![]() ![]() Received: OctoAccepted: JanuPublished: March 17, 2015Ĭopyright: © 2015 Kalaska et al. PLoS ONE 10(3):Īcademic Editor: Paulo Lee Ho, Instituto Butantan, BRAZIL (2015) Nonclinical Evaluation of Novel Cationically Modified Polysaccharide Antidotes for Unfractionated Heparin. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine.Ĭitation: Kalaska B, Kaminski K, Sokolowska E, Czaplicki D, Kujdowicz M, Stalinska K, et al. Cationic polysaccharides of various structures neutralize UFH. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. ![]() Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. Protamine, the only registered antidote of unfractionated heparin (UFH), may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. ![]()
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