Anticoagulant

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 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 stroke.

Coumadins (Vitamin K antagonists)

Further information: Vitamin K antagonist

These oral anticoagulants are a class of pharmaceuticals that antagonize the effects of vitamin K₁. Examples include warfarin. 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), 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

• Warfarin (Coumadin) This is the main agent used in the U.S. and UK^[3]
• Acenocoumarol and phenprocoumon This is used more commonly outside the U.S. and the UK
• Brodifacoum Rat poison, not used medically
• 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.

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.^[4][5] The contaminant was later found to be a non-naturally occurring compound called oversulfated chondroitin sulfate.^[6] 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 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 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.

Other types of anticoagulants

Many other anticoagulants exist, for use in Research & Development, and more or less uses as drug candidates or diagnostics

• Batroxobin, a toxin from a snake venom that clots platelet-rich plasma without affecting platelets functions (lyses fibrinogen).
• Hementin is an anticoagulant protease from the salivary glands of Haementeria ghilianii

Food supplements

Food supplements with blood thinning effect include Nattokinase and Lumbrokinase

General indications

Therapeutic uses of anticoagulants include atrial fibrillation, pulmonary embolism (PE), deep vein thrombosis (DVT), or venous thromboembolism (VTE), congestive heart failure, stroke, myocardial infarction, genetic or acquired hypercoagulability

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 mechanism similar to that of citrate. It is the anticoagulant used in fluoride (grey top) tubes.

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

See also

• Anticoagulation in pregnancy
• Nitrophorin

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. ^ Adams J, Pepping J. "Vitamin K in the treatment and prevention of osteoporosis and arterial calcification", Am J Health Sys Pharm, Aug 1, 2005, vol. 62, no. 15, pp. 1574-81.
3. ^ Ron Winslow; Avery Johnson (2007-12-10). "Race Is on for the Next Blood Thinner". Wall Street Journal: p. A12. http://online.wsj.com/article/SB119725064671318856.html. 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 et al. Outbreak of adverse reactions associated with contaminated heparin. N Engl J Med. 2008 Dec 18;359(25):2674-84.
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. 

External links

• AgroMedic - Medicinal Leeches,Malaysia Leeches(Hirudinaria Manillensis)
• Staying Active and Healthy with Blood Thinners DVD by the Agency for Healthcare Research and Quality