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      High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019

      research-article
      , MD 1 , , , MD 1 , , MD 1 , , MD, PhD 2 , , MD 2 , , MD 2 , , MD 2 , , MD 4 , , MD 4 , , MD 3 , , MD 3 , , MD 3 , , MD 3 , , MD 5 , , MD 5 , , MD 1 , , MD 1 , , MD, PhD 1 , , MD 6 , , MD 6 , , PhD 6
      Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
      John Wiley and Sons Inc.
      coronavirus disease 2019, thrombophilia, thrombosis, Clinical Studies, Vascular Biology

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          Abstract

          Background

          Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID‐19) infection. This characteristic is unusual and seems specific to COVID‐19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID‐19 infections.

          Methods and Results

          In 89 consecutive patients hospitalized for COVID‐19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D‐dimer, fibrinogen, or CRP (C‐reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality.

          Conclusions

          We assess a high prevalence of positive tests detecting thrombophilia in COVID‐19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID‐19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID‐19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition.

          Registration

          URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.

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          Most cited references24

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

          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

            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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              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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                Author and article information

                Contributors
                ferrari.e@chu-nice.fr
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                26 October 2020
                03 November 2020
                : 9
                : 21 ( doiID: 10.1002/jah3.v9.21 )
                : e017773
                Affiliations
                [ 1 ] Department of Cardiology University Hospital of Nice France
                [ 2 ] Department of Emergency University Hospital of Nice France
                [ 3 ] Department of Infectious Diseases University Hospital of Nice France
                [ 4 ] Department of Intensive Care 1 University Hospital of Nice France
                [ 5 ] Department of Intensive Care 2 University Hospital of Nice France
                [ 6 ] Hematology Laboratory University Hospital of Nice France
                Author notes
                [*] [* ]Correspondence to: Emile Ferrari, MD, Cardiology Department, Pasteur Hospital, Nice, France. E‐mail: ferrari.e@ 123456chu-nice.fr
                Author information
                https://orcid.org/0000-0002-8233-6039
                https://orcid.org/0000-0002-7186-2818
                https://orcid.org/0000-0001-6436-3642
                https://orcid.org/0000-0001-9715-197X
                https://orcid.org/0000-0002-0741-1609
                Article
                JAH35620
                10.1161/JAHA.120.017773
                7763401
                32972320
                212f6517-f465-42a9-8c7f-90322bc01730
                © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Page count
                Figures: 0, Tables: 3, Pages: 6, Words: 4185
                Categories
                Original Research
                Original Research
                Vascular Medicine
                Custom metadata
                2.0
                03 November 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:03.11.2020

                Cardiovascular Medicine
                coronavirus disease 2019,thrombophilia,thrombosis,clinical studies,vascular biology

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