anticoagulant

 

(ăn'tēkōăg'yələnt) , any of several substances that inhibit blood clot formation (see blood clotting). Some anticoagulants, such as the coumarin derivatives bishydroxycoumarin (Dicumarol) and warfarin (Coumadin) inhibit synthesis of prothrombin, a clot-forming substance, and other clotting factors. The coumarin derivatives compete with vitamin K, which is a necessary substance in prothrombin formation (see vitamin). They are only effective after the body's existing supply of prothrombin is depleted. Another anticoagulant, heparin, is a polysaccharide (see carbohydrate) found naturally in many cells. It acts in several ways: by preventing prothrombin formation; by preventing formation of fibrin, another clotting substance; and by decreasing the availability of a third clotting factor, thrombin. Heparin is obtained by extracting it from animal tissues. Anticoagulants are used to treat blood clots, which appear especially frequently in veins of the legs and pelvis in bedridden patients. Therapy helps to reduce the risk of clots reaching the lung, heart, or other organs. Heparin causes an instantaneous increase in blood-clotting time, and its effect lasts several hours.

An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some chemical compounds are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis equipment. They also have military applications, whereby their introduction into the wounds of enemy soldiers will make their treatment significantly more difficult.

As medications

Anticoagulants are given to people to stop thrombosis (blood clotting inappropriately in the blood vessels). This is useful in primary and secondary prevention of deep vein thrombosis, pulmonary embolism, myocardial infarctions and strokes in those who are predisposed.

Vitamin K antagonists

The oral anticoagulants are a class of pharmaceuticals that act by antagonizing the effects of vitamin K. Examples include warfarin. It is important to note that they take at least 48 to 72 hours for the anticoagulant effect to develop fully. In cases when any immediate effect is required, heparin must be given concomitantly. Generally, these anticoagulants are used to treat patients with deep-vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation (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.^[1]

These oral anticoagulants are used widely as poisons for mammalian pests, especially rodents. (For details, see rodenticide and warfarin.)

Available agents

The most important oral anticoagulants are:

• Warfarin (Coumadin). This is the main agent used in the U.S. and UK
• Acenocoumarol and phenprocoumon This is used more commonly outside the U.S. and the UK
• Phenindione

Heparin and derivative substances

Heparin is a biological substance, usually made from pig intestines. It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo (by injection), and also in vitro 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 is a more highly processed product that is useful as it does not require monitoring of the APTT coagulation parameter (it has more predictable plasma levels) and has fewer side effects.

Synthetic pentasaccharide inhibitors of factor Xa

• Fondaparinux 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

Direct thrombin inhibitors

Main article: direct thrombin inhibitor

Another type of anticoagulant is the direct thrombin inhibitor.^[2] Current members of this class include argatroban, lepirudin, and bivalirudin. An oral direct thrombin inhibitor, ximelagatran (Exanta®) was denied approval by the Food and Drug Administration (FDA) in September 2004 [1] and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks. [2]

Anticoagulants outside the body

Laboratory 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 calcium ions, preventing the coagulation proteins from using them.

• EDTA 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 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 or ACD.
• Oxalate has a similar mechanism to citrate. It is the anticoagulant used in fluoride (grey top) tubes.

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

References

1. ^ Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S (2007). "Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation". Circulation 115 (21): 2689-96. DOI:10.1161/CIRCULATIONAHA.106.653048. PMID 17515465. 
2. ^ Di Nisio M, Middeldorp S, Büller HR (2005). "Direct thrombin inhibitors". N. Engl. J. Med. 353 (10): 1028-40. DOI:10.1056/NEJMra044440. PMID 16148288. 

Interesting Links

• Software for Managing Anticoagulation Patients

See also

• Anticoagulation in pregnancy

Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)
Vitamin K antagonists	Acenocoumarol • Clorindione • Coumatetralyl • Dicumarol (Dicoumarol) • Diphenadione • Ethyl biscoumacetate • Phenprocoumon • Phenindione • Tioclomarol • Warfarin
Heparin group	Antithrombin III • Danaparoid • Heparin • Sulodexide • low molecular weight heparin (Bemiparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, Tinzaparin)
Glycoprotein IIb/IIIa inhibitors	Abciximab • Eptifibatide • Tirofiban
Other platelet aggregation inhibitors	Acetylsalicylic acid/Aspirin • Aloxiprin • Ditazole • Carbasalate calcium • Cloricromen • Clopidogrel • Dipyridamole • Indobufen • Picotamide • Prasugrel • Ticlopidine • Triflusal • prostaglandin analogue (Beraprost, Prostacyclin, Iloprost, Treprostinil)
Enzymes	plasminogen activators (Alteplase/Reteplase/Tenecteplase, Streptokinase, Urokinase/Saruplase, Anistreplase) • other serine endopeptidases (Ancrod, Drotrecogin alfa/Protein C, Fibrinolysin) • Brinase
Direct thrombin inhibitors	Argatroban • Bivalirudin • Dabigatran • Desirudin • Hirudin • Lepirudin • Melagatran • Ximelagatran
Other antithrombotics	Defibrotide • Dermatan sulfate • Fondaparinux • Rivaroxaban
Non-medicinal	Citrate • EDTA • Oxalate

Major Drug Groups
Gastrointestinal tract (A)	Antacids • Antiemetics  • H₂-receptor antagonists • Proton pump inhibitors • Laxatives • Antidiarrhoeals
Blood and blood forming organs (B)	Anticoagulants • Antiplatelets • Thrombolytics
Cardiovascular system (C)	Antiarrhythmics • Antihypertensives • Diuretics • Vasodilators • Antianginals • Beta blockers • Angiotensin converting enzyme inhibitors • Antihyperlipidemics
Skin (D)	Antipruritics
Reproductive system (G)	Hormonal contraception • Fertility agents • Selective estrogen receptor modulators • Sex hormones
Endocrine system (H)	Anti-diabetics • Corticosteroids • Sex hormones • Thyroid hormones
Infections and Infestations (J, P)	Antibiotics • Antivirals • Vaccines • Antifungals • Antiprotozoals • Anthelmintics
Malignant and Immune disease (L)	Anticancer agents • Immunosuppressants
Muscles, Bones, and Joints (M)	Anabolic steroids • Anti-inflammatories • Antirheumatics • Corticosteroids • Muscle relaxants
Brain and Nervous system (N)	Anesthetics • Analgesics • Anticonvulsants • Mood stabilizers  • Anxiolytics • Antipsychotics • Antidepressants • Nervous system stimulants
Respiratory system (R)	Bronchodilators • Decongestants  • Antihistamines

Donate to Wikimedia