Anticoagulants

An anticoagulant is a drug (blood thinner) that treats, prevents, and reduces the risk of blood clots-breaking off and traveling to vital organs of the body, which can lead to life threatening situations. They work by preventing blood from coagulating to form a clot in the vital organs such as the heart, lungs, and brain.

For example, a DVT or deep vein thrombosis (blood clot in the leg or lower extremity) can happen if you have a medical condition that keeps you immobile or if you have been sitting for n long period of time without getting up and stretching, like traveling by plane, car, or train. If the clot breaks off from the vein or artery of a leg it can get lodged in the blood vessels of the lung where it can form a clot in the lung (pulmonary embolism). This is a life threatening medical condition. Similarly, a stroke can be caused by a clot lodged in a vessel in the brain.

Anticoagulant treatment is used to prevent the formation of new blood clots, and to treat existing clots by preventing them from growing larger in size. It also reduces the risk of embolization of blood clots to other vital organs such as the lungs and brain.

An anticoagulant medicine is used in patients to prevent blood clots from forming in veins, arteries, the heart, and the brain of a patient. For example, if the clot travels to the patient's heart it can cause a heart attack or if one forms in the brain it may cause a stroke or TIA (mini-stroke, transient ischemic attack).

Examples of diseases and health conditions that require treatment with anticoagulants to reduce the risk of clots forming, or are used to prevent life-threatening problems include:

• Deep vein thrombosis (DVT)
• Heart attack
• Stroke
• For the prevention or treatment of:
• Pulmonary embolism
• Blood clots within venous and arterial catheters
• Stent thrombosis
• Blood clots during atrial fibrillation (afib) treatment

The most common side effect of treatment with anticoagulant medicine is bleeding. Treatment with these products may cause various degrees of bleeding, including fatal bleeds.

This list of adverse effects associated with anticoagulants are compiled from adverse effects listed for various anticoagulants and may not apply to every medicine.

Common side effects include:

• Bleeding
• Abdominal pain
• Flatulence (intestinal gas)
• Headache
• Lethargy
• Dizziness
• Fever
• Local injection site reactions
• Nausea
• Anemia
• Bruises caused by trauma (ecchymosis)
• Diarrhea

Other side effects include:

• Hair loss (alopecia)
• Rash
• Itching (pruritus)
• Changes is sense of taste
• Fainting (syncope)
• Shortness of breath
• Low blood pressure (hypotension)
• Chest pain

Serious side effects include:

• Cholesterol embolus syndrome
• Intraocular hemorrhage
• Groin hemorrhage
• Tissue necrosis
• Hematuria
• Anemia
• Hepatitis
• Respiratory tract bleeding
• Hypersensitivity reaction
• Hemorrhagic stroke
• "Purple toe" syndrome
• Increased fracture risk with long-term usage
• Calciphylaxis
• Elevation of serum aminotransferases
• Thrombocytopenia

Treatment with more than one blood thinner or using medicine that can cause bleeding will increase the risk of bleeding from any anticoagulant. Examples of drugs that also can cause bleeding when they interact include:

• Antiplatelet medicine such as aspirin and other nonsteroidal anti-inflammatory medications (for example, ibuprofen [Motrin], naproxen [Aleve]), clopidogrel (Plavix), and prasugrel (Effient)
• Serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and paroxetine (Paxil).
• Garlic and ginkgo also increase the risk of bleeding when combined with another medicine that thins the blood because these herbs can cause bleeding when taken alone.
• Drug and herbal supplement interactions with warfarin

Several drugs may increase or decrease the anticoagulant effect of warfarin (Jantoven) therapy. Drugs that increase warfarin's anticoagulating effect by reducing its breakdown include:

• amiodarone (Cordarone)
• trimethoprim/sulfamethoxazole (Bactrim)
• fluconazole (Diflucan)
• itraconazole (Sporanox)
• fluvastatin
• fluvoxamine
• metronidazole miconazole
• voriconazole (Vfend)
• zafirlukast (Accolate)
• ciprofloxacin (Cipro)
• cimetidine
• atorvastatin (Lipitor)
• clarithromycin (Biaxin)
• fluoxetine (Prozac)
• indinavir (Crixivan)
• ritonavir (Norvir)

Some drugs and herbal products that may reduce the anticoagulating effect of warfarin by increasing its breakdown include:

• St. John's wort
• carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol)
• rifampin, bosentan (Tracleer)
• prednisone

Use of warfarin with foods high in Vitamin K

Foods with high vitamin K content (for example, green leafy vegetables) reduce the anticoagulant effect of warfarin. It's important for patients to try to consume a consistent amount of vitamin K containing foods to avoid fluctuations in the effect of warfarin. A patient that regularly consumes high vitamin K containing foods may require a higher dose of warfarin (Jantoven) to achieve the desired level of anticoagulation.

No. Anticoagulants and antiplatelets differ in how they work. Anticoagulants prevent blood coagulation by reducing the action of clotting factors directly or indirectly. Antiplatelets work by inhibiting the ability of platelets to participate in the clotting process. Aspirin is an example of an antiplatelet medication.

Anticoagulation therapy is not recommended for patients with certain diseases or health conditions because they increase the risk of bleeding. Patients who have any of the following health problems or are pregnant shouldn't use this type of therapy.

• Hemophilia or another bleeding disorder
• Are pregnant
• High risk of bleeding in the brain (hemorrhagic stroke)
• Cerebral aneurysm
• Dissecting aorta
• Pericarditis
• Pericardial effusion
• Bacterial endocarditis
• Active ulceration
• An active bleed
• Are undergoing surgery

There are different types of anticoagulants, and they are classified by how they affect the normal coagulation pathway (see the mechanism of action section). The different classes are:

1. Vitamin K antagonists (coumarin anticoagulants)
2. Low molecular weight heparins (LMWH)
3. Direct thrombin inhibitors
4. Factor Xa Inhibitors

Vitamin K antagonists

• warfarin (Coumadin, Jantoven) – oral tablets

Low molecular weight heparins (LMWH) and heparin (vials and syringes)

• enoxaparin (Lovenox)
• dalteparin (Fragmin)
• heparin

Thrombin inhibitors

• bivalirudin (Angiomax) – powder for injection
• argatroban (Acova) - injection
• dabigatran (Pradaxa) – oral capsule
• antithrombin III (Thrombate III) – powder for injection

Factor Xa Inhibitors (These are relatively new anticoagulants)

• apixaban (Eliquis) – oral tablets
• fondaparinux (Arixtra) - injection
• rivaroxaban (Xarelto) – oral tablets
• edoxaban (Savaysa) – oral coated tablets

• Most anticoagulants have not been adequately studied in patients who are pregnant because clinical trials exclude them. Therefore, this type of therapy generally is avoided during pregnancy and should be used during pregnancy only if the potential health benefit justifies the potential dangers to the fetus.
• Warfarin, specifically, is a medication that should be avoided if you are pregnant or are planning to become pregnant. Birth defects and fetal bleeding have been reported during this type of therapy when taken during pregnancy. Be careful to not get pregnant if you are currently on this type of therapy. If you do become pregnant or are trying to conceive contact your doctor immediately.
• Enoxaparin is an anticoagulant medicine that does not cross the placenta and shows no evidence of effects on the fetus. It is often recommended by doctors for patients who are pregnant as an alternative to oral therapy with warfarin, which cannot be safely used during pregnancy.
• There is little data about the excretion of this medicine in breast milk. Available evidence suggests that warfarin is not secreted in breast milk. Since most medicines are excreted in breast milk, medical experts generally recommended that if you are receiving this type of therapy you should not breastfeed.

How vitamin K antagonists (warfarin) cause anticoagulation

• Warfarin prevents the formation of a blood clots in patients by reducing the production of factors II, VII, IX, and X, and the anticoagulant proteins C and S by the liver. These factors are involved in the body's natural clotting process. The production of these factors by the liver are dependent on adequate amounts of vitamin K. Warfarin reduces the production of the factors because it antagonizes vitamin K. The dose of warfarin is carefully adjusted to achieve optimal anticoagulation while minimizing the risk of bleeding.

How low molecular weight heparins (LMWH) and heparin cause anticoagulation

• Heparin and low molecular weight heparins prevent a blood clot from forming by blocking the action of two of the 12 clot-promoting proteins in the blood (factors X and II) whose action is necessary for blood to clot. Low molecular weight heparins are produced by chemically breaking heparin into smaller-sized molecules. Unlike heparin, medical professionals do not monitor the effect of low molecular weight heparins with blood tests and the dose of a low molecular weight heparin is not titrated.

How thrombin inhibitors cause anticoagulation

• Thrombin inhibitors work by blocking the action of thrombin, a protein that is necessary for the coagulation of blood and the formation of a blood clot. Reducing the action of thrombin reduces the ability of blood to clot.

How factor Xa inhibitors cause anticoagulation

• Factor Xa inhibitors are novel anticoagulants. They block the action of factor Xa which is an important protein in the coagulation cascade that causes blood to clot. Reducing the action of factor Xa reduces the ability of blood to clot.

Preparations

Drugs in this class are available as tablets, capsules, powder for injection, prefilled syringes, and in vials containing a solution for injection. Some intravenous anticoagulants (for example, bivalirudin, and heparin) are administered via an intravenous infusion while receiving medical care in the hospital.

Storage

Oral anticoagulants are stored at room temperature. Prefilled syringes and multiple dose vials of low molecular weight heparins, and heparin vials are also stored at room temperature.