Different Sources of Over‐Sulfated Chondroitin Sulfate (OSCS) May Produce Differential Interactions with Heparins

Abstract

Use of heparin contaminated with over‐sulfated chondroitin sulfate (OSCS) is associated with adverse reactions. OSCS can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin which may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the effects of various OSCSs on the safety and efficacy of heparin in rat jugular vein thrombosis (JVT) and rat tail bleeding (RTB) models, and the interaction of OSCS with LMWH and ULMWH using in vitro assays. 70/30 mixtures of UFH and OSCS from various sources were tested at 2 mg/kg IV. In the RTB studies, significant differences between the UFH/saline treated rats (21.75±1.13 min) and the UFH/P (28.43±4.58 min), UFH/Sh (28.90±2.70 min), and UFH/S (27.8±2.56 min) treated rats were observed (p<0.05 vs control). In the JVT model, no significant differences were observed. B, P, and S significantly increased the anti‐Xa activity ex vivo (p<0.05). Only 70/30 enoxaparin/OSCS showed an increase in the aPTT, thrombin time, and Heptest assays compared to control. These results indicate that various sources of OSCS do affect the hemostatic properties of heparin differently. Also, OSCS may have an effect on LMWHs, but not ULMWHs.