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Further Studies on the Isolation and Characterization of Heparin Contaminants Isolated From Recalled Batches of Unfractionated Heparin
Author(s) -
Fareed Jawed,
Hoppensteadt Debra,
Jeske Walter,
Walenga Jeanine M,
Bansal Vinod,
Ramacciotti Eduardo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1115.18
Subject(s) - heparin , dermatan sulfate , chemistry , chondroitin sulfate , heparan sulfate , contamination , sulfate , glycosaminoglycan , depolymerization , chromatography , environmental chemistry , biochemistry , organic chemistry , biology , ecology
The main contaminant from the recalled batches of unfractionated heparin (UFH) during the heparin crisis in 2008–2009 was reported to be oversulfated chondroitin sulfate (OSCS). Numerous reports have suggested the presence of other contaminants such as the oversulfated dermatan sulfate, oversulfated heparan sulfate and other non‐heparin GAGs. To further investigate the composition of non‐heparin GAG contaminants, a nitrous acid depolymerization method with stepwise methanolic precipitation was employed. The isolated non‐heparin GAGs from different batches were analyzed for the molecular and structural profile and biologic activities including anticoagulant, antiprotease and protease activation properties. Additional studies were carried out on the antithrombotic, bleeding and hemodynamic effects of these contaminants The interaction of the contaminants with heparin binding proteins were studied using surface enhanced laser desorption ionization methods. Differences in the molecular profile and structural composition were noted. Based on the structural analysis, non‐OSCS GAGs were also found to be present. In most instances OSCS was the main contaminant, however other non‐heparin GAGs were also found to be present in some of the batches. Additional characterization of the contaminants in the recalled batches of UFH is warranted to fully understand the composition of these contaminants.