English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Since December 2019, a newly identified coronavirus disease (COVID-19) has spread in China and the rest of World. The pathogen has been identified as a novel enveloped RNA betacoronavirus [1], with a phylogenetic similarity to SARS-CoV named severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). The World Health Organization (WHO) has recently declared COVID-19 a public health emergency of international concern [2]. At the time of writing, the COVID-19 epidemic is still ongoing. Latest numbers estimate > 1,614,405 people infected worldwide, with 1,155,207 active cases (49,115 critical cases, 4%) and 96,789 deaths [3]. In Italy, 143,626 infected people (8.9% of all infected people worldwide), 18,279 death people, 96,877 active cases with 3.7% of critical cases have been reported to date [4]. The clinical feature of disease is very wide and ranges from minor unspecified symptoms (such as fever, dry cough and diarrhea) to severe pneumonia, lung insufficiency and death. Fall in respiratory insufficiency needing mechanical ventilation, or in multiple organ failure occurs in 5% of the infected patients, mainly according to age and comorbidities [5]. Disease severity also correlates with pro-inflammatory cytokines (i.e. interleukin (IL-2), IL-6, IL-7, IL-10, granulocyte colony-stimulating factor (G-CSF), interferon γ-induced protein (IP)-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1A and tumor necrosis factor (TNF)-α), although it is not yet clear what is the cause of such a cytokine storm [6]. Among the several clinical and biochemical parameters associated with poor prognosis, increased D-dimer levels have gained particular attention and represent a predictor of the development of acute respiratory distress syndrome (ARDS). Tang et al [7] described the outcome of 183 patients admitted to the Tongji Hospital in Wuhan with RNA detection confirmed 2019-nCoV pneumonia. The authors observed that disseminated intravascular coagulation (DIC) is a frequent occurrence in worsening of COVID-19 pneumonia. Coagulation abnormalities and marked increase of D-dimer were often associated with increased mortality or concomitant severe thromboembolic complications. Surprisingly, the authors noted that in the Chinese population, the prevalence of thromboembolic events was particularly elevated among patients with severe lung failure. Similar prevalence was observed by Cui et al in 81 patients admitted to intensive care units (ICUs), where the prevalence of major thromboembolism was around 25% [8]. Low molecular weight heparin (LMWH) or unfractionated heparin (UFH) at prophylactic doses are associated with a reduced 28-day mortality in more severe COVID-19 patients [9], displaying a sepsis-induced coagulopathy (SIC) score ≥ 4 (40.0% vs. 64.2%, P = 0.029) or D-dimer levels more than six-fold the upper limit of normal (32.8% vs. 52.4%, P = 0.017). Comparably, but slightly higher records of thromboembolic complications (up to about 30%) were observed in Italian patients admitted in ICU (unpublished data). These numbers will be smaller but not less than 2% in all Italian COVID-19 patients hospitalized. Normal incidence of deep vein thrombosis in hospitalized Italian patients without COVID-19 is reported 0.025% [10]. One of the possible reasons for the increased frequency of thromboembolic complications in Italian patients could be attributed to higher median age of 45.5 [4] compared to China at 37.4 [5]. The thromboembolic complications observed in Italian patients affected by severe COVID-19 include venous thromboembolism and pulmonary embolism (VTE). All thromboembolic complications are documented by compressive ultrasonography (CUS) or computerized axial tomography (CT) scan. All patients share alterations of hemostatic parameters showing: 1) elevated levels of D-dimer (> 1,000 at admission rapidly rising); 2) elevated fibrinogen which may be consumed in the late stage of disease; 3) thrombocytopenia, but less commonly than in classical DIC; and 4) normal or somewhat prolonged partial prothrombin time (PTT) and international normalized ratio (INR). Additional coagulation tests have shown elevated levels of von Willebrand factor and factor VIII, and normal levels of natural anticoagulants such protein C, protein S and antithrombin III (unpublished data). Table 1 shows the most frequent hemostatic alterations observed among Italian patients admitted to ICU for respiratory failure. COVID-19 produces a sort of DIC which is usually characterized by hypercoagulability. The exact pathogenetic mechanism of COVID-19-related DIC is unclear, although inflammatory drive and cytokine release may be responsible for the Manuscript submitted April 15, 2020, accepted April 17, 2020

Abnormal Hemostatic Parameters and Risk of Thromboembolism Among Patients With COVID-19 Infection