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Online  Anticoagulation Information for Pharmacists and Patients

Anticoagulants from Wikipedia (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.

  • 1 Medications
    • 1.1 Coumarins (vitamin K antagonists)
      • 1.1.1 Adverse effects
      • 1.1.2 Available agents
    • 1.2 Heparin and derivative substances
      • 1.2.1 Major pharmaceutical heparin recall due to contamination
      • 1.2.2 Low molecular weight heparin
      • 1.2.3 Synthetic pentasaccharide inhibitors of factor Xa
    • 1.3 Direct factor Xa inhibitors
    • 1.4 Direct thrombin inhibitors
    • 1.5 Antithrombin protein therapeutics
    • 1.6 Other types of anticoagulants
  • 2 Food and herbal supplements
  • 3 General indications
  • 4 Laboratory use
  • 5 See also
  • 6 References
  • 7 External links

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.  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. 

Available agents

  • Warfarin (Coumadin) is the main agent used in the US and UK.
  • Acenocoumarol and phenprocoumon are used more commonly outside the US and the UK.
  • Atromentin
  • Brodifacoum is used as rat poison, but is 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. In venipuncture, Vacutainer brand blood collecting tubes containing heparin usually have a green cap.

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, apixaban and edoxaban work by inhibiting factor Xa directly (unlike the heparins and fondaparinux, which work via antithrombin activation). Also betrixaban (LY517717) from Portola Pharmaceuticals, darexaban (YM150) from Astellas and more recent TAK-442 letaxaban (Takeda) and eribaxaban (PD0348292) (Pfizer). The development of darexaban was discontinued in September 2011: in a trial for prevention of recurrences of myocardial infarction in top of dual antiplatelet therapy, the drug didn't work and the risk for bleeding was increased bij 300%. The development of letaxaban was discontinued for acute coronary syndrome in May 2011 following negative results from a Phase II study.

Heparin-induced thrombocytopenia (HIT)

Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis, the abnormal formation of blood clots inside a blood vessel, and when thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies that activate platelets. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood tests.

The treatment of HIT requires both protection from thrombosis and choice of an agent that will not reduce the platelet count further. Several agents exist for this purpose, mainly lepirudin and argatroban. While heparin was discovered in the 1930s, HIT was not reported until the 1960s and 1970s. 

Treatment

Molecular structure of argatroban, a direct thrombin inhibitor used as an alternative to heparin in HIT. Given the fact that HIT predisposes strongly to new episodes of thrombosis, it is not sufficient to simply discontinue the heparin administration. Generally, an alternative anticoagulant is needed to suppress the thrombotic tendency while the generation of antibodies stops and the platelet count recovers. To make matters more complicated, the other most commonly used anticoagulant, warfarin, should not be used in HIT until the platelet count is at least 150 x 10^9/L because there is a very high risk of warfarin necrosis in people with HIT who have low platelet counts. Warfarin necrosis is the development of skin gangrene in those receiving warfarin or a similar vitamin K inhibitor. If the patient was receiving warfarin at the time when HIT is diagnosed, the activity of warfarin is reversed with vitamin K. Transfusing platelets is discouraged, as there is a theoretical risk that this may worsen the risk of thrombosis; the platelet count is rarely low enough to be the principal cause of significant hemorrhage.

Three agents are used to provide anticoagulation in patients with strongly suspected or proven HIT: danaparoid, lepirudin, and argatroban. These are alternatives to heparin therapy. Not all agents are registered in all countries. For instance, argatroban is not used in the United Kingdom and danaparoid is not available in the United States. Lepirudin production stopped on May 31, 2012. A fourth agent acting as a Factor Xa inhibitor also has an off label use for HIT treatment known as fondaparinux and is available and commonly used in the United States.

According to systematic review, patients treated with lepirudin for HIT showed a relative risk reduction of clinical outcome (death, amputation, etc.) to be 0.52 and 0.42 when compared to patient controls. In addition, patients treated with argatroban for HIT showed a relative risk reduction of the above clinical outcomes to be 0.20 and 0.18.


Direct thrombin inhibitors

Main article: direct thrombin inhibitor

Another type of anticoagulant is the direct thrombin inhibitor. 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   and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks.  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 or produced recombinantly (for example, Atryn, which is produced in the milk of genetically modified goats.)

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.

Other types of anticoagulants

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

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

Anticoagulation Related Websiles

AF Answers: What is Atrial Fibrillation

Agency for Healthcare Research and Quality: Blood Thinner Pills

American Stroke Association

Anticoagulant and Antiplatelet Drugs

Antithrombotic Therapy and Prevention of Thrombosis

Anticoagulant Treatment‎

Anticoagulation - American Heart Association

Anticoagulation Articles

Anticoagulation Resource Center

Anticoagulation Therapy - Anticoagulation Europe

ClotCare  Online Resource

Coumadin (warfarin sodium tablet, USP) Crystalline

EHRA Practical Guide on the use of new oral anticoagulants

Guide to Anticoagulant Therapy: Heparin 

Guidelines For Antithrombotic Therapy

LOVENOX® (enoxaparin sodium injection) Dosing for DVT

Lovenox® (enoxaparin sodium injection) Product Information

Lovenox (Enoxaparin Sodium Injection) Drug Information 
 
MedicineNet.com: Warfarin (Coumadin)

New Oral Anticoagulants for Atrial Fibrillation

New oral anticoagulants: which one should my patient use?

Outpatient Management of Anticoagulation Therapy - American What is Pradaxa

Pharmacology –What’s New in Anticoagulation Medications

Pradaxa Information

Review: New Oral Anticoagulants for Afib, VTE, and ACS -

The Coalition to Prevent Deep-Vein Thrombosis (DVT)

XARELTO® (rivaroxaban)

XARELTO®

Warfarin and Beyond: An Update On Oral Anticoagulation Therapy

Adult Anticoagulation Orders Following Placement of Impella®

IMPELLA 2.5 ADDENDUM TO ADULT CRITICAL CARE ... - InfoClique

Use of the Impella 2.5 in High-Risk Percutaneous Coronary

Unfractionated Heparin Infusion Protocol - University Health System

Principles of Impella Cardiac Support - Cardiac Interventions Today

The Duration of Impella 2.5 Circulatory Support and Length of



Anticoagulation Protocols

Heparin & Enoxaparin - VUNeo.Org

Transition of Anticoagulants 2014 - Thomas Land Publishers

(BESt). Management of low molecular weight heparin therapy

University of Connecticut Health Center- John ... - Pharmacy

Anticoagulation Therapy Guidelines for Medical Indications

Guidelines For Antithrombotic Therapy

Guidelines for Deep Venous Thrombosis (DVT) Prophylaxis

Anticoagulation Bridging - Intermountain Physician

Pharmacokinetics of the low molecular weight heparin


Heparin Induced Thrombocytopenia Related Links

American Association of Blood Banks
 

American Red Cross 

BleedingWeb.com 

Bloodline 

Blood management abstracts (SABM).

California Blood Bank Society 

Factor VIIa

Haemophilia Forum

Heparin Induced Thrombocytopenia

International Society on Thrombosis and Haemostasis.

Irontherapy.org

Lipids Online 

Management of anticoagulation, an anticoagulation management service.

DocMD's SpecialtyLinks 

DocMD's Medline access page.

National Heart Lung and Blood Institute at the NIH

Network for Advancement of Transfusion Alternatives.

National Organization for Rare Disorders.

National Hemophilia Foundation's web site

Platelet inhibitors 

Novoseven 

Plasma Protein Therapeutics Association (PPTA)

Regional anesthesia guidelines

Resource guide 

Scientific slides 

Spanish language information and sites on hemostasis.

Society for the Advancement of Blood Management 

CABG-consult.com.

Hemostasiscme.org.

Transfusion Medicine and Alternatives in Transfusion Medicine 

Trigger 

VascularWeb 

Web based 
illustrations about hemostasis from diaPharma site.

Heparin Induced Thrombocytopenia.

Heparin Induced Thrombocytopenia (HIT)  


Hit  Related Links

American Red Cross

Frequently asked questions about HIT 

HIT and cardiopulmonary bypass 

HIT guidelines

HIT information 

Incidence of HIT

Heparin Induced Thrombocytopenia

DocMD's Medline access page.

Overview of HIT 

Pediatric patients and HIT 

Temporal aspects of HIT

von Willebrand Disease


Protocol

Hemostatic Drug Information Links

Abciximab (ReoPro) - click  ReoPro

Adverse drug reactions - Click Adversereactions.com

Aprotinin (trasylol) - Click trasylol

Argatroban - Click argatroban.com

For.hemophilia.immunedisorders.shock- Click  www.alphather.com

Bivalurdin (Angiomax)-Click www.angiomax.com

Clopidogrel (Plavix)-Click www.plavix.com

Danaproid (Orgaran)-Click www.orgaran.com

Enoxaparin (Lovenox)-Click www.lovenox.com

Epoetin alfa (Procrit)-Click www.procrit.com

Recombinant factor VIIa (Novoseven)-Click Factorviia.com

Lepirudin, recombinant hirudin (Refludan)-Click www.refludan.com

Platelet inhibitors-Click PlateletInhibitors.com

Protamine-Click Protamine 

Tirofiban (Aggrastat)-Click www.aggrastat.com

warfarin (Coumadin)-Click www.coumadin.com.