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Anticoagulant

Anticoagulant

Overview
An anticoagulant is a substance that prevents coagulation; that is, it stops blood
Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....

 from clotting. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood...

 disorders. Some chemical compounds are used in medical equipment, such as test tube
Test tube
A test tube, also known as a culture tube or sample tube, is a common piece of laboratory glassware consisting of a finger-like length of glass or clear plastic tubing, open at the top, usually with a rounded U-shaped bottom...

s, blood transfusion
Blood transfusion
Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery...

 bags, and renal dialysis equipment.

Anticoagulants are given to people to stop thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood...

 (blood clotting inappropriately in the blood vessels).
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Encyclopedia
An anticoagulant is a substance that prevents coagulation; that is, it stops blood
Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....

 from clotting. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood...

 disorders. Some chemical compounds are used in medical equipment, such as test tube
Test tube
A test tube, also known as a culture tube or sample tube, is a common piece of laboratory glassware consisting of a finger-like length of glass or clear plastic tubing, open at the top, usually with a rounded U-shaped bottom...

s, blood transfusion
Blood transfusion
Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery...

 bags, and renal dialysis equipment.

As medications


Anticoagulants are given to people to stop thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood...

 (blood clotting inappropriately in the blood vessels). This is useful in primary and secondary prevention of deep vein thrombosis
Deep vein thrombosis
In medicine, deep vein thrombosis is the formation of a blood clot in a deep vein...

, pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...

, myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, is the interruption of blood supply to part of the heart, causing some heart cells to die...

s and stroke
Stroke
A stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...

s in those who are predisposed.

Coumarines (Vitamin K antagonists)


The oral anticoagulants are a class of pharmaceuticals
Pharmacology
Pharmacology is the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals...

 that act by antagonizing the effects of vitamin K
Vitamin K
Vitamin K denotes a group of lipophilic, hydrophobic vitamins that are needed for the posttranslational modification of certain proteins, mostly required for blood coagulation...

. Examples include warfarin
Warfarin
Warfarin is an anticoagulant. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed...

. It is important to note that it takes at least 48 to 72 hours for the anticoagulant effect to develop fully. In cases when any immediate effect is required, heparin
Heparin
Heparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...

 must be given concomitantly. Generally, these anticoagulants are used to treat patients with deep-vein thrombosis (DVT), pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...

 (PE), atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia and involves the two upper chambers of the heart. Its name comes from the fibrillating of the heart muscles of the atria, instead of a coordinated contraction...

 (AF), and mechanical prosthetic heart valves.

Adverse effects


Patients aged 80 years or more may be especially susceptible to bleeding complications with a rate of 13 bleeds per 100 person-years.

These oral anticoagulants are used widely as poisons for mammalian pests, especially rodents. (For details, see rodenticide and warfarin
Warfarin
Warfarin is an anticoagulant. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed...

.)

Depletion of vitamin K by coumarine therapy increases risk of arterial calcification and heart valve calcification, especially if too much vitamin D is present.

Available agents

  • Warfarin
    Warfarin
    Warfarin is an anticoagulant. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed...

     (Coumadin) This is the main agent used in the U.S. and UK
  • Acenocoumarol
    Acenocoumarol
    Acenocoumarol is an anticoagulant that functions as a vitamin K antagonist . It is a derivative of coumarin and is marketed under the brand names Sintrom and Sinthrome....

     and phenprocoumon
    Phenprocoumon
    Phenprocoumon is an anticoagulant drug, a derivative of coumarin. It is a vitamin K antagonist that inhibits coagulation by blocking synthesis of coagulation factors II, VII, IX and X. It is used for the prophylaxis and treatment of thromboembolic disorders ....

     This is used more commonly outside the U.S. and the UK
  • Brodifacoum
    Brodifacoum
    Brodifacoum is a highly lethal anticoagulant poison. In recent years, it has become one of the world's most widely used pesticides. It is typically used as a rodenticide but is also used to control larger mammalian pests such as possum....

     Rat poison, not used medically
  • Phenindione
    Phenindione
    Phenindione is an anticoagulant which functions as a Vitamin K antagonist.Hypersensitivity has been observed....


Heparin and derivative substances


Heparin
Heparin
Heparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...

 is a biological substance, usually made from pig
Pig
Pigs are a genus of even-toed ungulates within the family Suidae. The name hog most commonly refers to the domestic pig in everyday parlance, but technically encompasses several distinct species, including the wild boar...

 intestines. It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo
In vivo
In vivo refers to experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

(by injection), and also in vitro
In vitro
A procedure performed in vitro is performed not in a living organism but in a controlled environment, such as in a test tube or Petri dish...

to prevent blood or plasma clotting in or on medical devices. Vacutainer brand test tubes containing heparin are usually colored green.

Low molecular weight heparin


Low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....

 is a more highly processed product that is useful as it does not require monitoring of the APTT coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis , wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...

 parameter (it has more predictable plasma levels) and has fewer side effects.

Synthetic pentasaccharide inhibitors of factor Xa

  • Fondaparinux
    Fondaparinux
    Fondaparinux is an anticoagulant medication.It is marketed by GlaxoSmithKline.-Structure and mechanism:Fondaparinux is a synthetic pentasaccharide as evident by its chemical structure on the right...

     is a synthetic sugar composed of the five sugars (pentasaccharide) in heparin that bind to antithrombin. It is a smaller molecule than low molecular weight heparin.
  • Idraparinux
    Idraparinux
    Idraparinux sodium is an anticoagulant medication in development by Sanofi-Aventis.It has a similar chemical structure and the same method of action as fondaparinux, but with an elimination half-life about five to six times longer , which means that the drug should only need to be injected once a...


Major pharmaceutical Heparin recall due to contamination


In March 2008 major recalls of Heparin were announced by pharmaceuticals due to a suspected and unknown contamination of the raw Heparin stock imported from China . The U.S. Food and Drug Administration was quoted as stating that at least 19 deaths were believed linked to a raw Heparin ingredient imported from the People's Republic of China, and that they had also received 785 reports of serious injuries associated with the drug’s use. According to the New York Times: 'Problems with heparin reported to the agency include difficulty breathing, nausea, vomiting, excessive sweating and rapidly falling blood pressure that in some cases led to life-threatening shock'.

Direct thrombin inhibitors



Another type of anticoagulant is the direct thrombin inhibitor
Direct thrombin inhibitor
Direct thrombin inhibitors are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin. Some are in clinical use, while others are undergoing clinical development...

. Current members of this class include argatroban
Argatroban
Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food and Drug Administration for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia...

, lepirudin
Lepirudin
Lepirudin is an anticoagulant which functions as a direct thrombin inhibitor.It is derived from the saliva of the medicinal leech Hirudo medicinalis....

, bivalirudin
Bivalirudin
Bivalirudin is a drug that belongs to the anticoagulant class and acts as a direct thrombin inhibitor.-Basic chemical and pharmacological properties:...

, and dabigatran
Dabigatran
Dabigatran is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications, for some of which it may replace warfarin as the preferred anticoagulant. It is orally administered as the prodrug dabigatran etexilate...

. An oral direct thrombin inhibitor, ximelagatran
Ximelagatran
Ximelagatran is an anticoagulant that has been investigated extensively as a replacement for warfarin that would overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy...

 (Exanta) was denied approval by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...

 (FDA) in September 2004 http://www.fvleiden.org/ask/73.html and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks. http://www.astrazenecaclinicaltrials.com/article/512052.aspx

Anticoagulants outside the body


Laboratory
Medical laboratory
A medical laboratory or clinical laboratory is a laboratory where tests are done on clinical specimens in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease.-Departments:...

 instruments, test tubes, blood transfusion bags, and medical and surgical equipment will get clogged up and become nonoperational if blood is allowed to clot. Chemicals can be added to stop blood clotting. Apart from heparin, most of these chemicals work by binding
Chelation
Chelation is the formation or presence of two or more separate bindings between apolydentate ligand and a single central atom.Usually these ligands are organic compounds, and are called chelants, chelators, chelating agents, or sequestering agents....

 calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...

 ions, preventing the coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis , wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...

 proteins from using them.
  • EDTA
    EDTA
    EDTA is a widely used initialism for the chemical compound ethylenediaminetetraacetic acid . EDTA is a polyamino carboxylic acid with the formula [CH2N2]2. This colourless, water-soluble solid is widely used to dissolve scale...

     is denoted by mauve or purple caps on Vacutainer brand test tubes. This chemical strongly and irreversibly binds calcium. It is in a powdered form.
  • Citrate
    Citrate
    A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid...

     is usually in blue Vacutainer tube. It is in liquid form in the tube and is used for coagulation tests, as well as in blood transfusion bags. It gets rid of the calcium, but not as strongly as EDTA. Correct proportion of this anticoagulant to blood is crucial because of the dilution. It can be in the form of sodium citrate
    Sodium citrate
    Trisodium citrate has the chemical formula of Na3C6H5O7. It is sometimes referred to simply as sodium citrate, though sodium citrate can refer to any of the three sodium salts of citric acid. It possesses a saline, mildly tart, flavor. For this reason,...

     or ACD
    Acid-citrate-dextrose
    Acid Citrate Dextrose Solution is a solution of citric acid, sodium citrate and dextrose in water. It is mainly used as an anticoagulant to preserve blood, it is also used during procedures such as plasmapheresis instead of heparin...

    .
  • Oxalate
    Oxalate
    An oxalate is the deprotonated, charged form of oxalic acid or an ester of oxalic acid. The oxalate anion has the chemical formula C2O42−, also written...

     has a mechanism similar to that of citrate. It is the anticoagulant used in fluoride
    Fluoride
    Fluoride is the anion F, the reduced form of fluorine. Both organic and inorganic compounds containing the element fluorine are sometimes called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are distinct relative to other...

     (grey top) tubes.


For the meaning of more colors, see Vacutainer#including coagulants.

See also