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Anticoagulants

Blood Thinners

About

About anticoagulants

Anticoagulants are nonhabit-forming medications that are used to treat and prevent vascular diseases caused by blood clots. Under normal conditions, blood should not clot unless the body has been injured. However, there are conditions, such as atherosclerosis and venous diseases, that cause blood clots to form even when a person has not been wounded. These blood clots can be dangerous if they are large enough to block a blood vessel (a thrombus), or if either a whole clot or pieces of the clot break off, travel through the bloodstream, and block a blood vessel in another part of the body (an embolism). Either of these situations could lead to heart attack or stroke. Therefore, anticoagulants may be prescribed to reduce the risk of these dangerous events.

Anticoagulants prescribed for regular use (e.g., warfarin) are generally vitamin K antagonists taken in pill form. Vitamin K is an essential cofactor in the blood clotting process. They typically take effect within 48 hours, but may take a week or longer to be stabilized. Other anticoagulants (e.g., herparin, fibrin and thrombin inhibitors) are administered through intravenous (I.V.) injection in a medical setting, where they quickly take effect. Patients will sometimes be given anticoagulants in both forms when first beginning anticoagulant treatment and will then continue to take only the vitamin K inhibitors by mouth.

Types

Types and differences of anticoagulants

Anticoagulant medications include:


  • acenocoumarol
  • argatroban
  • anisindione
  • ardeparin
  • bivalirudin
  • dalteparin
  • danaparoid
  • dicumarol
  • enoxaparin
  • fondaparinux
  • heparin
  • hirudin
  • razaxaban
  • warfarin

The two standard anticoagulants used are heparin and warfarin. These two medications act somewhat differently to accomplish the same thing: inhibiting the growth of existing blood clots or preventing the formation of new ones.

Studies find that even low-dose warfarin, an oral medication that acts by inhibiting blood clotting factors that depend on vitamin K, can be effective in reducing the risk of recurrence of blood clots, especially in patients with a history of deep vein thrombosis and previous heart attack. This also applies to those at risk of deep vein thrombosis, including patients undergoing hip or leg surgery.

Heparin, by contrast, acts by indirectly inhibiting thrombin, a component of blood that is critical to clotting. Newer forms of heparin, called low-molecular-weight heparin, have been developed that are more predictable in their anticoagulant effect and do not need to be monitored in a therapeutic setting.

However, both warfarin and heparin have drawbacks that have prompted researchers to search for new anticoagulants. The two largest drawbacks are their relatively narrow window of effectiveness before the risk of bleeding, and their highly variable nature among individuals. Typically, anticoagulation therapy has required very close laboratory monitoring as physicians attempt to walk the fine line between adequate anticoagulation and an elevated risk of bleeding.

Newer anticoagulants are being studied. In general, these medications act in a similar fashion to heparin or warfarin, but are hopefully more predictable and do not require close laboratory monitoring. Some of the newer anticoagulants include:


  • Danaparoid. This anticoagulant is frequently used in patients with deep vein thrombosis. It is closely related to heparin. Because of its high cost and other drawbacks, this medication is no longer offered in the United States by its manufacturer.
  • Hirudin, argatroban and bivalirudin. These anticoagulants are direct thrombin inhibitors. They have been studied for the treatment of deep vein thrombosis, prevention of stroke in patients with atrial fibrillation, and among patients with unstable angina or recent heart attack. Bivalirudin may also be used to help prevent bleeding after coronary angioplasty. These agents are usually used when heparin cannot be used due to heparin-induced thrombocytopenia.
  • Fondaparinux and idraparinux. A synthetic version of heparin that works by inhibiting a different part of the clotting process. A longer–acting form, which can be given only once a week, is currently in clinical trials.
  • Razaxaban. This anticoagulant can be administered orally and is currently being studied for its usefulness in preventing deep vein thrombosis in patients undergoing knee replacement surgery.
Hot It Works

Normal body response to injury

To understand how various anticoagulants work, it is important to understand the body’s normal reaction to a cut or injury that involves blood loss. After a cut, a chain of events begins that will rapidly seal the wound and reduce the loss of blood. This chain includes:


  • Vasoconstriction. The blood vessels narrow, restricting the amount of blood lost.
  • Platelet aggregation. Platelets, also known as thrombocytes, play a major role in blood coagulation, clotting and hemostasis (stoppage of bleeding). When a small blood vessel is injured, platelets begin to stick to each other and to the sides of the injured tissue and form a plug, which becomes covered with strands of thread-like fibrin. Soon the blood clot (plug) shrinks in place and blocks any further loss of blood. Platelets also release chemicals that begin the healing process. Without this important clotting function of the platelets, excessive and potentially life-threatening amounts of blood would be lost after simple cuts or scrapes. Antiplatelets (e.g., clopidogrel) are medications that inhibit blood clotting by reducing the platelets’ stickiness.
  • Blood coagulation (or plasma factors). Plasma is the liquid part in which the blood cells are suspended. Blood coagulation occurs due to a series of reactions in plasma. Scientists have identified more than 13 distinct chemical reactions that result in clot formation. Anticoagulant medications affect these processes in one of two ways:
    • Vitamin K antagonists. For several of the plasma reactions, vitamin K serves as a catalyst, which speeds the reactions. Some medications can inhibit vitamin K’s ability to activate these clotting factors and therefore prevent or lessen blood coagulation.
    • Fibrin and thrombin inhibitors. Some medications can inhibit the production of these chemicals in the blood and therefore prevent or lessen coagulation of the blood.
Conditions

Conditions treated

Anticoagulants are prescribed to prevent the formation of blood clots in high-risk patients or to limit the growth of existing clots. Larger clots are more prone to falling apart and forming emboli – pieces of clots that break off and travel to other areas of the body. If these traveling clots become lodged in a blood vessel, the resulting embolism could be fatal. Anticoagulants are commonly prescribed for people with the following conditions, or who have undergone certain medical procedures. These include:


  • Deep vein thrombosis. One or more blood clots in veins embedded deeply in the muscle mass of the legs or lower abdomen. Patients with this condition are at great risk for developing pulmonary emboli.
  • Pulmonary embolism. A blockage in the blood vessels of the lungs, which is caused by a blood clot that has broken away from its original location and traveled through the bloodstream to the lungs, often as the result of deep vein thrombosis.
  • Coronary artery disease with unstable angina. This is a condition in which hardening and narrowing of the arteries (atherosclerosis) causes unpredictable episodes of chest pain, pressure or discomfort. In contrast, stable angina is usually triggered by a predictable event, such as exercise.
  • Certain types of heart attacks. Anticoagulants are a primary treatment of certain types of heart attacks, which are life-threatening events that result in permanent heart damage or death.
  • Atrial fibrillation. A rapid, irregular heart rhythm (arrhythmia) caused by faulty electrical signals from the upper chambers of the heart (atria). This arrhythmia causes blood clots to form in the left atrium. If these blood clots travel out of the heart and to the brain, they could cause a stroke.
  • Cerebral thrombosis. The formation of an obstructing blood clot (thrombus) in a blood vessel within the brain. This increases the risk of a stroke or mini-stroke (transient ischemic attack).
  • Valvular heart disease. Any dysfunction or abnormality of one or more of the heart’s four valves. Anticoagulants are prescribed for patients who have both valvular heart disease and atrial fibrillation. They are also prescribed for every patient with a mechanical valve.
  • Cardiomyopathy. Anticoagulants are sometimes used to treat this disease of the heart muscle.
  • Balloon angioplasty. A procedure in which the physician inflates a balloon at the tip of a catheter to press plaque back against the artery wall to widen the vessel and make room for blood to flow. An angioplasty is used to treat both heart attacks and angina, and anticoagulants are often prescribed for patients who have recently undergone this procedure.
  • Open-heart surgery. An operation in which the chest and (sometimes) the heart are opened surgically while the entire blood flow is diverted through a heart-lung machine.

Conditions of concern

Patients should talk to their physician before taking anticoagulants if they have been diagnosed with any of the following conditions, because the medication could potentially lead to uncontrolled bleeding:


  • Infections of the heart (e.g., bacterial endocarditis).
  • Vitamin K deficiency. Patients with this deficiency may still be prescribed warfarin but at a very low dose. It is very important for patients on anticoagulants to maintain a fairly consistent level of vitamin K in their diet.
  • Bleeding disorders.
  • Past or current ulcer (stomach or duodenal). Ulcer patients are often prescribed anticoagulants after the risks and benefits have been discussed with their physician. Although a past history of gastrointestinal bleeding rarely interferes with taking the medications, patients who have current gastrointestinal bleeding cannot take them.
  • Aneurysm (swelling or bulging in part of the wall of a blood vessel). Anticoagulants can be used with caution in patients with certain types of aneurysms.
  • Cancer of the internal organs. Certain cancers can cause bleeding.
  • Recent surgery or spinal anesthesia.
  • Pregnancy. Pregnant women cannot take warfarin but can take other anticoagulants, such as heparin.
Side effects

Potential side effects

Possible side effects of coagulants include:


  • Unusual bleeding (gastrointestinal, urinary tract, etc.)
  • Osteoporosis
  • Cloudy, red or dark urine
  • Allergic reaction
  • Fever or chills
  • Skin necrosis, or death, usually located on the extremities, including the breasts, trunk and penis in males
  • Blue or purple toes
  • Edema (swelling) of eyelids, face or lips
  • Congenital defects of the fetus when administered during pregnancy

Coumadin paradox is a rare condition which may occur early (within three days) of adminstration of the anitcoagulant warfarin (coumadin). The condition is associated with increased tendency to form blood clots. To avoid this condition, heparin can be adminstered together with warfarin because its action is immediate. When the anticoagulant effect of warfarin is evident, heparin can be discontinued.

Up to 5 percent of individuals taking heparin may develop heparin-induced thrombocytopenia (HIT), or delayed-onset HIT – reactions that can increase the risk of the formation of new clots. Research is ongoing in the development of “antidotes” that can be given to counter the effects of this complication. Some of the newer anticoagulants being developed may reduce the risk of this condition.

Interactions

Drug or other interactions

Patients should talk to their physician before taking any other medication (either prescription or over-the-counter), nutritional supplements or herbal remedies. These and other substances may slow the rate at which anticoagulants are removed from the body, increasing the risk of overdose or the risk of bleeding. The effectiveness of anticoagulants may also be decreased by some substances because a huge number of drugs can interact with them (especially warfarin). Of particular concern are:


  • Antibiotics. Medications that prevent or treat bacterial infection.
  • Other anticoagulants.
  • Vitamin K supplements.
  • Some anti-inflammatory medications.
  • Some analgesics (pain medications), including nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Some ulcer medications.
  • Some antiarrhythmics. Medications used to treat arrhythmias (abnormal heart rhythms).
  • Asthma medications.
  • Some over-the-counter medications, including those used to treat indigestion.
  • Grapefruit juice.

Other substances that may adversely react with anticoagulants include (but are not limited to) alcohol, barbiturates, caffeine, nicotine and marijuana.

How to use

Lifestyle considerations

When first taking anticoagulants, patients should avoid operating heavy machinery (e.g., driving) until they know how the medication may affect them. Patients should remember that anticoagulants can control many conditions, but do not cure them. Patients should continue to take their medication exactly as directed and to keep all scheduled follow-up appointments with their physician.

Especially at the beginning of therapy, patients taking anticoagulants need to undergo regular blood tests to monitor their dosage. These tests usually require the patient to visit a hospital, physician’s office or laboratory regularly. Newer devices allow patients to monitor their medication at home.

Patients on anticoagulants need to avoid cutting themselves, including when shaving, brushing their teeth (a soft toothbrush is recommended) or flossing, because their blood will not clot as effectively. Similarly, patients are advised against playing contact sports (e.g., football) or any other activity where there is risk of injury (e.g., skiing or motorcycle riding).

Vitamin K plays an integral role in blood clot formation and inhibits the action of anticoagulant medications. Dosages of these medications will therefore depend on the levels of vitamin K in the patient’s diet. Patients should not make any changes to their diet that would greatly increase or decrease their levels of vitamin K intake without consulting with their physician, who may need to alter the dosage of the anticoagulants. Vitamin K is most prevalent in green leafy vegetables (including spinach, broccoli, cabbage, kale and lettuce) and some vegetable oils.

Care should also be exercised in patients with Factor V (five) Leiden. This is a variation in a gene that affects the clotting process, increasing coagulation. Factor V Leiden is the most common inherited blood disorder in the United States. It is present in 4 to 6 percent of Caucasians; 2 percent of Hispanic Americans; a little over 1 percent of African Americans and Native Americans and about 0.5 of one percent of Asian Americans. Treatment is typically unwarranted unless there is evidence of a blood clot, in which case warfarin or other anticoagulants are prescribed. Depending on the situation, anticoagulants may be recommended to help afford advance protection against the development of blood clots. For example, women with a Factor V Leiden mutation may be advised to take anticoagulants during pregnancy and in the postpartum period.


Pregnancy use issues

Warfarin use during pregnancy is not recommended because it may cause birth defects. In addition, use during the last six months of pregnancy may cause severe bleeding in the fetus and, in the last two weeks of pregnancy, may cause bleeding in both the fetus and the mother. However, heparin is routinely prescribed for pregnant women who have mechanical valves.

Some anticoagulants pass into nursing babies through breast milk. Physicians may monitor nursing infants to detect any unwanted effects or prescribe a medication that would overcome those effects. Patients should consult their physician about breast-feeding when taking anticoagulants.


Child use issues

There is no indication that the risk of side effects from anticoagulants is different in children than in adults. However, infants may be more susceptible to vitamin K antagonists because of a vitamin K deficiency. Parents need to discuss the potential risks and benefits with a pediatrician before consenting to anticoagulant treatments in their children.


Elderly use issues

Older adults are more susceptible to the effects of anticoagulants and have a higher risk of hemorrhage. Generally, older patients require lower doses of anticoagulants and careful monitoring.

Symptoms of medication overdose

The most common side effect of anticoagulants is bleeding. Patients should notify their physician immediately if they notice any unusual bleeding. Symptoms of internal bleeding include:


  • Abdominal pain or swelling
  • Black stools
  • Blood in stools, urine or vomit or when coughing
  • Blurred vision or bleeding in eyes
  • Chest pain
  • Confusion
  • Dizziness or lightheadedness
  • Nausea or vomiting
  • Headache
  • Joint stiffness, swelling (edema) or pain
  • Fainting (syncope)
  • Sudden weakness
  • Shortness of breath
  • Numbness or paralysis of the arms, legs or face

Questions for your doctor

Patients may wish to ask their doctor the following anticoagulant-related questions:
  1. How long will I need to take this medication?
  2. Should I take it with or without food?
  3. How often will I need monitoring to determine if the level of anticoagulation is satisfactory?
  4. What should I do if I miss a dose?
  5. Do I need to wear a bracelet or any other ID to let medical personnel know that I'm on anticoagulants?
  6. What emergency measures are available in the event of a bleeding incident?
  7. Are there cheaper or generic versions of this drug available?
  8. Are there are foods I should avoid besides grapefruit? What about other citrus?
  9. Will this drug interfere with my exercise program?
  10. Will this drug affect menstruation?

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