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Anticoagulant

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Antithrombotic agents
Drug class
Class identifiers
ATC codeB01
Clinical data
Drugs.comDrug Classes
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MeSHD005343
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In Wikidata

Anticoagulants (antithrombics, fibrinolytic, and thrombolytics) are a class of drugs that work to prevent the coagulation (clotting) of blood. Such substances occur naturally in leeches and blood-sucking insects. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis equipment.

As medications

Anticoagulants reduce blood clotting. This prevents deep vein thrombosis, pulmonary embolism, myocardial infarction and ischemic stroke.

Coumarins (vitamin K antagonists)

Further information: Vitamin K antagonist

These oral anticoagulants are derived from coumarin, which is found in many plants. A prominent member of this class is warfarin (Coumadin). It takes at least 48 to 72 hours for the anticoagulant effect to develop. Where an immediate effect is required, heparin must be given concomitantly. These anticoagulants are used to treat patients with deep-vein thrombosis (DVT), pulmonary embolism (PE) and to prevent emboli in patients with 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.) Depletion of vitamin K by Coumadin therapy increases risk of arterial calcification and heart valve calcification, especially if too much vitamin D is present.[2]

Available agents

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. In venipuncture, Vacutainer brand blood collecting tubes containing heparin usually have a green cap.

Major pharmaceutical heparin recall due to contamination

In March 2008, major recalls of heparin were announced by pharmaceutical companies due to a suspected and unknown contamination of the raw heparin stock imported from China.[4][5] The contaminant was later found to be a compound called oversulfated chondroitin sulfate.[6] The US Food and Drug Administration was quoted as stating at least 19 deaths were believed linked to a raw heparin ingredient imported from the People's Republic of China, and 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, a more highly processed product, 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 factor Xa inhibitors

Main article: Direct Xa inhibitor

Drugs such as rivaroxaban and apixaban work by inhibiting factor Xa directly (unlike the heparins and fondaparinux, which work via antithrombin activation).

Direct thrombin inhibitors

Main article: direct thrombin inhibitor

Another type of anticoagulant is the direct thrombin inhibitor.[7] Current members of this class include the bivalent drugs hirudin, lepirudin, and bivalirudin; and the monovalent drugs argatroban and dabigatran. 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] In November 2010, dabigatran was approved by the FDA to treat atrial fibrillation.

Antithrombin protein therapeutics

The antithrombin protein itself is used as a protein therapeutic that can be purified from human plasma[8] or produced recombinantly (for example, Atryn, which is produced in the milk of genetically modified goats.[9][10])

Antithrombin is approved by the FDA as an anticoagulant for the prevention of clots before, during, or after surgery or birthing in patients with hereditary antithrombin deficiency.[8][10]

Other types of anticoagulants

Many other anticoagulants exist, for use in research and development, diagnostics, or as drug candidates.

Food and herbal supplements

Foods and food supplements with blood-thinning effects include nattokinase, lumbrokinase, beer, bilberry, celery, cranberries, fish oil, garlic, ginger, ginkgo, ginseng, green tea, horse chestnut, licorice, niacin, onion, papaya, pomegranate, red clover, soybean, St. John’s wort, turmeric, wheatgrass, and willow bark.[11] Many herbal supplements have blood-thinning properties, such as danshen and feverfew. Multivitamins that do not interact with clotting are available for patients on anticoagulants.

However, some foods and supplements encourage clotting and should be avoided when using anticoagulants. These include alfalfa, avocado, cat's claw, coenzyme Q10, and dark leafy greens such as spinach.

Grapefruit interferes with some anticoagulant drugs, increasing the amount of time it takes for them to be metabolized out of the body, and so should be eaten only with caution when on anticoagulant drugs.

General indications

Therapeutic uses of anticoagulants include atrial fibrillation, pulmonary embolism, deep vein thrombosis, venous thromboembolism, congestive heart failure, stroke, myocardial infarction, and genetic or acquired hypercoagulability.

Laboratory use

Laboratory instruments, blood transfusion bags, and medical and surgical equipment will get clogged up and become nonoperational if blood is allowed to clot. In addition, test tubes used for laboratory blood tests will have chemicals 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 strongly and irreversibly binds calcium. It is in a powdered form. Full Form of EDTA is Ethyinene Diamine Tetra Acitic Acid. It chelates calcium ion to prevent blood from clotting.
  • Citrate is in liquid form in the tube and is used for coagulation tests, as well as in blood transfusion bags. It binds the calcium, but not as strongly as EDTA. Correct proportion of this anticoagulant to blood is crucial because of the dilution, and it can be reversed with the addition of calcium. It can be in the form of sodium citrate or acid-citrate-dextrose.
  • Oxalate has a mechanism similar to that of citrate. It is the anticoagulant used in fluoride oxalate tubes used to determine glucose and lactate levels.

See also

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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Adams J, Pepping J (1 Aug 2005). "Vitamin K in the treatment and prevention of osteoporosis and arterial calcification" (PDF). American Journal of Health-System Pharmacy. 62 (15): 1574–81. doi:10.2146/ajhp040357. PMID 16030366. Retrieved 2012-10-03.
  3. ^ Ron Winslow; Avery Johnson (2007-12-10). "Race Is on for the Next Blood Thinner". Wall Street Journal. p. A12. Retrieved 2008-01-06. ...in a market now dominated by one of the oldest mainstay pills in medicine: the blood thinner warfarin. At least five next-generation blood thinners are in advanced testing to treat or prevent potentially debilitating or life-threatening blood clots in surgery and heart patients. First candidates could reach the market in 2009.
  4. ^ New York Times, March 6, 2008 Drug Tied to China Had Contaminant, F.D.A. Says, retrieved 2008-03-07
  5. ^ New York Times, March 7, 2008 German Authorities Report Problems With Blood Thinner, retrieved 2008-03-07
  6. ^ Blossom, DB; Kallen, AJ; Patel, PR; Elward, A; Robinson, L; Gao, G; Langer, R; Perkins, KM; Jaeger, JL (2008). "Outbreak of adverse reactions associated with contaminated heparin". N Engl J Med. 359 (25): 2674–84. doi:10.1056/NEJMoa0806450. PMID 19052120. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  7. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ a b Thrombate III label
  9. ^ FDA website for ATryn (BL 125284)
  10. ^ a b Antithrombin (Recombinant) US Package Insert ATryn for Injection February 3, 2009
  11. ^ Wittkowsky AK (September 2001). "Drug interactions update: drugs, herbs, and oral anticoagulation". J. Thromb. Thrombolysis. 12 (1): 67–71. doi:10.1023/A:1012742628628. PMID 11711691.
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