Danaparoid sodium (Orgaran) is an

anticoagulant 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 t ...

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. euleman DG. Haemostasis 1992;22:58-65 and Ofosu FA Haemostasis 1992;22:66-72 Danaparoid is a low molecular weight

heparinoid 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 ...

devoid of

heparin 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 treat ...

. It consists of a mixture of

heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...

dermatan sulfate Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. It is also referred to as chondroitin sulfate B, although it is no longer class ...

, and

chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have ove ...

. 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. hromb Haemostas 1987;57/3:286-93to 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 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 ...

(HIT) which may otherwise cause

paradoxical thrombosis An embolus, is described as a free-floating mass, located inside blood vessels that can travel from one site in the blood stream to another. An embolus can be made up of solid (like a blood clot), liquid (like amniotic fluid), or gas (like air). O ...

. 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) agnani HN & Wester JPJ. Open access Scientific Reports 2012;1/9:423-9renal replacement therapy and in patients with hepatic disorders associated with cirrhosis such as portal vein thrombosis ujiyama et al. BMC Gatsroenterol 2017;17:112-20and the sinusoidal obstruction syndrome ato et al. Pediatr Transplant 2017;e13099and thrombotic micro-angiopathy achida et al. Bone Marrow Transplant 2016;1-3 Doi:10.1038/bmt.2016.270that occur after haemopoietic stem-cell transplantation in patients with haematogenous and solid malignancies. It has also been used in

Kasabach–Merritt syndrome Kasabach–Merritt syndrome, also known as hemangioma with thrombocytopenia, is a rare disease, usually of infants, in which a vascular tumor leads to decreased platelet counts and sometimes other bleeding problems, which can be life-threatenin ...

in 3 cases.

Discontinuation

On August 14, 2002, this drug was withdrawn by

Organon International Organon & Co. is an American pharmaceutical company headquartered in Jersey City, New Jersey. Organon specializes in the following core therapeutic fields: reproductive medicine, contraception, psychiatry, hormone replacement therapy (HRT), a ...

. 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."Heparin Induced Thrombocytopenia" Uptodate www.uptodate.com retrieved on 2/6/2009 The drug is now owned and distributed by Aspen Pharma.

Administration

IV and SC

Side effects

* Bleeding (solely restricted to patients undergoing cardio-pulmonmary surgery with by pass) found in 4.6% of medical patients, 6.1% after major general and vascular surgery, but 42.3% after CPBS (due to lack of an effective antidote) for which it is now contraindicated. *

Low platelets Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

, due to a low level of structural similarity between danaparoid and

, i.e.only in some patients sensitive to heparin or a LMWH but to date never developed spontaneously. Platelet count recovery was more frequent than in the control group in 2 comparative studies in patients with HIT hong et al. Thromb Haemost 2001;86:1170-1175 and Lubenow et al. Thromb Res 2006;117:507-15* Possibly

Asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

exacerbations, due to allergies to

sulfite Sulfites or sulphites are compounds that contain the sulfite ion (or the sulfate(IV) ion, from its correct systematic name), . The sulfite ion is the conjugate base of bisulfite. Although its acid ( sulfurous acid) is elusive, its salts are w ...

s contained within the medicine (no case has been reported to date).

References

External links

* {{Antithrombotics Heparins