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Nat Biotechnol. 2008 Jun;26(6):669-75. doi: 10.1038/nbt1407. Epub 2008 Apr 23.

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

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  • 1Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Città Studi, via Giuseppe, Colombo 81, 20133 Milan, Italy.


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.

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