Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

Marco Guerrini; Daniela Beccati; Zachary Shriver; Annamaria Naggi; Karthik Viswanathan; Antonella Bisio; Ishan Capila; Jonathan C. Lansing; Sara Guglieri; Blair Fraser; Ali Al-Hakim; Nur Sibel Gunay; Zhenqing Zhang; Luke Robinson; Lucinda Buhse; Moheb Nasr; Janet Woodcock; Robert Langer; Ganesh Venkataraman; Robert J. Linhardt; Benito Casu; Giangiacomo Torri; Ram Sasisekharan

doi:10.1038/nbt1407

Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

Marco Guerrini, Daniela Beccati, Zachary Shriver, Annamaria Naggi, Karthik Viswanathan, Antonella Bisio, Ishan Capila, Jonathan C. Lansing, Sara Guglieri, Blair Fraser, Ali Al-Hakim, Nur Sibel Gunay, Zhenqing Zhang, Luke Robinson, Lucinda Buhse, Moheb Nasr, Janet Woodcock, Robert Langer, Ganesh Venkataraman, Robert J. LinhardtBenito Casu, Giangiacomo Torri, Ram Sasisekharan

Research output: Contribution to journal › Article › peer-review

564 Scopus citations

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 β1→3 to a β-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.

Original language	English
Pages (from-to)	669-675
Number of pages	7
Journal	Nature Biotechnology
Volume	26
Issue number	6
DOIs	https://doi.org/10.1038/nbt1407
State	Published - Jun 2008
Externally published	Yes

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Guerrini, M., Beccati, D., Shriver, Z., Naggi, A., Viswanathan, K., Bisio, A., Capila, I., Lansing, J. C., Guglieri, S., Fraser, B., Al-Hakim, A., Gunay, N. S., Zhang, Z., Robinson, L., Buhse, L., Nasr, M., Woodcock, J., Langer, R., Venkataraman, G., ... Sasisekharan, R. (2008). Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nature Biotechnology, 26(6), 669-675. https://doi.org/10.1038/nbt1407

@article{cf5f264e99e74cd7b69912988c0aa316,

title = "Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events",

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 β1→3 to a β-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.",

author = "Marco Guerrini and Daniela Beccati and Zachary Shriver and Annamaria Naggi and Karthik Viswanathan and Antonella Bisio and Ishan Capila and Lansing, {Jonathan C.} and Sara Guglieri and Blair Fraser and Ali Al-Hakim and Gunay, {Nur Sibel} and Zhenqing Zhang and Luke Robinson and Lucinda Buhse and Moheb Nasr and Janet Woodcock and Robert Langer and Ganesh Venkataraman and Linhardt, {Robert J.} and Benito Casu and Giangiacomo Torri and Ram Sasisekharan",

year = "2008",

month = jun,

doi = "10.1038/nbt1407",

language = "English",

volume = "26",

pages = "669--675",

journal = "Nature Biotechnology",

issn = "1087-0156",

publisher = "Nature Publishing Group",

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Guerrini, M, Beccati, D, Shriver, Z, Naggi, A, Viswanathan, K, Bisio, A, Capila, I, Lansing, JC, Guglieri, S, Fraser, B, Al-Hakim, A, Gunay, NS, Zhang, Z, Robinson, L, Buhse, L, Nasr, M, Woodcock, J, Langer, R, Venkataraman, G, Linhardt, RJ, Casu, B, Torri, G & Sasisekharan, R 2008, 'Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events', Nature Biotechnology, vol. 26, no. 6, pp. 669-675. https://doi.org/10.1038/nbt1407

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T1 - Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

AU - Guerrini, Marco

AU - Beccati, Daniela

AU - Shriver, Zachary

AU - Naggi, Annamaria

AU - Viswanathan, Karthik

AU - Bisio, Antonella

AU - Capila, Ishan

AU - Lansing, Jonathan C.

AU - Guglieri, Sara

AU - Fraser, Blair

AU - Al-Hakim, Ali

AU - Gunay, Nur Sibel

AU - Zhang, Zhenqing

AU - Robinson, Luke

AU - Buhse, Lucinda

AU - Nasr, Moheb

AU - Woodcock, Janet

AU - Langer, Robert

AU - Venkataraman, Ganesh

AU - Linhardt, Robert J.

AU - Casu, Benito

AU - Torri, Giangiacomo

AU - Sasisekharan, Ram

PY - 2008/6

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N2 - 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 β1→3 to a β-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.

AB - 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 β1→3 to a β-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.

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JO - Nature Biotechnology

JF - Nature Biotechnology

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ER -

Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

Abstract

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