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      In vitro investigation of the effects of exogenous sugammadex on coagulation in orthopedic surgical patients

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          Abstract

          Background

          Previous studies have shown that sugammadex resulted in the prolongation of prothrombin time and activated partial thromboplastin time. In this study, we aimed to investigate the in vitro effects of exogenous sugammadex on the coagulation variables of whole blood in healthy patients who underwent orthopedic surgery.

          Methods

          The effects of sugammadex on coagulations were assessed using thromboelastography (TEG) in kaolin-activated citrated blood samples taken from 14 healthy patients who underwent orthopedic surgery. The in vitro effects of three different concentrations of sugammadex (42, 193, and 301 μg mL − 1) on the TEG profiles were compared with those of the control (0 μg mL − 1). Previous studies indicated that these exogenous concentrations correspond to the approximate maximum plasma concentrations achieved after the administration of 4, 16, and 32 mg kg − 1 sugammadex to healthy subjects.

          Results

          Increased sugammadex concentrations were significantly associated with reduced coagulation, as evidenced by increases in reaction time (r), coagulation time, and time to maximum rate of thrombus generation (TMRTG), and decreases in the angle, maximum amplitude, and maximum rate of thrombus generation. Compared with the control, the median percentage change (interquartile range) in the TEG values of the samples treated with the highest exogenous sugammadex concentration was the greatest for r, 53% (26, 67.3%), and TMRTG, 48% (26, 59%).

          Conclusions

          This in vitro study suggests that supratherapeutic doses of exogenous sugammadex might be associated with moderate hypocoagulation in the whole blood of healthy subjects.

          Trial registration

          identifier:  UMIN000029081, registered 11 September 2017.

          Related collections

          Most cited references 18

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          Use of Thromboelastography (TEG) for Detection of New Oral Anticoagulants.

          The clinical introduction of new oral anticoagulants (NOACs) has stimulated the development of tests to quantify the effects of these drugs and manage complications associated with their use. Until recently, the only treatment choices for the prevention of venous thromboembolism in orthopedic surgical patients, as well as for stroke and systemic embolism in patients with atrial fibrillation, were vitamin K antagonists, antiplatelet drugs, and unfractionated and low-molecular-weight heparins. With the approval of NOACs, treatment options and consequent diagnostic challenges have expanded.
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            Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients.

            Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables.
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              In normal controls, both age and gender affect coagulability as measured by thrombelastography.

              Our objective was to analyze the effects of age, gender, and the use of oral contraceptives (OCs) on coagulation using thrombelastography (TEG), a single test to analyze both plasma coagulation factors and cellular elements in whole blood. TEG variables were measured in native whole blood and in recalcified citrated blood from 120 healthy adults (60 men and 60 women) with various ages and in an additional 29 healthy women using OCs. We observed hypercoagulability in women compared with men and in women using OCs compared with age-matched nonusers. Moreover, we found hypercoagulability with aging. Using the method of Bland and Altman (Lancet 1986;1:307-10), we demonstrated no correlation between TEG measurements in native and recalcified citrated blood. Aging, female gender, use of OCs, and low-normal hematocrit levels have significant procoagulant effects. TEG measurements in native and recalcified citrated blood are not interchangeable, as indicated by differences between the 2 measurements ranging from 20% in maximal amplitude to 246% in clotting time. Furthermore, the limits of agreement strongly exceeded clinical acceptability to conclude interchangeability.
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                Author and article information

                Contributors
                iloklee@korea.ac.kr
                stelios@naver.com
                chelenh@gmail.com
                heezookim@hotmail.com
                bglim9205@korea.ac.kr
                midoyee@gmail.com
                Journal
                BMC Anesthesiol
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central (London )
                1471-2253
                24 May 2018
                24 May 2018
                2018
                : 18
                Affiliations
                ISNI 0000 0004 0474 0479, GRID grid.411134.2, Department of Anesthesiology and Pain Medicine, , Korea University Guro Hospital, Korea University College of Medicine, ; Seoul, Republic of Korea
                Article
                519
                10.1186/s12871-018-0519-3
                5968558
                29793426
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Anesthesiology & Pain management

                blood coagulation, sugammadex, thromboelastography

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