danaparoid
{{Short description|Anticoagulant drug}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 381459436
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| tradename = Orgaran
| Drugs.com = {{drugs.com|CONS|danaparoid}}
| MedlinePlus = a602007
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| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 308068-55-5
| ATC_prefix = B01
| ATC_suffix = AB09
| PubChem =
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| ChemSpiderID = none
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06754
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = BI6GY4U9CW
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201684
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Danaparoid sodium (Orgaran) is an anticoagulant{{cite journal |vauthors=Hagiwara S, Iwasaka H, Hidaka S, Hishiyama S, Noguchi T |title=Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats |journal=Crit Care |volume=12 |issue=2 |pages=R43 |year=2008 |pmid=18380908 |pmc=2447588 |doi=10.1186/cc6851 |doi-access=free }} 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.{{cite journal |vauthors=de Pont AC, Hofstra JJ, Pik DR, Meijers JC, Schultz MJ |title=Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study |journal=Crit Care |volume=11 |issue=5 |pages=R102 |year=2007 |pmid=17854496 |doi=10.1186/cc6119 |pmc=2556745 |doi-access=free }} 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{{cite journal |vauthors=Schindewolf M, Magnani HN, Lindhoff-Last E |title=[Danaparoid in pregnancy in cases of heparin intolerance - use in 59 cases] |language=de |journal=Hamostaseologie |volume=27 |issue=2 |pages=89–97 |date=May 2007 |pmid=17479171 |url=http://www.schattauer.de/index.php?id=1268&pii=ha07020089&no_cache=1}}{{cite journal |vauthors=Magnani HN, Gallus A |title=Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004 |journal=Thromb. Haemost. |volume=95 |issue=6 |pages=967–81 |date=June 2006 |pmid=16732376 |doi=10.1160/TH05-07-0489 |url=http://www.schattauer.de/index.php?id=1268&pii=th06060967&no_cache=1}} (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] [http://www.esra-learning.com/ (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 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|date=December 2021}}
It has also been used in Kasabach–Merritt syndrome in 3 cases.{{cite journal |vauthors=Ontachi Y, Asakura H, Omote M, Yoshida T, Matsui O, Nakao S |title=Kasabach-Merritt syndrome associated with giant liver hemangioma: the effect of combined therapy with danaparoid sodium and tranexamic acid |journal=Haematologica |volume=90 Suppl |pages=ECR29 |date=November 2005 |pmid=16266920 |url=http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=16266920}}
Discontinuation
On August 14, 2002, this drug was withdrawn by Organon International.{{cite web |url=http://www.mayoclinic.com/health/drug-information/DR600517 |title=Danaparoid (Subcutaneous Route) - MayoClinic.com |access-date=2007-08-23 }} 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
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 [Chong 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
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