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      Early platelet dysfunction in patients receiving extracorporeal membrane oxygenation is associated with mortality

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          Abstract

          Extracorporeal membrane oxygenation (ECMO) is used for patients with cardiopulmonary failure and is associated with severe bleeding and poor outcome. Platelet dysfunction may be a contributing factor. The aim of this prospective observational study was to characterize platelet dysfunction and its relation to outcome in ECMO patients. Blood was sampled from thirty ECMO patients at three timepoints. Expression of CD62P, CD63, activated GPIIb/IIIa, GPVI, GPIbα and formation platelet-leukocyte aggregates (PLA) were analyzed at rest and in response to stimulation. Delta granule storage-pool deficiency and secretion defects were also investigated. Fifteen healthy volunteers and ten patients with coronary artery disease served as controls. Results were also compared between survivors and non-survivors. Compared to controls, expression of platelet surface markers, delta granule secretion and formation of PLA was reduced, particularly in response to stimulation. Baseline CD63 expression was higher and activated GPIIb/IIIa expression in response to stimulation was lower in non-survivors on day 1 of ECMO. Logistic regression analysis revealed that these markers were associated with mortality. In conclusion, platelets from ECMO patients are severely dysfunctional predisposing patients to bleeding complications and poor outcome. Platelet dysfunction on day 1 of ECMO detected by the platelet surface markers CD63 and activated GPIIb/IIIa is associated with mortality. CD63 and activated GPIIb/IIIa may therefore serve as novel prognostic biomarkers, but future studies are required to determine their true potential.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s11239-021-02562-9.

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          Most cited references36

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          Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.

          Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.
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            Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.

            It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the inter-relationship between these players is completely unknown. We report several cellular events that led to enhanced trapping of bacteria in blood vessels: platelet TLR4 detected TLR4 ligands in blood and induced platelet binding to adherent neutrophils. This led to robust neutrophil activation and formation of neutrophil extracellular traps (NETs). Plasma from severely septic humans also induced TLR4-dependent platelet-neutrophil interactions, leading to the production of NETs. The NETs retained their integrity under flow conditions and ensnared bacteria within the vasculature. The entire event occurred primarily in the liver sinusoids and pulmonary capillaries, where NETs have the greatest capacity for bacterial trapping. We propose that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis.
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              Extracorporeal Life Support Organization Registry International Report 2016.

              Data on extracorporeal life support (ECLS) use and survival submitted to the Extracorporeal Life Support Organization's data registry from the inception of the registry in 1989 through July 1, 2016, are summarized in this report. The registry contained information on 78,397 ECLS patients with 58% survival to hospital discharge. Extracorporeal life support use and centers providing ECLS have increased worldwide. Extracorporeal life support use in the support of adults with respiratory and cardiac failure represented the largest growth in the recent time period. Extracorporeal life support indications are expanding, and it is increasingly being used to support cardiopulmonary resuscitation in children and adults. Adverse events during the course of ECLS are common and underscore the need for skilled ECLS management and appropriately trained ECLS personnel and teams.
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                Author and article information

                Contributors
                patrick.siegel@universitaets-herzzentrum.de
                Journal
                J Thromb Thrombolysis
                J Thromb Thrombolysis
                Journal of Thrombosis and Thrombolysis
                Springer US (New York )
                0929-5305
                1573-742X
                16 September 2021
                16 September 2021
                : 1-10
                Affiliations
                [1 ]GRID grid.5963.9, Department of Cardiology and Angiology I, , University Heart Center Freiburg – Bad Krozingen, Faculty of Medicine, University of Freiburg, ; Freiburg, Germany
                [2 ]GRID grid.5963.9, Department of Cardiovascular Surgery, , University Heart Center Freiburg – Bad Krozingen, Faculty of Medicine, University of Freiburg, ; Freiburg, Germany
                Author information
                http://orcid.org/0000-0002-6976-8961
                Article
                2562
                10.1007/s11239-021-02562-9
                8444511
                34529213
                d933c80b-1c78-4082-bdf8-8b5294af51c5
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 August 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002714, albert-ludwigs-universität freiburg;
                Award ID: albert-ludwigs-universität freiburg
                Award Recipient :
                Funded by: Albert-Ludwigs-Universität Freiburg im Breisgau (1016)
                Categories
                Article

                Hematology
                extracorporeal membrane oxygenation,mortality,platelets,hemorrhage,critical care
                Hematology
                extracorporeal membrane oxygenation, mortality, platelets, hemorrhage, critical care

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