Authors
Takashi Kei Kishimoto, Karthik Viswanathan, Tanmoy Ganguly, Subbiah Elankumaran, Sean Smith, Kevin Pelzer, Jonathan C Lansing, Nammalwar Sriranganathan, Ganlin Zhao, Zoya Galcheva-Gargova, Ali Al-Hakim, Gregory Scott Bailey, Blair Fraser, Sucharita Roy, Thomas Rogers-Cotrone, Lucinda Buhse, Mark Whary, James Fox, Moheb Nasr, Gerald J Dal Pan, Zachary Shriver, Robert S Langer, Ganesh Venkataraman, K Frank Austen, Janet Woodcock, Ram Sasisekharan
Publication date
2008/6/5
Journal
New England Journal of Medicine
Volume
358
Issue
23
Pages
2457-2467
Publisher
Massachusetts Medical Society
Description
Background
There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred after intravenous heparin administration in the United States and Germany.
Methods
Heparin procured from the Food and Drug Administration, consisting of suspect lots of heparin associated with the clinical events as well as control lots of heparin, were screened in a blinded fashion both for the presence of OSCS and for any biologic activity that could potentially link the contaminant to the observed clinical adverse events. In vitro assays for the activation of the contact system and the complement cascade were performed. In addition, the ability of OSCS to recapitulate key clinical manifestations in vivo was tested in swine.
Results
The OSCS found in contaminated lots of unfractionated …
Total citations
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