This single-centre, retrospective, observational study was done at Anesthesia and Intensive Care Unit (ICU), Santa Maria Annunziata Hospital (Bagno a Ripoli, Tuscany, Italy), which is one of the designated hospitals to the Tuscany Region to treat patients with COVID-19 pneumonia. Forty consecutive adult patients (≥18 years old) with severe COVID-19 admitted to ICU between February 28, 2020 (i.e, when the first patient was admitted), and 10 April 2020, were retrospectively enrolled.
The diagnosis of severe COVID-19 pneumonia was according to World Health Organization (WHO)  interim guidance and it was confirmed by RNA detection of the SARS-CoV-2 in clinical laboratory of Santa Maria Annunziata Hospital (Bagno a Ripoli, Italy).
The Ethics Commission of Area Vasta Centro (Tuscany, Italy) approved this retrospective study. Written informed consent was waived due to the emergence of this infectious disease in Italy.
Demographic and clinical information were collected, including age, gender, body mass index (BMI), preexisting illness (diabetes, hypertension, cardiovascular disease, chronic obstructive pulmonary disease), onset of symptom to hospital admission and to ICU admission, Sequential Organ Failure Assessment (SOFA) on ICU admission, PaO2/FiO2 on ICU admission, need to non-invasive ventilation or mechanical ventilation, total length of ICU and hospital stay, and ICU and hospital mortality. The Sepsis Induced coagulopathy (SIC) score system including PT, platelet count and SOFA was calculated and a SIC criteria total score ≥4 was considered, as suggested by International Society of Thrombosis and Haemostasis (ISTH) .
At the time of admission (T0) and 5 (T5) and 10 (T10) days later, peripheral venous blood sample was taken and routine blood examinations with hemoglobin level, platelets count, coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels, d-dimer, antithrombin III, interleukin-6 (IL-6), procalcitonin, were collected. An additional venous blood sample was placed into citrate-containing tubes (BD Vacutainer®; BD Plymouth, UK) and analyzed by rotational thromboelastometry (ROTEM® gamma; Tem Innovations GmbH, Munich, Germany) according to the manufacturer’s recommendations. Extrinsic and intrinsic coagulation cascades were evaluated by using the EXTEM and INTEM tests, respectively. The influence of fibrinogen on clot firmness was estimated by using the platelet inactivating FIBTEM test. The following ROTEM® parameters were analyzed: 1) clotting time (CT, s), time from the beginning of the coagulation analysis until an increase in amplitude of thromboelastogram of 2 mm; 2) clot formation time (CFT, s), time between an increase in amplitude of thromboelastogram from 2 to 20 mm; 3) A5 and A10, clot strength at 5 and 10 minutes, 4) maximum clot firmness (MCF, mm) or the maximum amplitude (mm) reached in the thromboelastogram and 5) maximum lysis (ML,%), measure of fibrinolysis.
All patients received antiviral and appropriate supportive therapies on the day of the admission and throughout the hospital stay.
Thromboprophylaxis with low molecular weight heparin (LMWH, 40-60 mg enoxaparin/day) was used in according to guidelines of Surviving Sepsis Campaign 2016 .
Bilateral extended compression ultrasound (ECUS) from common femoral vein through the popliteal vein up to the calf veins confluence was performed in each of the included patients on day of admission and five days after, using GE Logiq-e1 Vision scanner (GE, Healthcare, Italy). Moreover, at the same time, ultrasound screening was helpful for detecting catheter-related thrombosis.
The results were expressed as mean ± standard deviation or number (percentage), wherever appropriate. Normally distributed data were compared by Student’s t-tests. Categorical variables were compared using the chi-squared test. A p value of < 0.05 was considered statistically significant. SPSS software version 25.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.