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 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.
authors.affiliation: Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Città Studi, via Giuseppe, Colombo 81, 20133 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Guerrini
authors.forename: Daniela
authors.initials: D
authors.lastname: Beccati
authors.forename: Zachary
authors.initials: Z
authors.lastname: Shriver
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.forename: Karthik
authors.initials: K
authors.lastname: Viswanathan
authors.forename: Antonella
authors.initials: A
authors.lastname: Bisio
authors.forename: Ishan
authors.initials: I
authors.lastname: Capila
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Lansing
authors.forename: Sara
authors.initials: S
authors.lastname: Guglieri
authors.forename: Blair
authors.initials: B
authors.lastname: Fraser
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Hakim
authors.forename: Nur Sibel
authors.initials: NS
authors.lastname: Gunay
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Luke
authors.initials: L
authors.lastname: Robinson
authors.forename: Lucinda
authors.initials: L
authors.lastname: Buhse
authors.forename: Moheb
authors.initials: M
authors.lastname: Nasr
authors.forename: Janet
authors.initials: J
authors.lastname: Woodcock
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Ganesh
authors.initials: G
authors.lastname: Venkataraman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Benito
authors.initials: B
authors.lastname: Casu
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.forename: Ram
authors.initials: R
authors.lastname: Sasisekharan
mesh_terms: D002809:Chondroitin Sulfates / Q000032:analysis* / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006493:Heparin / Q000032:analysis* / Q000737:chemistry*; D006801:Humans
chemical_list: D006493:Heparin; D002809:Chondroitin Sulfates