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      Subcutaneous Enoxaparin Safely Facilitates Bedside Sustained Low-Efficiency Hemodialysis in Hypercoagulopathic Coronavirus Disease 2019 Patients—A Proof-of-Principle Trial

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          Abstract

          Objectives:

          Renal replacement therapy in coronavirus disease 2019 patients is complicated by increased activation of the coagulation system. This may worsen the quality of hemodialysis and contribute to a shortage of dialysis machines as well as plastic disposables during the pandemic. This study describes a simple and safe protocol of anticoagulation with low-molecular-weight heparin in combination with bedside sustained low-efficiency hemodialysis in coronavirus disease 2019 patients.

          Design:

          Monocentric observational cross-over trial investigating sustained low-efficiency hemodialysis with unfractionated heparin following sustained low-efficiency hemodialysis with low-molecular-weight heparin.

          Setting:

          Coronavirus disease 2019-ICU in a German Tertiary Care University Hospital.

          Patients:

          Three consecutive severe coronavirus disease 2019 patients receiving nine sustained low-efficiency hemodialysis therapies with unfractionated heparin followed by 18 sustained low-efficiency hemodialysis therapies with low-molecular-weight heparin.

          Interventions:

          Switch from IV unfractionated heparin to subcutaneous low-molecular-weight heparin enoxaparin in therapeutic doses for patients receiving bedside sustained low-efficiency hemodialysis.

          Measurements and Main Results:

          Nine renal replacement therapy sessions in patients anticoagulated with high doses of unfractionated heparin had to be discontinuated prematurely because of clotting of tubes or membrane and poor quality of hemodialysis. In the same patients, the switch to anticoagulation with therapeutic doses of the low-molecular-weight heparin enoxaparin allowed undisturbed bedside sustained low-efficiency hemodialysis for at least 12 hours. Quality of hemodialysis was excellent, no bleeding event was observed.

          Conclusions:

          Systemic anticoagulation with subcutaneous enoxaparin provides an effective and safe renal replacement procedure in critically ill patients with coronavirus disease 2019 and hypercoagulability. The protocol reduces the risk of filter clotting, blood loss, and poor dialysis quality and may also prevent systemic thromboembolism.

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          Most cited references8

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          Incidence of thrombotic complications in critically ill ICU patients with COVID-19

          Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
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            Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

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              Thromboinflammation and the hypercoagulability of COVID‐19

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                Author and article information

                Journal
                Crit Care Explor
                Crit Care Explor
                CC9
                Critical Care Explorations
                Wolters Kluwer Health
                2639-8028
                June 2020
                15 June 2020
                : 2
                : 6
                : e0155
                Affiliations
                [1 ]Renal Devision Department of Medicine, University Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Strasse, Freiburg, Germany.
                [2 ]Department of Anesthesiology and Intensive Care Medicine, University Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Strasse, Freiburg, Germany.
                Author notes
                For information regarding this article, E-mail: Johannes.kalbhenn@ 123456uniklinik-freiburg.de
                Article
                00019
                10.1097/CCE.0000000000000155
                7314355
                dbff60fd-4200-4c52-8750-473bfa45c4b7
                Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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                Brief Report
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                acute kidney injury,anticoagulation,coronavirus disease 2019,enoxaparin,hemodialysis,heparin,renal replacement therapy

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