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      Anticoagulation Management and Monitoring during Pediatric Extracorporeal Life Support: A Review of Current Issues

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          Abstract

          Anticoagulation is an imperfect science and is even more complicated in neonates and young children. The addition of the extracorporeal life support (ECLS) foreign circuit adds an additional layer of complexity. Anticoagulation goals during ECLS are to maintain a clot-free circuit and a hemostatically balanced patient. Unfractionated heparin (UFH) is the default gold standard anticoagulant as no large studies have been performed on any other anticoagulants. This review will focus on the advantages and disadvantages of the various methods to monitor UFH anticoagulation, discuss alternative anticoagulants, and examine bleeding and thrombotic complications during ECLS.

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          Most cited references40

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          Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices.

          Perioperative monitoring of blood coagulation is critical to better understand causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography, rotation thrombelastometry, and Sonoclot analysis, may overcome several limitations of routine coagulation tests in the perioperative setting. The advantage of these techniques is that they have the potential to measure the clotting process, starting with fibrin formation and continue through to clot retraction and fibrinolysis at the bedside, with minimal delays. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Viscoelastic POC coagulation devices are increasingly being used in clinical practice, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states, guiding pro- and anticoagulant therapies, and in diagnosing of a surgical bleeding. A surgical etiology of bleeding has to be considered when viscoelastic test results are normal. In summary, viscoelastic POC coagulation devices may help identify the cause of bleeding and guide pro- and anticoagulant therapies. To ensure optimal accuracy and performance, standardized procedures for blood sampling and handling, strict quality controls and trained personnel are required.
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            Development of the human coagulation system in the full-term infant.

            The investigation of many hemostatic defects in the newborn is limited by the lack of normal reference values. This study was designed to determine the postnatal development of the human coagulation system in the healthy full-term infant. Consecutive mothers of healthy full-term infants born at St Joseph's Hospital in the city of Hamilton were approached for consent. One hundred eighteen full-term infants (37 to 42 weeks' gestational age) were entered into the study. Demographic information and a 2-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 79 full-term infants were studied on each day for each of the coagulation tests. Plasma was fractionated and stored at -70 degrees C for batch assaying of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, and factor assays (biologic): fibrinogen, II, V, VII, VIII, IX, X, XI, XII, and high-molecular weight kininogen. Factor XIII subunits A and S, von Willebrand factor, and the inhibitors antithrombin III, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C, and protein S were measured immunologically. Plasminogen, prekallikrein, and heparin cofactor II were measured by using chromogenic substrates. The large number of infants studied at each time point allowed us to determine the following: the range of normal for each test at five time points in the postnatal period; that coagulation tests vary with the postnatal age of the infant; that different coagulation factors show different postnatal patterns of maturation; and that near-adult values are achieved for most components by 6 months of life. In summary, this large cohort of infants studied consecutively in the postnatal period allowed us to determine the normal development of the human coagulation system in the full-term infant.
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              Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey.

              The objective of this study was to determine current practices of anticoagulation in patients on extracorporeal membrane oxygenation. Internet-based cross-sectional survey distributed between November 2010 and May 2011. Extracorporeal Life Support Organization-registered extracorporeal membrane oxygenation centers internationally. : Extracorporeal membrane oxy genation medical directors and coordinators. None. There were 121 responses from extracorporeal membrane oxy genation medical directors and coordinators at 187 Extracorporeal Life Support Organization centers with access to the survey. Eighty-four of 117 (72%) respondents reported having a written institutional extracorporeal membrane oxy genation protocol for both anticoagulation and blood product management at their institutions. Sixty-nine of 117 (59%) respondents reported use of tip-to-tip or partially heparin-bonded circuits. Unfractionated heparin was used at all centers; only 8% of respondents indicated use of alternative anticoagulation medications in the six months prior to the survey. The preferred method of anticoagulation monitoring was the serial measurement of activated clotting time, as reported by 97% of respondents. In this survey, 82% of respondents reported antithrombin III testing, 65% reported anti-factor Xa testing, and 43% reported use of thromboelastography during extracorporeal membrane oxy genation. Goal ranges for these three tests and interventions triggered by out-of-range values were found to be variable. Extracorporeal membrane oxy genation anticoagulation management policies vary widely by center. The majority of extracorporeal membrane oxy genation programs employ activated clotting time as the preferred anticoagulation monitoring tool. The coagulation system is also monitored using more specific markers such as antithrombin III, anti-factor Xa, and thromboelastography by a large number of centers. Future research is needed to elucidate optimal anticoagulation management and improve outcomes.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/340153
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                22 June 2016
                2016
                : 4
                : 67
                Affiliations
                [1] 1Pediatric Critical Care, Stollery Children’s Hospital , Edmonton, AB, Canada
                Author notes

                Edited by: Antonio Francesco Corno, Glenfield Hospital, UK

                Reviewed by: Patrick O. Myers, Geneva University Hospitals, Switzerland; Meena Nathan, Boston Children’s Hospital, USA

                *Correspondence: Lindsay M. Ryerson, ryerson@ 123456ualberta.ca

                Specialty section: This article was submitted to Pediatric Cardiology, a section of the journal Frontiers in Pediatrics

                Article
                10.3389/fped.2016.00067
                4916162
                27446890
                9755545e-c48b-4879-b30a-19a8c7d3324e
                Copyright © 2016 Ryerson and Lequier.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 April 2016
                : 10 June 2016
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 45, Pages: 7, Words: 5568
                Categories
                Pediatrics
                Review

                pediatrics,anticoagulation,extracorporeal life support,heparin,bleeding

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