title: Review: contaminants in heparin: review of the literature, molecular profiling, and clinical implications.
abstract: BACKGROUND
  The contaminant isolated from contaminated heparin was oversulfated chondroitin sulfate (OSCS). Other possible contaminants should be evaluated.
  
  
  METHODS
  Contaminants were isolated from recalled contaminated heparin and were compared to OSCS from animal sources and to heparin by-products synthetically persulfated.
  
  
  RESULTS
  A great variability in molecular weight was observed in the isolated contaminants. Dermatan sulfate with high-molecular-weight in addition to OSCS was detected. Oversulfated chondroitin sulfate from different sources as well as heparin by-products produced activation of prekallikrein to kallikrein at variable rates as measured by the generation of kallikrein. All agents produced activation of the complement system. All compounds formed complexes with platelet factor 4 (PF4) and all produced (14)C serotonin release in the heparin-induced thrombocytopenia (HIT) analysis. The agents also exhibited variable anticoagulant responses that were mostly mediated via heparin cofactor II.
  
  
  CONCLUSIONS
  These results suggest that heparin contaminants represent a heterogeneous group of oversulfated glycosaminoglycans (OSGAGs) which may mediate multiple pathophysiologic responses.
authors.affiliation: Department of Pathology and Pharmacology, Cardiovascular Institute, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ramacciotti
authors.forename: Melanie
authors.initials: M
authors.lastname: Clark
authors.forename: Nasir
authors.initials: N
authors.lastname: Sadeghi
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: Indermohan
authors.initials: I
authors.lastname: Thethi
authors.forename: Marise
authors.initials: M
authors.lastname: Gomes
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000032:analysis* / Q000627:therapeutic use; D002809:Chondroitin Sulfates / Q000009:adverse effects* / Q000032:analysis* / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects; D003871:Dermatan Sulfate / Q000009:adverse effects* / Q000032:analysis* / Q000494:pharmacology; D004340:Drug Contamination; D004789:Enzyme Activation / Q000187:drug effects; D006493:Heparin; D006801:Humans; D010978:Platelet Factor 4 / Q000378:metabolism; D011288:Prekallikrein / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D003871:Dermatan Sulfate; D012701:Serotonin; D010978:Platelet Factor 4; D006493:Heparin; D002809:Chondroitin Sulfates; D011288:Prekallikrein