustments.

Side effects

The most common complication of long-term warfarin therapy is bleeding. The intensity of anticoagulant therapy, age, kidney function, and unidentified diseases of the gastrointestinal and genitourinary tracts all directly influence the risk of bleeding. Patients taking warfarin should be aware of the signs and symptoms that may indicate a bleeding problem. These signs and symptoms include:

• bleeding from the gums or nose
• red or black bowel movements
• coughing up blood (hemoptysis )
• heavy bleeding from cuts or wounds that will not stop
• unusually heavy menstrual bleeding
• blood in the urine
• easy bruising or purple spots on the skin
• severe headache

The patient should inform his/her doctor immediately if any of these symptoms is present.

Other side effects that may occur with warfarin treatment include:

• mild stomach cramps
• upset stomach
• hair loss (alopecia )
• poor appetite (anorexia )
• cough or hoarseness
• fever or chills
• skin rash, hive, or itching
• painful or difficult urination

The occurrence of any of these side effects should also be reported to the doctor.

Interactions

Some medications should not be combined. The patient should check with the doctor monitoring the warfarin treatment before taking any new medication, including over-the-counter medication or medication prescribed by another doctor.

Among the medications and dietary supplements that may alter the way warfarin works are:

• other prescription medications
• nonprescription medications such as aspirin or nonsteroidal anti-inflammatory drugs (i.e. ibuprofen)
• cough or cold remedies
• herbal products and nutritional supplements
• products containing vitamin K

See Also Low molecular weight heparin

Crystal Heather Kaczkowski, MSc.

KEY TERMS

Angiogenesis

—The formation of new blood vessels that occurs naturally under certain circumstances, for example, in the healing of a cut.

Anticoagulant

—A medication that prevents the formation of new blood clots and keeps existing blood clots from growing larger.

Arterial thrombosis

—A condition characterized by a blood clot in an artery.

Blood clot

—A clump of blood that forms in or around a vessel as a result of coagulation. The formation of blood clots when the body has been cut is essential because without blood clots to stop the bleeding, a person would bleed to death from a relatively small wound.

Coagulation

—The blood's natural tendency to clump and stick.

Embolism

—An obstruction in a blood vessel due to a blood clot or other foreign matter that gets stuck while traveling through the bloodstream.

Embolus

—A blood clot, gas bubble, piece of tumor tissue, or other foreign matter that moves through the bloodstream from its site of origin to obstruct a blood vessel.

Endothelial cells

—The cells lining the inside of blood vessels.

Fibrinolytics

—Agents that decompose fibrin, a protein produced in the clotting process.

Pulmonary embolism

—A blockage of the pulmonary artery by foreign matter such as a blood clot.

Thromboembolic disease

—A condition in which a blood vessel is obstructed by an embolus carried in the bloodstream from the site of formation.

Thrombosis

—A condition in which a clot develops in a blood vessel.

Vein thrombosis

—A condition characterized by a blood clot in a vein.

warfarin 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin: a coumarin derivative used as a synthetic anticoagulant both therapeutically in clinical medicine and, in lethal doses, as a rodenticide (see pesticide).

Warfarin A chemical which antagonizes the action of vitamin K; used to reduce blood clotting in people at risk of thrombosis and, at much higher doses, as a rat and mouse poison.

warfarin (wor-fer-in) n. an anticoagulant used mainly in the prevention and treatment of deep vein thrombosis and pulmonary embolism and to prevent embolism in other patients at risk. It is given by mouth; the principal adverse effect is local bleeding. Trade name: Marevan.