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      Tissue plasminogen activator (tPA) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): A case series

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          Abstract

          A prothrombotic coagulopathy is commonly found in critically ill COVID‐19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID‐19 respiratory failure is a relatively preserved lung compliance and high Alveolar‐arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low‐compliance in ARDS. The COVID‐19 pandemic is overwhelming the world’s medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID‐19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.

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          Most cited references11

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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            Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

            Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
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              Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

              Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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                Author and article information

                Contributors
                hunter.moore@ucdenver.edu
                cdbarret@mit.edu
                Journal
                J Thromb Haemost
                J. Thromb. Haemost
                10.1111/(ISSN)1538-7836
                JTH
                Journal of Thrombosis and Haemostasis
                John Wiley and Sons Inc. (Hoboken )
                1538-7933
                1538-7836
                11 May 2020
                Affiliations
                [ 1 ] Feinstein Institutes for Medical Research Northwell Health Manhasset NY USA
                [ 2 ] Department of Surgery Ernest E Moore Shock Trauma Center at Denver Health Denver CO USA
                [ 3 ] Department of Surgery University of Colorado Denver Aurora CO USA
                [ 4 ] Department of Medicine University of Colorado Denver Aurora CO USA
                [ 5 ] Department of Pediatrics, Pulmonary Medicine University of Colorado Denver Aurora CO USA
                [ 6 ] Center for Precision Cancer Medicine Departments of Biological Engineering and Biology Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA USA
                [ 7 ] Division of Acute Care Surgery, Trauma and Surgical Critical Care Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA
                Author notes
                [*] [* ] Correspondence

                Hunter B. Moore, Department of Surgery, University of Colorado Denver, 12631 E 17th Ave #6117, Aurora, CO 80045, USA

                Email: hunter.moore@ 123456ucdenver.edu

                Christopher D. Barrett, Division of Acute Care Surgery, Trauma and Surgical Critical Care, Department of Surgery, Beth Israel Deaconess Medical Center, 110 Francis Street, Suite 9B, Boston, MA 02215, USA

                Email: cdbarret@ 123456mit.edu

                Article
                JTH14828
                10.1111/jth.14828
                7262152
                32267998
                b82d9d5a-e7bd-432e-907f-c7bab1593f9b
                © 2020 International Society on Thrombosis and Haemostasis

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                Page count
                Figures: 0, Tables: 0, Pages: 4, Words: 4131
                Product
                Categories
                Case Report
                Case Reports
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:01.06.2020

                Hematology
                acute respiratory distress syndrome (ards),case report,covid‐19,fibrinolysis,tissue plasminogen activator (tpa)

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