Subscribe to RSS
DOI: 10.1160/TH09-02-0079
The Tainted Heparin Story: An Update
Financial support: This work was supported in part by the National Institute of Health Grants GM57073 and HL080278.Publication History
Received:
05 February 2009
Accepted after major revision:
09 July 2009
Publication Date:
27 November 2017 (online)
Summary
Recently, certain batches of heparin have been associated with an acute, rapid onset of serious side-effects indicative of allergictype reactions.These reports generated significant concern regarding the possible presence of a dangerous contaminant within heparin and highlighted the need to re-assess the purity criteria of heparin preparations for clinical use. Given the nature of the array of all possible contaminants, traditional screening tests cannot safely differentiate between contaminated and uncontaminated heparin preparations. Monoand bi-dimensional NMR spectroscopy are powerful techniques that are able to detect and quantify a wide variety of potential sulfated polysaccharide contaminants. As such, these techniques are powerful tools for the analysis and assessment of heparin preparations.
-
References
- 1 Contaminant detected in heparin material of specified origin in the USA and in Germany; serious adverse events reported; recall measures initiated. World Health Organization Alert No. 118 (7 March 2008. http://www.who.int/medicines/publications/ drugalerts/Alert_118_Heparin.pdf
- 2 Notice of Recall from Rotexmedica to Bfarm (German Regulatory Authorities. Rotexmedica/Bfarm Notice (7 March 2008. http://www.akdae.de/20/40/Arch- iv/ 2008/20080310.pdf.
- 3 Communication. Information on heparin sodium injection. US Food and Drug Administration. http://www.fda.gov/cder/drug/infopage/heparin/ default.htm.
- 4 Guerrini M, Beccati D, Shriver Z. et al. Oversulfated chondroitinsulfate is a contaminant in heparin associated with adverse clinical events. Nature Biotechnol 2008; 26: 669-675.
- 5 Kishimoto TK, Viswanathan K, Ganguly T. Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl. J Med 2008; 358: 2457-2467.
- 6 Blossom DB, Kallen AJ, Pate PR. et al. Outbreak of adverse reactions associated with contaminated heparin. N Engl J Med 2008; 359: 2674-2684.
- 7 Casu B (2005) Structure and active domains of heparin. In Chemistry and Biology of Heparin and Heparan Sulfate. Garg HG, Linhardt RJ, Hales CA. eds 1-28 Elsevier, Ltd; Oxford, UK.:
- 8 Pharmacopeial Forum. Proposed heparin sodium monograph. [Mar.-Apr. 2009] Vol. 35 (2). http://www. usp.org/hottopics/heparin.html
- 9 Guerrini M, Bisio A, Torri G. Combined quantitative 1H and 13C-NMR spectroscopy for characterization of heparin preparations. Semin. Thromb. Hemostas 2001; 27: 473-482.
- 10 McEwen I, Rundlöf T, Ek M. et al. Effect of Ca2+ on the 1H NMR chemical shift of the methyl signal of oversulphated chondroitin sulphate, a contaminant in heparin. J of Pharm and Biomed Anal 2009; 49: 816-819.
- 11 Guerrini M, Naggi A, Guglieri S. et al. Complex glycosaminoglycans: profiling substitution patterns by two dimensional nmr spectroscopy. Anal Biochem 2005; 337: 35-47.