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Structural formula
Excerpt from the structural formula of heparin
Representation of a section from the structure of heparin
Surname Heparin
other names

Glucuronic acid O- sulfate mucopolysaccharide

CAS number
  • 9005-49-6
  • 9045-22-1 (lithium salt)
  • 9041-08-1 ( sodium salt )
  • 60800-63-7 (ammonium salt)
  • 123228-39-7 (disaccharide)
Monomers / partial structures alternating between D- glucosamine and D- glucuronic acid or L- iduronic acid
PubChem 772
ATC code
DrugBank DB01109
Brief description

white to gray, amorphous and hygroscopic powder (heparin sodium)

Drug information
Drug class


Mechanism of action



Easily soluble in water and saline solution, practically insoluble in ethanol , acetone , benzene and diethyl ether (heparin sodium)

safety instructions
Please note the restricted labeling requirements for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Sodium salt

no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Heparins (in ancient Greek ἧπαρ hepar ' liver ') are the body's own polysaccharides , which have an inhibitory effect on the coagulation cascade and are therefore also used therapeutically for anticoagulation ( anticoagulation ). From a chemical point of view, these polyelectrolytes are glycosaminoglycans , consisting of a variable number of amino sugars with a molar mass between 4,000 and 40,000 (peak frequency around 15,000). Natural heparins are most efficiently extracted from pig small intestinal mucosa . The extraction from beef lungs has not been practiced since the BSE epidemic. Heparin is not absorbed through the gastrointestinal tract and must therefore be administered parenterally, i.e., depending on the area of ​​application, it must be injected or used as an ointment.

The anticoagulant effect is based on the fact that antithrombin III circulates in the blood , a protease inhibitor that inhibits activated coagulation factors such as thrombin and factor Xa . Heparin binds to antithrombin III, making the binding to the coagulation factors about a thousand times faster.

Heparin is used for the prophylaxis and therapy of thromboses . Its dose is not given in grams , but in International Units (IU): One unit prevents the coagulation of 1 ml of citrate-containing plasma after adding CaCl 2 at 37 ° C for one hour.

Heparin can also be used to prevent blood samples from clotting .

Heparin ointment is used to support the treatment of acute swelling conditions after blunt injuries ( bruises ), although heparin cannot penetrate the skin due to its physicochemical properties and is therefore ineffective in the form of an ointment.


Heparin was discovered by Jay McLean in 1916 and studied more closely by Howell and Charles Best in the 1920s . Heparin was then chemically deciphered in 1935. The first therapeutic application of heparin extracted from beef lung and pig intestine was in 1937 for the treatment of deep vein thrombosis by Clarence Crafoord in Stockholm. The market launch as a drug for the therapy and prophylaxis of thromboembolic diseases then took place in the 1940s.


Heparins are variably esterified glycosaminoglycans , each consisting of alternating sequences of D -glucosamine and a uronic acid ( D -glucuronic acid or L -iduronic acid ). Many monomer units contain sulfate groups attached to oxygen and nitrogen atoms.

From a chain length of five monosaccharides (three D- glucosamines and two uronic acids), heparins have an anticoagulant effect. Corresponding to the chain building blocks, they have many negative charges through which they also couple to antithrombin III. Heparins with chain lengths from 5 to 17 are referred to as low molecular weight heparins (LMWH) , English Low Molecular Weight Heparins (LMWH), with chain lengths from 18 as unfractionated heparins (UFH) .

The medicinally used, unfractionated heparin (also called standard heparin ) has a molar mass of 6000 to 30,000 Daltons (Da). By chemical or enzymatic cleavage and fractionation, low molecular weight, therapeutically usable heparins with average molar masses around 5000 Daltons are obtained: Certoparin (5400 Da ), Dalteparin (6100 Da), Enoxaparin (4500 Da), Parnaparin (5000 Da), Nadroparin (4300 Da) ), Reviparin (4400 Da) and Tinzaparin (6500 Da).


Heparin is not primarily formed in connective tissue , but almost only in mast cells and stored there.

Mechanism of action

Both LMWH and UFH bind antithrombins, especially antithrombin III (AT III). The resulting complex is called an immediate inhibitor and accelerates the inactivation of activated coagulation factors by a factor of a thousand. LMWH mainly inactivates the prothrombinase complex , consisting of activated factor X (Stuart Prower factor), activated factor V (pro-accelerin), calcium ions and phospholipids . In addition to the prothrombinase complex, UFH also inactivates activated factor II = thrombin . This explains the faster anticoagulant effect of UFH compared to LMWH.

Furthermore, the factors IX (anti- hemophilia factor B or Christmas factor ), XI (Rosenthal factor) and XII (Hagemann factor) are inactivated. The fibrinolytically active serine protease kallikrein is also activated. Another mechanism of action is that the polyanion heparin binds Ca ions; the reduction of Ca ions is anticoagulant.


Heparin is administered intravenously , subcutaneously, or percutaneously , the effectiveness of percutaneous administration being controversial. Subcutaneous administration of UFH results in a 30% bioavailability . When administered intravenously, there is initially a rapid elimination of 40% of the injected UFH (rapidly occurring saturation process due to the many negative charges UFH binds to the endothelium and macrophages as well as to plasma proteins) with a half-life of 5-15 minutes, which then slower in a Elimination ends with a half-life of 60–90 minutes ( renal elimination via glomerular filtration and tubular secretion). Only when all binding sites have been satisfied is the dose-effect relationship linear and the therapeutically effective level achieved. UFH does not cross the placenta and does not enter breast milk , so it can be used during pregnancy and breastfeeding .

LMWH have a lower affinity for plasma proteins , vascular matrix proteins , macrophages , platelets and endothelial cells . This explains better bioavailability , the longer elimination half-life and the exclusively renal clearance of LMWH. After subcutaneous injection there is a 90% + bioavailability. If the kidney function is impaired, the dose may have to be reduced. LMWH does not cross the placenta and it is not known to pass into breast milk.


Certoparin sodium (Mono-Embolex, 8000 IU), a low molecular weight heparin; 0.8 ml in a safety syringe

UFH is indicated among other things:

LMWH is indicated among other things:

Furthermore, heparin is used in the form of a so-called heparin block to hold open vascular catheters . The feed line is rinsed with heparinized NaCl solution so that no coagulation can take place in it.

Note: In Germany, many LMWH are not yet approved for any of these indications.


A critical risk-benefit analysis and careful laboratory monitoring of the patient are necessary. The term contraindication is to be seen relatively in this context:

high dose:

For regional anesthesia procedures close to the spinal cord ( spinal anesthesia or epidural anesthesia ), unfractionated heparin (UFH) should be discontinued four to six hours beforehand and given again at least one hour after the procedure. With LMWH prophylaxis, the active ingredient should be discontinued 12 hours beforehand, with LMWH therapy 24 hours beforehand and only given four hours after the procedure.

unwanted effects

The main side effect of heparin is bleeding. The risk is dose-dependent and increases with the simultaneous use of other drugs that inhibit blood clotting. Protamine can be administered intravenously as an antidote . As a side effect, heparin can cause heparin-induced thrombocytopenia . Antibodies against heparin can lead to life-threatening bleeding as well as blood clots. Treatment for longer than four weeks can cause a measurable decrease in bone density . Up to 2–3% of patients on long-term treatment with heparin experience osteoporotic vertebral body fractures. Reversible elevations in transaminases are also common. Low molecular weight heparins have a lower frequency of these side effects. However, compared to the longer-chain heparin, they have a lower therapeutic effect due to their lower effect on the deactivation of thrombin.


So that neither too much (risk of bleeding) nor too little (risk of thrombosis) heparin is given, the PTT (Partial Thromboplastin Time) should be determined in patients with UFH .

Low molecular weight heparin usually does not need to be controlled - an important benefit for the patient. If necessary, however, the correct dosage can be determined by measuring the anti-Xa activity. The measurement must be made four hours after the subcutaneous injection in order to create standardized conditions.

Finished medicinal products

Monopreparations (standard heparin)

Calciparine (CH), Gelparin (CH), Lioton (A, CH), Liquemin (CH), Lyman (CH), Sportino (D), Thrombareduct (D), Thrombophob (D), Vetren (D), numerous generics ( TOP, ROOF)

Monopreparations (low molecular weight heparins)

Mono-Embolex, Fragmin P, Clexane, Lovenox, Fraxiparin, Clivarin, Innohep

See also

Individual evidence

  1. Albert Gossauer: Structure and reactivity of biomolecules. Verlag Helvetica Chimica Acta, Zurich 2006, ISBN 3-906390-29-2 , p. 345.
  2. a b entry on heparin. In: Römpp Online . Georg Thieme Verlag, accessed on July 7, 2014.
  3. a b Data sheet Heparin sodium salt, Thermo Scientific at AlfaAesar, accessed on June 18, 2019 ( PDF )(JavaScript required) .
  4. a b Entry on heparin in the ChemIDplus database of the United States National Library of Medicine (NLM)
  5. a b c d e f g h Entry on heparin sodium in the ChemIDplus database of the United States National Library of Medicine (NLM)
  6. AOK.de : Therapies: Heparinization ( Memento from July 23, 2012 in the web archive archive.today ).
  7. Aktories, Förstermann, Hofmann, Starke: General and special pharmacology and toxicology. 9th edition. Urban & Fischer, p. 531.
  8. Instructions for use Heparin AL Gel 30,000 . ( Memento of March 21, 2014 in the Internet Archive ) (PDF; 43 kB) Aliud Pharma , April 2010.
  9. a b Heinz Lüllmann, Klaus Mohr: Pharmacology and Toxicology: Understanding the Effects of Medicines - Using Medicines Targeted. 16th edition. Georg Thieme Verlag, 2006, ISBN 3-13-368516-3 , p. 181.
  10. Ernst Kern : Seeing - Thinking - Acting of a surgeon in the 20th century. ecomed, Landsberg am Lech 2000, ISBN 3-609-20149-5 , p. 63.
  11. ^ Doris Schwarzmann-Schafhauser: Heparin. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 570.
  12. a b Wissenschaft-Online-Lexika: Entry on heparin in the Lexikon der Biochemie. Retrieved March 30, 2009.
  13. E. Mutschler, G. Geisslinger, HK Kroemer, S. Menzel, P. Ruth: Mutschler drug effects. Pharmacology - Clinical Pharmacology - Toxicology. 10th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2012, ISBN 978-3-8047-2898-1 , p. 478 f.
  14. Wiebke Gogarten, Hugo K. Van Aken: Perioperative thrombosis prophylaxis - platelet aggregation inhibitors - importance for anesthesia. In: AINS - Anesthesiology · Intensive Care Medicine · Emergency Medicine · Pain Therapy. Issue 04, April 2012, pp. 242-254, doi: 10.1055 / s-002-23167 .
  15. SA Kozek-Langenecker, D. Fries, M. Gütl, N. Hofmann, P. Innerhofer, W. Kneifl, L. Neuner, P. Perger, T. Pernerstorfer, G. Pfanner u. a .: Locoregional anesthesia with anticoagulant medication. Recommendations of the Perioperative Coagulation Working Group (AGPG) of the Austrian Society for Anaesthesiology and Intensive Care Medicine (ÖGARI). In: The Anaestesist. Volume 54, Number 5 2005, pp. 476-484, doi: 10.1007 / s00101-005-0827-0 .
  16. Jeffrey I. Weitz: Antiplatelet, Anticoagulant and Fibrinolytic Drugs. In: Anthony S. Fauci et al. a. (Ed.): Harrison's Principles of Internal Medicine. 18th edition. New York 2012, pp. 994-996.
  17. med4you.at: Anti-Xa activity (“heparin level”) - overview , February 6, 2009.