Anticoagulant
Overview
 
An anticoagulant is a substance that prevents coagulation (clotting) of blood. 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 to prevent blood loss...

 disorders. Some anticoagulants 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 receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

 bags, and renal dialysis equipment.
Anticoagulants reduce blood clotting. This prevents deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...

, 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, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 and stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , 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 blockage , or a hemorrhage...

.
These oral anticoagulants are a class of pharmaceuticals
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 that antagonize the effects of vitamin K1
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...

.
Encyclopedia
An anticoagulant is a substance that prevents coagulation (clotting) of blood. 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 to prevent blood loss...

 disorders. Some anticoagulants 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 receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

 bags, and renal dialysis equipment.

As medications

Anticoagulants reduce blood clotting. This prevents deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...

, 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, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 and stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , 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 blockage , or a hemorrhage...

.

Coumadins (Vitamin K antagonists)

These oral anticoagulants are a class of pharmaceuticals
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 that antagonize the effects of vitamin K1
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...

. Examples include warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

. It takes at least 48 to 72 hours for the anticoagulant effect to develop. Where an immediate effect is required, heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...

 must be given concomitantly. 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 . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving 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 is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

.)

Depletion of vitamin K by coumadin 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 is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

     (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.- Dosage :...

     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...

     This is used more commonly outside the U.S. and the UK
  • Brodifacoum
    Brodifacoum
    Brodifacoum is a highly lethal vitamin K antagonist anticoagulant poison. In recent years, it has become one of the world's most widely used pesticides...

     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 , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...

 is a biological substance, usually made from pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...

 intestines. It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo
In vivo
In vivo is 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
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

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

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 contaminant was later found to be a non-naturally occurring compound called oversulfated chondroitin sulfate. 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'.

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, the cessation of blood loss from a damaged vessel, 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 chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline.-Structure and mechanism:Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor...

     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...



Direct Factor Xa inhibitors

Drugs such as rivaroxaban
Rivaroxaban
Rivaroxaban is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. In the United States, it is marketed by Janssen Pharmaceutica. It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is well absorbed from the gut...

 and apixaban
Apixaban
Apixaban is a compound being investigated as an anticoagulant. It is a direct factor Xa inhibitor. It is presently undergoing phase III trials in the prevention of venous thromboembolism, together with a number of related competing compounds, such as rivaroxaban...

 work by inhibiting Factor Xa directly (unlike the heparins and fondaparinux, which work via antithrombin activation).

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 the bivalent drugs hirudin
Hirudin
Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches that has a blood anticoagulant property...

, lepirudin
Lepirudin
Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor.Brand name: Refludan, Generic: Lepirudin rDNA for injection.Lepirudin is a recombinant hirudin derived from yeast cells. It is almost identical to...

, and bivalirudin
Bivalirudin
Bivalirudin is a specific and reversible direct thrombin inhibitor .1Chemically, it is a synthetic congener of the naturally occurring drug hirudin .Bivalirudin is a DTI that overcomes many limitations seen with indirect thrombin inhibitors, such as heparin...

; and the monovalent drugs 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...

 and dabigatran
Dabigatran
Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors...

. 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 an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 (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 In November 2010 Dabigatran was approved by the FDA to treat Atrial Fibrillation.

Other types of anticoagulants

Many other anticoagulants exist, for use in Research & Development
Research and development
The phrase research and development , according to the Organization for Economic Co-operation and Development, refers to "creative work undertaken on a systematic basis in order to increase the stock of knowledge, including knowledge of man, culture and society, and the use of this stock of...

, and more or less uses as drug candidates or diagnostics
  • Batroxobin
    Batroxobin
    Batroxobin is a serine protease derived from the venom of Bothrops atrox. Its molecular weight is approximately 43,000 g/mol−1.This thrombin-like proteolytic enzyme splits the 16 Arg-17 Gly bond in the A-chain of fibrinogen, releasing fibrinopeptide A and leading to the clot formation through...

    , a toxin
    Toxin
    A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

     from a snake
    Snake
    Snakes are elongate, legless, carnivorous reptiles of the suborder Serpentes that can be distinguished from legless lizards by their lack of eyelids and external ears. Like all squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales...

     venom
    Venom
    Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...

     that clots platelet-rich plasma without affecting platelet
    Platelet
    Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days...

    s functions (lyses fibrinogen
    Fibrinogen
    Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...

    ).
  • Hementin
    Hementin
    Hementin is an anticoagulant protease from the salivary glands of the giant Amazon leech . Hementin dissolves a type of platelet rich blood clot which cannot be dissolved by other well used drugs like streptokinase and urokinase....

    is an anticoagulant protease from the salivary glands of Haementeria ghilianii
    Haementeria ghilianii
    Haementeria ghilianii, also known as the Giant Amazon Leech, is one the world's largest species of leech. It can grow to be 450 millimetres in length and 100 millimetres in width...


Food supplements

Food supplements with blood thinning effect include Nattokinase
Nattokinase
Nattokinase is an enzyme extracted and purified from a Japanese food called nattō. Nattō is a food made from fermented soybeans that has been eaten in Japan for many years. Nattō is produced by fermentation by adding the bacterium Bacillus natto, a beneficial bacteria, to boiled soybeans. The...

 and Lumbrokinase
Lumbrokinase
Lumbrokinase is a fibrinolytic enzyme present in the earthworm Lumbricus bimastus. It has been investigated as an experimental antithrombotic agent....


General indications

Therapeutic uses of anticoagulants include atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...

, 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), deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...

 (DVT), or venous thromboembolism (VTE), congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , 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 blockage , or a hemorrhage...

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

, genetic or acquired hypercoagulability

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 coordinate bonds between apolydentate ligand and a single central atom....

 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 gray 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, the cessation of blood loss from a damaged vessel, 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
    Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...

     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. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...

     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
    Monosodium citrate
    Monosodium citrate, or sodium dihydrogen citrate, is an acid salt with the chemical formula NaH2C6H5O7, or C3H4OH2COONa. Since it has two remaining open spots on the citrate anion, it is used as a relatively strong sequestrant. It is used to prevent platelet clumping in blood samples...

     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 specimens required for tissue typing, it is also used during procedures such as plasmapheresis instead of heparin...

    .
  • Oxalate
    Oxalate
    Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either...

     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 when as an ion and when bonded to another element. Both organofluorine compounds and inorganic fluorine containing compounds are called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are...

     (grey top) tubes.


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

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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