Anticoagulant drug
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]
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.
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