Danaparoid is a heparinoid with anticoagulant and antithrombotic activities used for the treatment of acute episode of Heparin-Induced Thrombocytopenia (HIT), and for prophylaxis in patients with a history of HIT.

Brand Names
Generic Name
DrugBank Accession Number

Danaparoid is a low-molecular-weight heparinoid with an average molecular weight of 5500 Daltons consisting of a mixture of glycosaminoglycans 2. The active constituents are heparan, dermatan and Chondroitin sulfate 5, and they are isolated from the porcine intestinal mucosa Label. Danaparoid possesses a potent antithrombic activity that works by inhibiting activated factor X (Factor Xa) and activated factor II (Factor IIa). It is chemically distinct from heparin by containing different protein binding properties, thus has lower cross-reactivity in heparin-intolerant patients. Danaproid is used in the treatment of heparin-induced thrombocytopenia (HIT) as an off-label indication and prevention of post-operative deep venous thrombosis (DVT). While it was initially approved by the FDA as Orgaran™, danaparoid was withdrawn by Organon International on August 14, 2002, due to a shortage in drug substance by the manufacturer. The use of Orgaran™ was discontinued in the United States however it is available in several other countries including European countries and Japan. Danaparoid sodium is the common salt form in therapeutic preparations and is typically administered subcutaneously.

Small Molecule
Approved, Withdrawn
Not Available



Indicated for the prophylaxis of post-operative deep venous thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients undergoing elective hip replacement surgery Label.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prophylaxis ofDeep vein thrombosis caused by major abdominal surgery••••••••••••
Prophylaxis ofDeep vein thrombosis caused by orthopedic surgery••••••••••••
Prophylaxis ofDeep vein thrombosis caused by thoracic surgery••••••••••••
Management ofHeparin-induced thrombocytopenia••••••••••••
Management ofNon-hemorrhagic stroke••••••••••••
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Danaparoid contains a mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate in amounts of approximately 84%, 12% and 4%, respectively 3. Danaparoid is as an antithrombotic agent that prevents the formation of fibrin in the coagulation pathway. It has a high antifactor Xa to antifactor IIa (thrombin) activity that primarily works via antithrombin III-mediated inhibition of factor Xa 3. The ratio of antifactor Xa to antifactor II activity is ≥ 20:1 3. Danaparoid has a minor effect on platelet function and aggregation Label. In a worldwide compassionate-use programme involving a total of 667 patients with heparin-induced thrombocytopenia (HIT), treatment with danaparoid resulted in 93% of successful outcomes in resolving HIT 3.

In healthy volunteers, danaparoid caused significantly less prolongation o f the activated partial thromboplastin time (APTT) and was associated with a significantly lower thrombin time than unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) 3. Danaparoid displays lower lipolytic activity than UFH in vitro and in healthy individuals, leading to lower plasma levels of free fatty acids 3. Danaparoid has been associated with the cross-reactivity with pathogenic heparin-induced platelet-factor 4 (PF4) antibodies, which occurs in about 10 % or more by in vitro testing 1. The clinical relevance of this effect is not fully understood 1.

Mechanism of action

In the coagulation cascade leading to clot formation, factor X and factor II requires activation to promote subsequent conversion of fibrinogen to fibrin. The mechanism of action of danaparoid resulting in anticoagulant and antithrombic effects involves a complex interaction between 2 components, factor IIa and in particular, factor Xa 3. Via binding to antithrombin and inducing a conformational change 4, danaparoid enhances and catalyzes the the binding of factor Xa to antithrombin, which induces antithrombin-mediated inactivation of factor Xa. This leads to inhibition of thrombin generation and subsequently, thrombus formation 2. Danaparoid also weakly enhances antithrombin III and heparin cofactor II inactivation of factor IIa 2. There is evidence that danaparoid also suppresses the activation of factor IX which, in conjunction with simultaneous inhibition of factor X, may lead to antithrombic effects 3.

positive allosteric modulator

Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly antifactor Xa and antifactor IIa activities. The bioavailability of danaparoid is 100% following subcutaneous administration Label. Following administration of single subcutaneous doses of 750, 1500, 2250, and 3250 anti-Xa units of danaparoid, the peak plasma anti-Xa activities were 102.4, 206.1, 283.9, and 403.4 mU/mL, respectively Label. The time to reach maximum anti-Xa activity is approximately 2-5 hours Label.

Volume of distribution

Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. The volumes of distribution of anti-Xa and anti-IIa activities are 9.1 L and 7.3-9.0 L, respectively 3.

Protein binding

Not Available


There is no evidence of hepatic metabolism and danaparoid is unlikely to undergo cellular metabolism 3.

Route of elimination

Renal excretion is the main route of elimination, accounting for approximately 40-50% of the total clearance of antifactor Xa activity following intravenous administration of danaparoid 3. Therefore in patients with severe renal impairment, the elimination half-life of anti-Xa activity may be prolonged Label.


Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. The elimination half-life ranges from 19.2 to 24.5 hours during anti-Xa activity and ranges from 1.8 to 4.3 hours during anti-IIa activity 3.


Pharmacokinetic studies on danaparoid are based on the kinetics of its anticoagulant activities, which are mostly anti factor Xa and anti factor IIa activities. Total plasma clearance is about 0.36 L/h during anti-Xa activity, which may be accelerated with higher body surface area Label. Total plasma clearance during anti-IIa activity ranges from 2.3 to 3 L 3.

Adverse Effects
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Subcutaneous administration of a single dose at 3800 anti-Xa units/kg, which is 20.5 times the recommended dose for humans based on body surface area, was found to be lethal to female rats. Lethal effects were seen in male rats when administering a single subcutaneous dose at 15200 anti-Xa units/kg, which is approximately 82 times the recommended human dose based on body surface area Label. In rats, the symptoms of acute toxicity following intravenous administration included respiratory depression, prostration and twitching Label.

Accidental overdosage of danaparoid may lead to severe bleeding complications. While protamine sulfate may partially neutralize the anti-Xa actions of danaparoid, there is no evidence that it is capable of reducing severe non-surgical bleeding during treatment of danaparoid. In case of serious bleeding, danaparoid should be discontinued and blood transfusions should be administered if necessary. Withdrawal of danaparoid is expected to restore the coagulation balance without rebound phenomenon Label.

There is no evidence of danaparoid to have a potential to induce carcinogenesis, mutagenesis and impairment of fertility Label.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Danaparoid.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Danaparoid.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Danaparoid.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Danaparoid is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Danaparoid.
Food Interactions
  • Avoid excessive or chronic alcohol consumption. Ingesting alcohol increases the risk of bleeding.
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. These may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.


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Product Ingredients
IngredientUNIICASInChI Key
Danaparoid sodium5004UU3156Not AvailableNot applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OrgaranSolution750 unit / 0.6 mLIntravenous; SubcutaneousAspen Pharmacare Canada Inc.1995-12-31Not applicableCanada flag


ATC Codes
B01AB09 — Danaparoid
Drug Categories
Not classified
Affected organisms
Not Available

Chemical Identifiers

CAS number
InChI Key
Not Available
Not Available
Not Available
Not Available


General References
  1. Kodityal S, Manhas AH, Udden M, Rice L: Danaparoid for heparin-induced thrombocytopenia: an analysis of treatment failures. Eur J Haematol. 2003 Aug;71(2):109-13. [Article]
  2. Ibbotson T, Perry CM: Danaparoid: a review of its use in thromboembolic and coagulation disorders. Drugs. 2002;62(15):2283-314. [Article]
  3. Wilde MI, Markham A: Danaparoid. A review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia. Drugs. 1997 Dec;54(6):903-24. [Article]
  4. Liu J, Pedersen LC: Anticoagulant heparan sulfate: structural specificity and biosynthesis. Appl Microbiol Biotechnol. 2007 Feb;74(2):263-72. doi: 10.1007/s00253-006-0722-x. Epub 2006 Nov 28. [Article]
  5. 24. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 299-300). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
PubChem Substance
FDA label
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Clinical Trials

Clinical Trials
3TerminatedTreatmentHeparin Induced Thrombocytopenia (HIT)1
Not AvailableCompletedNot AvailableAcute HIT II (Heparin-induced Thrombocytopenia Type II)1


Not Available
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Dosage Forms
Injection, solutionSubcutaneous
SolutionIntravenous; Subcutaneous750 unit / 0.6 mL
Injection, solutionIntravenous; Subcutaneous
Injection, solution750 UI
Not Available
Not Available


Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
Not Available
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available


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Pharmacological action
Positive allosteric modulator
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory a...
Gene Name
Uniprot ID
Uniprot Name
Molecular Weight
52601.935 Da
  1. Liu J, Pedersen LC: Anticoagulant heparan sulfate: structural specificity and biosynthesis. Appl Microbiol Biotechnol. 2007 Feb;74(2):263-72. doi: 10.1007/s00253-006-0722-x. Epub 2006 Nov 28. [Article]

Drug created at September 14, 2010 16:20 / Updated at May 03, 2024 10:14