Danaparoid

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Danaparoid
Clinical data
Trade names Orgaran
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MedlinePlus a602007
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Danaparoid sodium (Orgaran) is an anticoagulant [1] with an antithrombotic action due to inhibition of thrombin generation (TGI) by two mechanisms: indirect inactivation of Factor Xa via AT and direct inhibition of thrombin activation of Factor IX (an important feedback loop for thrombin generation). It also possesses a minor anti-thrombin activity, mediated equally via AT and Heparin Co-factor II producing a ratio of anti-Xa:IIa activity >22. [Meuleman DG. Haemostasis 1992;22:58-65 and Ofosu FA Haemostasis 1992;22:66-72]

Contents

Danaparoid is a low molecular weight heparinoid devoid of heparin. It consists of a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate. [2] It is chemically distinct from heparin, has different protein-binding properties because of its low degree of sulphation and low surface charge density and thus has little cross-reactivity in heparin-intolerant patients.

The TGI activity, considered by Fernandes et al. [Thromb Haemostas 1987;57/3:286-93] to provide an index of antithrombotic potential, of danaparoid has a half-life of 6.7 hours.

Uses

It is used to prevent deep venous clots, particularly in situations with a high risk of clot formation, such as after hip surgery.

It is also used as a heparin substitute in heparin-induced thrombocytopenia [3] [4] (HIT) which may otherwise cause paradoxical thrombosis. Danaparoid is used for thrombosis prophylaxis and treatment in heparin-induced thrombocytopenia patients. Although pre-treatment serological cross-reactivity with heparin-induced antibodies can occur in 5.2% of the patients it bears no systematic relationship with clinical cross-reactivity, 3.2% in the same study of 1478 patients with acute HIT [Magnani & Gallus Thromb Haemost 2006;95:967-81] (ESRA).

It is also approved for the treatment of DIC in Japan and although not approved for the following it has shown efficacy and safety in 406 case reports of paediatric use [Bidlingmaier et al. Acta Haematologica 2006;115:237-247], pregnancy [see Magnani HN. Thromb Res 2010;125:297-302] 197 cases & 81 additional uses to protect cesarian section, patients in renal failure requiring intermittent [Magnani HN. Thromb Res 2010;125:e171-e176] or continuous (CVVRT) [Magnani HN & Wester JPJ. Open access Scientific Reports 2012;1/9:423-9] renal replacement therapy and in patients with hepatic disorders associated with cirrhosis such as portal vein thrombosis [Fujiyama et al. BMC Gatsroenterol 2017;17:112-20] and the sinusoidal obstruction syndrome [Kato et al. Pediatr Transplant 2017;e13099] and thrombotic micro-angiopathy [Machida et al. Bone Marrow Transplant 2016;1-3 Doi:10.1038/bmt.2016.270] that occur after haemopoietic stem-cell transplantation in patients with haematogenous and solid malignancies. [ citation needed ]

It has also been used in Kasabach–Merritt syndrome in 3 cases. [5]

Discontinuation

On August 14, 2002, this drug was withdrawn by Organon International. [6] from the US market, due to a shortage in drug substance. The manufacturer has continued providing the medication in all other locales where it is approved for marketing. [7]

The drug is now owned and distributed by Aspen Pharma.

Administration

IV and SC

Side effects

Related Research Articles

<span class="mw-page-title-main">Anticoagulant</span> Class of drugs

Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they help keep the bite area unclotted long enough for the animal to obtain some blood. As a class of medications, anticoagulants are used in therapy for thrombotic disorders. Oral anticoagulants (OACs) are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. Some anticoagulants are used in medical equipment, such as sample tubes, blood transfusion bags, heart–lung machines, and dialysis equipment. One of the first anticoagulants, warfarin, was initially approved as a rodenticide.

<span class="mw-page-title-main">Heparin</span> Anticoagulant

Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given intravenously or by injection under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines.

<span class="mw-page-title-main">Antithrombin</span> Mammalian protein found in Homo sapiens

Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 464-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. A single glycosylation site remains consistently un-occupied in the minor form of antithrombin, β-antithrombin. Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor IIa (thrombin) and factor Xa.

Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism and in the treatment of myocardial infarction.

<span class="mw-page-title-main">Argatroban</span> Pharmaceutical drug

Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food and Drug Administration (FDA) for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). In 2002, it was approved for use during percutaneous coronary interventions in patients who have HIT or are at risk for developing it. In 2012, it was approved by the MHRA in the UK for anticoagulation in patients with heparin-induced thrombocytopenia Type II (HIT) who require parenteral antithrombotic therapy.

<span class="mw-page-title-main">Fondaparinux</span> Chemical compound

Fondaparinux is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by Viatris. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.

Heparinoids are glycosaminoglycans which are chemically and pharmacologically related to heparin. They include oligosaccharides and sulfated polysaccharides of plant, animal, or synthetic origin. Multiple scientific studies have been conducted on heparinoids.

<span class="mw-page-title-main">Heparin cofactor II</span> Protein-coding gene in the species Homo sapiens

Heparin cofactor II (HCII), a protein encoded by the SERPIND1 gene, is a coagulation factor that inhibits IIa, and is a cofactor for heparin and dermatan sulfate.

<span class="mw-page-title-main">Platelet factor 4</span> Protein involved in blood clotting, wound healing and inflammation

Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine ligand 4 (CXCL4). This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation. It is usually found in a complex with proteoglycan.

Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor.

Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin. Some are in clinical use, while others are undergoing clinical development. Several members of the class are expected to replace heparin and warfarin in various clinical scenarios.

The Trousseau sign of malignancy or Trousseau's syndrome is a medical sign involving episodes of vessel inflammation due to blood clot (thrombophlebitis) which are recurrent or appearing in different locations over time. The location of the clot is tender and the clot can be felt as a nodule under the skin. Trousseau's syndrome is a rare variant of venous thrombosis that is characterized by recurrent, migratory thrombosis in superficial veins and in uncommon sites, such as the chest wall and arms. This syndrome is particularly associated with pancreatic, gastric and lung cancer and Trousseau's syndrome can be an early sign of cancer sometimes appearing months to years before the tumor would be otherwise detected. Heparin therapy is recommended to prevent future clots. The Trousseau sign of malignancy should not be confused with the Trousseau sign of latent tetany caused by low levels of calcium in the blood.

<span class="mw-page-title-main">Ecarin clotting time</span>

Ecarin clotting time (ECT) is a laboratory test used to monitor anticoagulation during treatment with hirudin, an anticoagulant medication which was originally isolated from leech saliva. Ecarin, the primary reagent in this assay, is derived from the venom of the saw-scaled viper, Echis carinatus.

Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis. Pregnancy itself is a factor of hypercoagulability, as a physiologically adaptive mechanism to prevent post partum bleeding. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.

<span class="mw-page-title-main">Bemiparin sodium</span> Chemical compound

Bemiparin is an antithrombotic and belongs to the group of low molecular weight heparins (LMWH).

<span class="mw-page-title-main">Parnaparin sodium</span> Pharmaceutical drug

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<span class="mw-page-title-main">Reviparin sodium</span> Pharmaceutical drug

Reviparin is an antithrombotic and belongs to the group of low molecular weight heparins (LMWH).

Prothrombin G20210A is a genetic condition that increases the risk of blood clots including from deep vein thrombosis, and of pulmonary embolism. One copy of the mutation increases the risk of a blood clot from 1 in 1,000 per year to 2.5 in 1,000. Two copies increases the risk to up to 20 in 1,000 per year. Most people never develop a blood clot in their lifetimes.

<span class="mw-page-title-main">Ciraparantag</span> Chemical compound

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References

  1. Hagiwara S, Iwasaka H, Hidaka S, Hishiyama S, Noguchi T (2008). "Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats". Crit Care. 12 (2): R43. doi: 10.1186/cc6851 . PMC   2447588 . PMID   18380908.
  2. de Pont AC, Hofstra JJ, Pik DR, Meijers JC, Schultz MJ (2007). "Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study". Crit Care. 11 (5): R102. doi: 10.1186/cc6119 . PMC   2556745 . PMID   17854496.
  3. Schindewolf M, Magnani HN, Lindhoff-Last E (May 2007). "[Danaparoid in pregnancy in cases of heparin intolerance - use in 59 cases]". Hamostaseologie (in German). 27 (2): 89–97. PMID   17479171.
  4. Magnani HN, Gallus A (June 2006). "Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004". Thromb. Haemost. 95 (6): 967–81. doi:10.1160/TH05-07-0489. PMID   16732376.
  5. Ontachi Y, Asakura H, Omote M, Yoshida T, Matsui O, Nakao S (November 2005). "Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid". Haematologica. 90 Suppl: ECR29. PMID   16266920.
  6. "Danaparoid (Subcutaneous Route) - MayoClinic.com" . Retrieved 2007-08-23.
  7. "Heparin Induced Thrombocytopenia" Uptodate www.uptodate.com retrieved on 2/6/2009