Description

Simple

A type of blood thinner used to prevent blood clots in a variety of medical conditions.

Clinical

An anticoagulant indicated for thromboprophylaxis and to treat thrombosis associated with a variety of conditions such as pulmonary embolism and atrial fibrillation.

Overview

Unfractionated heparin (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da. It is a naturally occurring anticoagulant released from mast cells. It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. UH is different from low molecular weight heparin (LMWH) in the following ways: the average molecular weight of LMWH is about 4.5 kDa whereas it is 15 kDa for UH; UH requires continuous infusions; activated partial prothrombin time (aPTT) monitoring is required when using UH; and UH has a higher risk of bleeding and higher risk of osteoporosis in long term use. Unfractionated heparin is more specific than LMWH for thrombin. Furthermore, the effects of UH can typically be reversed by using protamine sulfate.

Pharmacology

Indication

Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients... Read more

Pharmacodynamic

Unfractionated heparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3000 to 30,000 daltons. Heparin is obtained from liver, lung, mast cells, and other cells of vertebrates. Hepar... Read more

Mechanism of action

Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate... Read more

Absorption

Heparin must be given parenterally as it is not absorbed through the gastrointestinal mucosa. It is usually given by iv infusion or deep sc injection. The onset of action is immediate after iv injection but can be delayed 20 to 60 minutes following sc injection.

Plasma heparin concentrations may... Read more

Protein binding

Very high, mostly to low-density lipoproteins. It is also extensively bound by globulins and fibrinogens.

Volume of distribution

40-70 mL/min (approximately the same as blood volume)Although heparin does not distribute into adipose tissues, clinicians should use actual body weight in obese patients to account for extra vasculature.

Clearance

Adult Clearance = 0.43 ml/kg/min25-28 weeks gestation = 1.49 ml/kg/min

Half life

1.5 hours.

The plasma half-life of heparin increases from about 60 minutes with a 100 unit/kg dose to about 150 minutes with a 400 unit/kg dose.

Route of elimination

The drug appears to be removed mainly by the reticuloendothelial system. A small fraction of unchanged heparin also appears to be excreted in urine. Heparin cannot be eliminated by hemodialysis.

Toxicity

In mouse, the median lethal dose is greater than 5000 mg/kg. Another side effect is heparin-induced thrombocytopenia (HIT syndrome). Platelet counts usually do not fall until between days 5 and 12 of heparin therapy. HIT is caused by an immunological reaction that makes platelets form clots within t... Read more

Adverse Effects

Contraindications

  • Regions: US
  • Patient Conditions:
      • Name: Uncontrollable active bleeding state
      • Drugbank Id: DBCOND0108200
  • Regions: US
  • Patient Conditions:
      • Name: Inability to perform blood coagulation tests
      • Drugbank Id: DBCOND0108199
  • Hypersensitivity:
    • false
  • Regions: US
  • Regions: US
  • Patient Conditions:
      • Name: Severe Thrombocytopenia
      • Drugbank Id: DBCOND0043521
      • Modification Of:
        • Base:
          • Name: Thrombocytopenia
          • Drugbank Id: DBCOND0006608
        • Severity:
          • Includes:
            • severe

Food Interactions

  • Administer calcium supplement. This drug decreases calcium levels.
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include ginger, garlic, ginseng, green tea, and evening primrose.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(1,2,6,7-3H)Testosterone
(1,2,6,7-3H)Testosterone may increase the anticoagulant activities of Heparin.
(R)-warfarin
The risk or severity of bleeding can be increased when Heparin is combined with (R)-warfarin.
(S)-Warfarin
The risk or severity of bleeding can be increased when Heparin is combined with (S)-Warfarin.
1-Testosterone
1-Testosterone may increase the anticoagulant activities of Heparin.
18-methyl-19-nortestosterone
18-methyl-19-nortestosterone may increase the anticoagulant activities of Heparin.
3,5-Diiodotyrosine
3,5-Diiodotyrosine may increase the anticoagulant activities of Heparin.
4-hydroxycoumarin
The risk or severity of bleeding can be increased when Heparin is combined with 4-hydroxycoumarin.
4-Hydroxytestosterone
4-Hydroxytestosterone may increase the anticoagulant activities of Heparin.
5-fluorouridine
The therapeutic efficacy of Heparin can be decreased when used in combination with 5-fluorouridine.
5beta-dihydrotestosterone
5beta-dihydrotestosterone may increase the anticoagulant activities of Heparin.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of bleeding and hemorrhage can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Heparin.
Abciximab
The risk or severity of bleeding can be increased when Abciximab is combined with Heparin.
Acebutolol
The risk or severity of hyperkalemia can be increased when Heparin is combined with Acebutolol.
Aceclofenac
The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Heparin.
Acemetacin
The risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with Heparin.
Acenocoumarol
The risk or severity of bleeding can be increased when Heparin is combined with Acenocoumarol.
Acetylsalicylic acid
Acetylsalicylic acid may increase the anticoagulant activities of Heparin.
Agmatine
The risk or severity of hyperkalemia can be increased when Heparin is combined with Agmatine.
Alaproclate
The risk or severity of hemorrhage can be increased when Alaproclate is combined with Heparin.
Albutrepenonacog alfa
The therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Heparin.
10 References
  1. 1 . Linhardt RJ, Gunay NS: Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost. 1999;25 Suppl 3:5-16.PubMed: 10549711
  2. 2 . Ferro DR, Provasoli A, Ragazzi M, Casu B, Torri G, Bossennec V, Perly B, Sinay P, Petitou M, Choay J: Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences. Carbohydr Res. 1990 Jan 15;195(2):157-67.PubMed: 2331699
  3. 3 . Mulloy B, Forster MJ, Jones C, Davies DB: N.m.r. and molecular-modelling studies of the solution conformation of heparin. Biochem J. 1993 Aug 1;293 ( Pt 3):849-58.PubMed: 8352752
  4. 4 . Hirsh J, Raschke R: Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):188S-203S.PubMed: 15383472
  5. 5 . Petitou M, Herault JP, Bernat A, Driguez PA, Duchaussoy P, Lormeau JC, Herbert JM: Synthesis of thrombin-inhibiting heparin mimetics without side effects. Nature. 1999 Apr 1;398(6726):417-22.PubMed: 10201371
  6. 6 . Spruill WJ, Wade WE, Huckaby WG, Leslie RB: Achievement of anticoagulation by using a weight-based heparin dosing protocol for obese and nonobese patients. Am J Health Syst Pharm. 2001 Nov 15;58(22):2143-6.PubMed: 11760916
  7. 7 . McDonald MM, Jacobson LJ, Hay WW Jr, Hathaway WE: Heparin clearance in the newborn. Pediatr Res. 1981 Jul;15(7):1015-8.PubMed: 7254945
  8. 8 . Authors unspecified: Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983 Sep;72(3):356-8.PubMed: 6889041
  9. 9 . Authors unspecified: Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982 Aug;12(2):10-1.PubMed: 7188569
  10. 10 . Authors unspecified: Neonatal deaths associated with use of benzyl alcohol--United States. MMWR Morb Mortal Wkly Rep. 1982 Jun 11;31(22):290-1.PubMed: 6810084