Coagulopathy, Venous Thromboembolism, and Anticoagulation in Patients with COVID-19
TL;DR: Clinicians can use a list of clinical considerations that clinicians can use for the prevention and treatment of VTE in patients with COVID‐19, along with practical issues of anticoagulant selection and duration.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic, and patients with the infection are referred to as having COVID-19. Although COVID-19 is commonly considered a respiratory disease, there is clearly a thrombotic potential that was not expected. The pathophysiology of the disease and subsequent coagulopathy produce an inflammatory, hypercoagulable, and hypofibrinolytic state. Several observational studies have demonstrated surprisingly high rates of venous thromboembolism (VTE) in both general ward and intensive care patients with COVID-19. Many of these observational studies demonstrate high rates of VTE despite patients being on standard, or even higher intensity, pharmacologic VTE prophylaxis. Fibrinolytic therapy has also been used in patients with acute respiratory distress syndrome. Unfortunately, high quality randomized controlled trials are lacking. A literature search was performed to provide the most up-to-date information on the pathophysiology, coagulopathy, risk of VTE, and prevention and treatment of VTE in patients with COVID-19. These topics are reviewed in detail, along with practical issues of anticoagulant selection and duration. Although many international organizations have produced guidelines or consensus statements, they do not all cover the same issues regarding anticoagulant therapy for patients with COVID-19, and they do not all agree. These statements and the most recent literature are combined into a list of clinical considerations that clinicians can use for the prevention and treatment of VTE in patients with COVID-19.
Citations
More filters
01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: 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 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.
4,408 citations
TL;DR: An overview of the management of patients with COPD during the COVID-19 pandemic is presented and inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should be used as indicated for stable COPD management.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required. It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic. It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2. During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering. Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome. Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols. Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.
345 citations
TL;DR: In this paper, the authors investigated the risk of ICU bloodstream infection (BSI) in critically ill COVID-19 patients compared to non-COVID19 patients in a matched case-cohort study.
Abstract: The primary objective of this study was to investigate the risk of ICU bloodstream infection (BSI) in critically ill COVID-19 patients compared to non-COVID-19 patients. Subsequently, we performed secondary analyses in order to explain the observed results. We conducted a matched case-cohort study, based on prospectively collected data from a large ICU cohort in France. Critically ill COVID-19 patients were matched with similar non-COVID-19 patients. ICU-BSI was defined by an infection onset occurring > 48 h after ICU admission. We estimated the effect of COVID-19 on the probability to develop an ICU-BSI using proportional subdistribution hazards models. We identified 321 COVID-19 patients and 1029 eligible controls in 6 ICUs. Finally, 235 COVID-19 patients were matched with 235 non-COVID-19 patients. We observed 43 ICU-BSIs, 35 (14.9%) in the COVID-19 group and 8 (3.4%) in the non-COVID-19 group (p ≤ 0.0001), respectively. ICU-BSIs of COVID-19 patients were more frequently of unknown source (47.4%). COVID-19 patients had an increased probability to develop ICU-BSI, especially after 7 days of ICU admission. Using proportional subdistribution hazards models, COVID-19 increased the daily risk to develop ICU-BSI (sHR 4.50, 95% CI 1.82–11.16, p = 0.0012). Among COVID-19 patients (n = 235), a significantly increased risk for ICU-BSI was detected in patients who received tocilizumab or anakinra (sHR 3.20, 95% CI 1.31–7.81, p = 0.011) but not corticosteroids. Using prospectively collected multicentric data, we showed that the ICU-BSI risk was higher for COVID-19 than non-COVID-19 critically ill patients after seven days of ICU stay. Clinicians should be particularly careful on late ICU-BSIs in COVID-19 patients. Tocilizumab or anakinra may increase the ICU-BSI risk.
99 citations
TL;DR: Lessons from the Placid Trial as mentioned in this paper ) is a good starting point for our work. But it is not suitable for outdoor sports, and it cannot be used for all sports.
Abstract: Lessons from the Placid Trial
40 citations
TL;DR: In this paper, the role of neutrophil extracellular traps (NETs) in lung injury and multi-organ damage in COVID-19 disease has been investigated.
Abstract: Neutrophil extracellular traps (NETs), built from mitochondrial or nuclear DNA, proteinases, and histones, entrap and eliminate pathogens in the course of bacterial or viral infections. Neutrophils' activation and the formation of NETs have been described as major risk factors for acute lung injury, multi-organ damage, and mortality in COVID-19 disease. NETs-related lung injury involves both epithelial and endothelial cells, as well as the alveolar-capillary barrier. The markers for NETs formation, such as circulating DNA, neutrophil elastase (NE) activity, or myeloperoxidase-DNA complexes, were found in lung specimens of COVID-19 victims, as well as in sera and tracheal aspirates obtained from COVID-19 patients. DNA threads form large conglomerates causing local obstruction of the small bronchi and together with NE are responsible for overproduction of mucin by epithelial cells. Various components of NETs are involved in the pathogenesis of cytokine storm in SARS-CoV-2 pulmonary disease. NETs are responsible for the interplay between inflammation and thrombosis in the affected lungs. The immunothrombosis, stimulated by NETs, has a poor prognostic significance. Better understanding of the role of NETs in the course of COVID-19 can help to develop novel approaches to the therapeutic interventions in this condition.
34 citations
References
More filters
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
TL;DR: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness, and patients often presented without fever, and many did not have abnormal radiologic findings.
Abstract: Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of...
22,622 citations
"Coagulopathy, Venous Thromboembolis..." refers background in this paper
...virus has caused more overall deaths due to its rapid person-to-person transmission and potentially mild initial infection presentation.(7) Similar to these prior outbreaks, SARS-CoV-2 has been associated with a higher incidence of thrombotic events than would be expected in hospitalized infected or critically ill patients....
[...]
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
20,189 citations
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
16,635 citations
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
16,282 citations
"Coagulopathy, Venous Thromboembolis..." refers background in this paper
...58 One study in China reported that IL-6 was elevated in 52%, ferritin in 63%, erythrocyte sedimentation rate in 85%, and C-reactive protein (CRP) in 86% of patients.(20) These numbers are even higher in sicker patients (Table 2)....
[...]