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      Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis

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          Abstract

          Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9–29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6–61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8–34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8–5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.

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          The online version of this article (10.1007/s00134-020-06031-4) contains supplementary material, which is available to authorized users.

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          Most cited references51

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          Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung.

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            Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis.

            Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially devastating complication of anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Our objective was to determine and compare the incidences of HIT in surgical and medical patients receiving thromboprophylaxis with either UFH or LMWH. All relevant studies identified in the MEDLINE database (1984-2004), not limited by language, and from reference lists of key articles were evaluated. Randomized and nonrandomized controlled trials comparing prophylaxis with UFH and LMWH and measuring HIT or thrombocytopenia as outcomes were included. Two reviewers independently extracted data on thromboprophylaxis (type, dose, frequency, and duration), definition of thrombocytopenia, HIT assay, and rates of the following outcomes: HIT, thrombocytopenia, and thromboembolic events. HIT was defined as a decrease in platelets to less than 50% or to less than 100 x 10(9)/L and positive laboratory HIT assay. Fifteen studies (7287 patients) were eligible: 2 randomized controlled trials (RCTs) measuring HIT (1014 patients), 3 prospective studies (1464 patients) with nonrandomized comparison groups in which HIT was appropriately measured in both groups, and 10 RCTs (4809 patients) measuring thrombocytopenia but not HIT. Three analyses were performed using a random effects model and favored the use of LMWH: (1) RCTs measuring HIT showed an odds ratio (OR) of 0.10 (95% confidence interval [CI], 0.01-0.2; P = .03); (2) prospective studies measuring HIT showed an OR of 0.10 (95% CI, 0.03-0.33; P < .001); (3) all 15 studies measured thrombocytopenia. The OR was 0.47 (95% CI, 0.22-1.02; P = .06). The inverse variance-weighted average that determined the absolute risk for HIT with LMWH was 0.2%, and with UFH the risk was 2.6%. Most studies were of patients after orthopedic surgery.
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              Meta-analysis, funnel plots and sensitivity analysis.

              Publication bias is a major problem, perhaps the major problem, in meta-analysis (or systematic reviews). Small studies are more likely to be published if their results are 'significant' than if their results are negative or inconclusive, and so the studies available for review are biased in favour of those with positive outcomes. Correcting for this bias is not possible without making untestable assumptions. In this paper, a sensitivity analysis is suggested which is based on fitting a model to the funnel plot. Some examples are discussed.
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                Author and article information

                Contributors
                fede.j@hotmail.it
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                23 April 2020
                23 April 2020
                2020
                : 46
                : 6
                : 1154-1169
                Affiliations
                [1 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Cardio-Thoracic Surgery Department, Heart and Vascular Centre, Cardiovascular Research Institute Maastricht (CARIM), , Maastricht University Medical Centre (MUMC), ; P. Debeylaan, 26, 6220 AZ Maastricht, The Netherlands
                [2 ]GRID grid.411489.1, ISNI 0000 0001 2168 2547, Cardiac Surgery Unit, Department of Experimental and Clinical Medicine, , University “Magna Graecia” of Catanzaro, ; Catanzaro, Italy
                [3 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), , Maastricht University Medical Center, ; Maastricht, The Netherlands
                [4 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, IRCCS San Donato, , University of Milan, ; Milan, Italy
                [5 ]GRID grid.18147.3b, ISNI 0000000121724807, Department of Cardiac Surgery, Circolo Hospital, , University of Insubria, ; Varese, Italy
                Article
                6031
                10.1007/s00134-020-06031-4
                7292815
                32328725
                cd0e41fa-6414-467e-8b05-a048d4165015
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial 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-nc/4.0/.

                History
                : 20 November 2019
                : 28 March 2020
                Categories
                Systematic Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Emergency medicine & Trauma
                platelets,extracorporeal membrane oxygenation,platelet dysfunction,platelet activation,bleeding

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