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      Increasing dosages of low-molecular-weight heparin in hospitalized patients with Covid-19

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          Abstract

          We conducted an observational cohort study in adult patients consecutively admitted for the respiratory illness Covid-19 to our hub hospital from March 9 to April 7, 2020. The high observed rate of venous thromboembolism prompted us to increase the prophylactic doses of enoxaparin from 40 mg daily up to 1 mg/kg twice daily in patients admitted to intensive care units (ICU), 0.7 mg/kg twice daily in high-intensity of care wards and 1 mg/kg daily in low-intensity of care wards. Patients on high enoxaparin doses were compared to those who received prophylaxis with the standard dosage. Efficacy endpoints were mortality, clinical deterioration, and the occurrence of venous thromboembolism, safety endpoint was the occurrence of major bleeding. Of 278 patients with Covid-19, 127 received prophylaxis with high enoxaparin doses and 151 with standard dosage. At 21 days, the incidence rate of death and clinical deterioration were lower in patients on higher doses than in those on the standard dosage (hazard ratio 0.39, 95% confidence interval 0.23–0.62), and the incidence of venous thromboembolism was also lower (hazard ratio 0.52, 95% confidence interval 0.26–1.05). Major bleeding occurred in four of 127 patients (3.1%) on the high enoxaparin dosage. In conclusion, in the cohort of patients with Covid-19 treated with high enoxaparin dosages we observed a 60% reduction of mortality and clinical deterioration and a 50% reduction of venous thromboembolism compared to standard dosage prophylaxis. However, 3% of patients on high enoxaparin dosages had non-fatal major bleeding.

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          The online version contains supplementary material available at 10.1007/s11739-020-02585-9.

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          Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

          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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            High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

            Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.
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              Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

              Background: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. Design: Prospective cohort study. Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. Patients: The first 12 consecutive COVID-19–positive deaths. Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. Limitation: Limited sample size. Conclusion: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. Primary Funding Source: University Medical Center Hamburg-Eppendorf.
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                Author and article information

                Contributors
                ida.martinelli@policlinico.mi.it
                Journal
                Intern Emerg Med
                Intern Emerg Med
                Internal and Emergency Medicine
                Springer International Publishing (Cham )
                1828-0447
                1970-9366
                3 January 2021
                : 1-7
                Affiliations
                [1 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, A. Bianchi Bonomi Hemophilia and Thrombosis Center, , Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, ; Via Pace 9, 20122 Milan, Italy
                [2 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Respiratory Unit and Cystic Fibrosis Adult Center, , Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, ; Milan, Italy
                [3 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Pathophysiology and Transplantation, , University of Milan, ; Milan, Italy
                [4 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Department of Medicine—Acute Medical Unit, , Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, ; Milan, Italy
                [5 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Department of Anesthesia, Intensive Care and Emergency, , Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, ; Milan, Italy
                [6 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Department of Internal Medicine, Infectious Diseases Unit, , Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, ; Milan, Italy
                [7 ]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Radiology Unit, , Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, ; Milan, Italy
                Article
                2585
                10.1007/s11739-020-02585-9
                7778858
                33389568
                8f8d38cf-68bd-47ae-b3d1-d2a573ce418f
                © Società Italiana di Medicina Interna (SIMI) 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 28 August 2020
                : 21 November 2020
                Categories
                Im - Original

                Emergency medicine & Trauma
                anticoagulants,coronavirus,enoxaparin,mortality,venous thromboembolism
                Emergency medicine & Trauma
                anticoagulants, coronavirus, enoxaparin, mortality, venous thromboembolism

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