Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin.
In 2008, oversulfated chondroitin sulfate (OSCS) was identified as the main contaminant in recalled heparin. Oversulfated chondroitin sulfate can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin and may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the interactions of various OSCSs on heparin in animal models of thrombosis and bleeding, as well as on the anticoagulant and antiprotease effects in in vitro assays. Mixtures of 70% unfractionated heparin (UFH) with 30% OSCS from different sources were tested. In the in vitro activated partial thromboplastin time (aPTT) assay, all contaminant mixtures showed a decrease in clotting times. In addition, a significant increase in bleeding time compared to the control (UFH/saline) was observed. In the thrombosis model, no significant differences were observed. The OSCSs significantly increased anti-Xa activity in ex vivo blood samples. These results indicate that various sources of OSCS affect the hemostatic properties of heparin.
Department of Pharmacology, Loyola University Chicago, IL, USA.
Angel
A
Gray
Evangelos
E
Litinas
Walter
W
Jeske
Jawed
J
Fareed
Debra
D
Hoppensteadt
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D002417:Cattle; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004340:Drug Contamination; D004347:Drug Interactions; D056736:Drug Recalls; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007601:Jugular Veins; D008297:Male; D011516:Prothrombin / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012754:Sharks; D012860:Skates, Fish; D013045:Species Specificity; D013431:Sulfates / Q000032:analysis; D013552:Swine; D013927:Thrombosis / Q000517:prevention & control; D014020:Tissue Extracts / Q000737:chemistry
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D013431:Sulfates; D014020:Tissue Extracts; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D002809:Chondroitin Sulfates