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Oversulfated Chondroitin Sulfate Increases the Antithrombotic and Bleeding Effects of Heparin
Author(s) -
Litinas Evangelos,
Adiguzal Cafer,
Jeske Walter,
Hoppensteadt Debra,
Messmore Harry L.,
Walenga Jeanine M.,
Fareed Jawed
Publication year - 2009
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.23.1_supplement.569.8
Subject(s) - antithrombotic , heparin , chondroitin sulfate , anticoagulant , chemistry , ex vivo , pharmacology , medicine , biochemistry , in vitro , glycosaminoglycan
Earlier this year batches of unfractionated heparin (UFH) were recalled due to the presence of oversulfated chondroitin sulfate (OSCS). While structural and molecular characteristics of the contaminant are reported, no data on antithrombotic and bleeding effects is available. This investigation characterizes the effects of OSCS on the safety and efficacy of contaminated heparin (CH) in animal models. CH (Baxter; lot 117050) and contaminant free UFH (CFH) (Abraxis; lot 405651) were studied using rat jugular vein clamping induced thrombosis and rat tail transaction models. Ex vivo studies were carried out to measure anticoagulant and anti‐Xa effects. CH contained 30% OSCS; CFH did not contain OSCS. In the bleeding studies, no differences between CH (37.0± .5 min.) and CFH (35.0±5.7 min) were observed at a dose of 2 mg/kg. At 5mg/kg, CH (67.8±1.8 min.) produced stronger bleeding effects than CFH (57.1±1.9 mi.). In the jugular vein clamping model, CH produced stronger antithrombotic effects (6.2±1.2 vs. 5.2±0.3 clampings) at 2mg/kg and at 5 mg/kg (7.6±0.8 clampings vs. 6.2±0). Ex vivo analysis showed a stronger anticoagulant effect with the CH. Anti‐Xa and anti‐IIa activities were higher in the CH groups. It appears that the presence of the OSCS contaminant augmented the anticoagulant and bleeding effects of CH and may have contributed to the increased clinical bleeding observed in patients treated with these agents.