![]() Allergy to fish may predispose to this acute response, because commercial protamine originates from sperm of salmon fished around Japan. Thus, in the USA alone more than one thousand life-threatening complications a year could be attributed to the toxicity of protamine. Although in 2010 these numbers decreased by 15% due to more frequent percutaneous interventions, protamine usage increased in vascular surgery, such as fistula placement, abdominal aortic aneurysm repair, and other open abdominal surgeries, or transcatheter aortic valve implantations. In 2003 666,000 open-heart surgeries and 470,000 Coronary Artery Bypass Graft (CABG) procedures were performed within the USA. According to reports the incidence of protamine-related anaphylaxis varies from 0.2 to 10%. predicted that 7% of these patients may die anyway because of serious side effects of protamine, such as anaphylactic shock, pulmonary vasoconstriction or systemic hypotension. After surgery almost all patients have to receive protamine: a cationic protein inactivating heparin and restoring coagulation most would probably bleed to death without this antidote. It enables open-heart surgery by preventing blood clotting in the heart-lung machine (cardiopulmonary bypass) oxygenating and supplying blood to the main body organs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.Īlthough many new antithrombotic agents were introduced in the last few years, unfractionated heparin (UFH), an anionic polysaccharide, remains a key drug inhibiting blood coagulation in case of emergency. ![]() KK, KS, and MN acknowledge the financial support of the Foundation for Polish Science Team Programme co-financed by the EU European Regional Development Fund, PolyMed, TEAM/2008-2/6. KK was supported by National Science Centre Grant No. BK was supported by funds from Leading National Research Center in Bialystok (31/KNOW/2013). ![]() This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: The study was supported by National Science Centre Grant No. 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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