Oversulfated Chondroitin Sulfate is a major contaminant in Heparin associated with Adverse Clinical Events

Authors
Guerrini, M.
Beccati, D.
Shriver, Z.
Naggi, A.M.
Bisio, A.
Capila, I.
Lansing, J.
Guglieri, S.
Fraser, B.
Al-Hakim, A.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2008
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Full Citation
Oversulfated Chondroitin Sulfate is a major contaminant in Heparin associated with Adverse Clinical Events, M. Guerrini, D. Beccati, Z. Shriver, A. M. Naggi, A. Bisio, I. Capila, J. Lansing, S. Guglieri, B. Fraser, A. Al-Hakim, S. Gunay, K. Viswanathan, Z. Zhang, L. Robinson, G. Venkataraman, L. Buhse, M. Nasr, J. Woodcock, R. Langer, R. Linhardt, B. Casu, G. Torri, R. Sasisekharan, Nature Biotechnology, 26, 669-775, 2008.
Abstract
Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.
Description
Nature Biotechnology, 26, 669-775
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Nature
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The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
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