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Activation of Prekallikrein by Contaminated Heparins, Isolated Contaminant and Related Hypersulfated Chondroitin Sulfate Preparations: Pharmacologic Implications
Author(s) -
Hoppensteadt Debra,
Iqbal Omer,
Messmore Harry,
Adiguzal Cafer,
Bansal Vinod,
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.575.2
Subject(s) - dermatan sulfate , prekallikrein , chemistry , chondroitin sulfate , heparin , chondroitin , sulfation , kallikrein , glycosaminoglycan , whole blood , sulfate , chromatography , biochemistry , pharmacology , medicine , organic chemistry , enzyme
Use of heparins contaminated (CH) with oversulfated chondroitin sulfate (OSCS) has been associated with severe adverse events. Studies were designed to determine the effect of OSCS on the generation of kallikrein (K). CH, a contaminant free heparin (CFH), OSCSs isolated from different heparins, hemisynthetic chondroitin sulfate preparations (HCS), chondroitin sulfate (CS), dermatan sulfate (DS), and mucopolysaccharide polysulfate (MPS) were compared at concentrations up to 1 mg/ml following supplementation to human plasma or whole blood (citrated or hirudinized ). K activity was measured using a specific chromogenic substrate. At a concentration of 100 µg/ml, in citrated plasma OSCS preparations produced the strongest activation of prekallikrein (>0.75/15 mins). CH produced a weaker activity (0.32/15 mins) that was comparable to that produced by CFH (0.24/15 mins). MPS also produced strong activation of prekallikrien into K. In citrated whole blood HCS‐1, HCS‐2, the three HCs and MPS produced a strong generation of K (>1.5/5 mins). CH produced a weaker effect (1.3/5 mins) whereas CFH was much less (0.25/ 5 mins). DS also produced a measurable generation of K (1.2/ 5 mins). CS produced weaker effects (0.6/ 5 mins). In hirudinized whole blood, all agents produced sizable generation of K (>1.5/5 mins). These studies demonstrate that the generation of K is a nonspecific effect of sulfated glycosaminoglycans.