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      Thromboembolic risk and anticoagulant therapy in COVID‐19 patients: emerging evidence and call for action

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          Summary

          Emerging evidence shows that severe coronavirus disease 2019 (COVID‐19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID‐19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D‐dimer might help in early recognition of these high‐risk patients and also predict outcome. Preliminary data show that in patients with severe COVID‐19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis‐induced coagulopathy criteria or with markedly elevated d‐dimer. Recent recommendations suggest that all hospitalized COVID‐19 patients should receive thromboprophylaxis, or full therapeutic‐intensity anticoagulation if such an indication is present.

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Fei Zhou, Ting Yu, Ronghui Du … (2020)
          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

            Ning Tang, Dengju Li, Xiong Wang … (2020)
            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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              Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

              Ning Tang, Huan Bai, Xing Chen … (2020)
              Background A relatively high mortality of severe coronavirus disease 2019 (COVID‐19) is worrying, and the application of heparin in COVID‐19 has been recommended by some expert consensus because of the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. Methods Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID‐19 in Tongji hospital were retrospectively analyzed. The 28‐day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis‐induced coagulopathy (SIC) score or D‐dimer result. Results There were 449 patients with severe COVID‐19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D‐dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference in 28‐day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P  = .910). But the 28‐day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P  = .029), or D‐dimer >6‐fold of upper limit of normal (32.8% vs 52.4%, P  = .017). Conclusions Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID‐19 patients meeting SIC criteria or with markedly elevated D‐dimer.
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                Author and article information

                Contributors
                Anastasios Kollias:
                ORCID: https://orcid.org/0000-0002-2098-1665
                taskollias@gmail.com
                Journal
                Journal ID (nlm-ta): Br J Haematol
                Journal ID (iso-abbrev): Br. J. Haematol
                Journal ID (doi): 10.1111/(ISSN)1365-2141
                Journal ID (publisher-id): BJH
                Title: British Journal of Haematology
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0007-1048
                ISSN (Electronic): 1365-2141
                Publication date (Electronic): 04 May 2020
                Electronic Location Identifier: 10.1111/bjh.16727
                Affiliations
                [ 1 ] Third Department of Medicine National and Kapodistrian University of Athens School of Medicine Sotiria Hospital Athens Greece
                Author notes
                [*] [* ] Correspondence: Anastasios Kollias, Third Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Sotiria Hospital, 152 Mesogion Avenue, Athens 11527, Greece.

                E‐mail: taskollias@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-2098-1665
                Article
                Publisher ID: BJH16727
                DOI: 10.1111/bjh.16727
                PMC ID: 7264537
                PubMed ID: 32304577
                SO-VID: 65f9e411-2070-4d13-aa20-3c5315f6e519
                Copyright © © 2020 British Society for Haematology and John Wiley & Sons Ltd
                License:

                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.

                History
                Date received : 13 April 2020
                Date accepted : 16 April 2020
                Page count
                Figures: 0, Tables: 1, Pages: 3, Words: 2612
                Categories
                Subject: Commentary
                Subject: Commentary
                Custom metadata
                source-schema-version-number 2.0
                edited-state corrected-proof
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:02.06.2020

                ScienceOpen disciplines: Hematology
                Keywords: anticoagulant,prophylaxis,sars‐cov‐2,thromboembolism,thrombosis
                Data availability:
                ScienceOpen disciplines: Hematology
                Keywords: anticoagulant, prophylaxis, sars‐cov‐2, thromboembolism, thrombosis

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