Danaparoid

 ( Heparins ) 

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. Meuleman

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. Thromb to provide an index of antithrombotic potential, of danaparoid has a half-life of 6.7 hours.

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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 (ESRA) .

It is also approved for the treatment of disseminated intravascular coagulation in Japan and although not approved for the following it has shown efficacy and safety in 406 case reports of paediatric use Bidlingmaier, pregnancy see 197 cases & 81 additional uses to protect cesarian section, patients in renal failure requiring intermittent Magnani or continuous (CVVRT) Magnani renal replacement therapy and in patients with hepatic disorders associated with cirrhosis such as portal vein thrombosis Fujiyama and the sinusoidal obstruction syndrome Kato and thrombotic micro-angiopathy Machida that 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.

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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.

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Administration IV and SC

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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.
• Thrombocytopenia, 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 Chong
• Possibly Asthma exacerbations, due to allergies to contained within the medicine (no case has been reported to date).

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