Heparin-Binding Copolymer As a Complete Antidote for Low-Molecular-Weight Heparins in Rats
1521-0103/373/1/51–61$35.00 https://doi.org/10.1124/jpet.119.262931 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 373:51–61, April 2020 Copyright ª 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. Heparin-Binding Copolymer as a Complete Antidote for Low-Molecular-Weight Heparins in Rats Bartlomiej Kalaska, Joanna Miklosz, Kamil Kaminski, Justyna Swieton, Aleksandra Jakimczuk, Shin-Ichi Yusa, Dariusz Pawlak, Maria Nowakowska, Krzysztof Szczubiałka, and Andrzej Mogielnicki Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.); Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.); and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.) Received September 30, 2019; accepted January 9, 2020 Downloaded from ABSTRACT Bleeding resulting from the application of low-molecular-weight in vitro by all LMWHs with an optimal weight ratio of 2.5:1. The heparins (LMWHs) may be treated with protamine sulfate, but complexes of HBC-LMWHs were below 5 mm. We observed this treatment lacks efficiency; its action against antifactor Xa no effects on the viability of cardiovascular cells treated with jpet.aspetjournals.org activity is limited to ∼60%. Moreover, protamine sulfate can HBC at concentrations up to 0.05 mg/ml. Single doses up to cause life-threatening hypersensitivity reactions. We developed 20 mg/kg of HBC were well tolerated by rats. HBC completely diblock heparin-binding copolymer (HBC), which can neutralize reversed the effects of LMWHs on bleeding time and anti- the anticoagulant activity of parenteral anticoagulants.
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