title: Molecular profiling of heparinase-I resistant glycosaminoglycans in contaminated heparins. Comparative studies with uncontaminated heparin and porcine oversulfated chondroitin sulfate.
abstract: OBJECTIVE
  Heparin is a widely used anticoagulant which is usually obtained from porcine mucosal tissue. The structure of heparin is comparable to other naturally occurring glycosaminoglycans such as chondroitin sulfate and dermatan sulfate. The commercially available heparin preparations may contain small amounts of dermatan sulfate as a carry-over impurity. More recently (November 2007 to April 2008), an increased incidence of adverse events and deaths associated with the use of heparin alerted regulatory agencies to investigate the composition of heparin. As a result, oversulfated chondroitin sulfate was found to be the main determinant of the observed adverse reactions. This glycosaminoglycan is not usually found in the mammalian tissues.
  
  
  METHODS
  This investigation reports on the comparison of contaminant free and contaminated heparins and their digestion by heparinase-I. It also describes the molecular profile of the contaminant isolated from the recalled heparin preparations in comparison to oversulfated chondroitin sulfate. The anticoagulant and anti-Xa activities are also reported.
  
  
  RESULTS
  The contaminant is found to be comparable to the synthesized OSCS as both were resistant to heparinase-I digestion. The contaminant and OSCS exhibited weaker anticoagulant activities than heparin and did not have any anti-Xa effects.
  
  
  CONCLUSIONS
  This data strongly suggests that such glycosaminoglycans as chondroitin sulfate can be structurally modified to exhibit anticoagulant activities and their molecular weight can be adjusted to mimic heparin.
authors.affiliation: Department of Pathology and Pharmacology, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Clark
authors.forename: D
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: J
authors.initials: J
authors.lastname: Walenga
authors.forename: L
authors.initials: L
authors.lastname: Myers
authors.forename: J
authors.initials: J
authors.lastname: Cunanan
authors.forename: W
authors.initials: W
authors.lastname: Jeske
authors.forename: C
authors.initials: C
authors.lastname: Adiguzel
authors.forename: O
authors.initials: O
authors.lastname: Iqbal
authors.forename: J
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D001681:Biological Assay; D001777:Blood Coagulation / Q000187:drug effects; D002356:Cartilage; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000494:pharmacology; D004340:Drug Contamination; D004789:Enzyme Activation / Q000187:drug effects; D015951:Factor Xa / Q000187:drug effects; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology; D019763:Heparin Lyase; D006801:Humans; D008970:Molecular Weight; D013552:Swine
chemical_list: D000925:Anticoagulants; D006493:Heparin; D002809:Chondroitin Sulfates; D015951:Factor Xa; D019763:Heparin Lyase