Danaparoid

Danaparoid sodium (Orgaran) is an anticoagulant 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 devoid of heparin. It consists of a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate. 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 (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) 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 in 3 cases.

Discontinuation

On August 14, 2002, this drug was withdrawn by Organon International. 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, due to a low level of structural similarity between danaparoid and heparin, 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 exacerbations, due to allergies to sulfites contained within the medicine (no case has been reported to date).

References

External links

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{{Antithrombotics

Heparins