Prevention and Treatment of Venous Thromboembolism Associated with Coronavirus Disease 2019 Infection: A Consensus Statement before Guidelines

Author(s): Zhenguo Zhai ¹ ^, ² ^, ³ ^, ^* , Chenghong Li ⁴ ^, ^* , Yaolong Chen ⁵ ^, ^* , Grigorios Gerotziafas ⁶ , Zhenlu Zhang ⁷ , Jun Wan ¹ ^, ² ^, ³ , Peng Liu ⁸ , Ismaïl Elalamy ⁶ ^, ⁹ ^, ^* , Chen Wang ¹ ^, ² ^, ³ ^, ¹⁰ , On behalf of the Prevention Treatment of VTE Associated with COVID-19 Infection Consensus Statement Group Pulmonary Embolism Pulmonary Vascular Diseases Group of the Chinese Thoracic Society Pulmonary Embolism Pulmonary Vascular Disease Working Committee of Chinese Association of Chest Physicians National Cooperation Group on Prevention Treatment of Pulmonary Embolism Pulmonary Vascular Disease National Program Office for Prevention Treatment of Pulmonary Embolism Deep Vein Thrombosis China Grade Center Evidence-based Medicine Center of School of Basic Medical Sciences of Lanzhou University

Publication date (Electronic): 21 April 2020

Journal: Thrombosis and Haemostasis

Publisher: Georg Thieme Verlag KG

Keywords: COVID-19, venous thromboembolism, coagulation abnormalities, prophylaxis, consensus

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Abstract

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected. Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases. Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders. Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19. This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed. With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions.

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Most cited references 27

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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

Fei Zhou, Ting Yu, Ronghui Du … (2020)

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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Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Nanshan Chen, Min Zhou, Xuan Dong … (2022)

Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.

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Author and article information

Journal

Journal ID (nlm-ta): Thromb Haemost

Journal ID (iso-abbrev): Thromb. Haemost

Journal ID (doi): 10.1055/s-00035024

Title: Thrombosis and Haemostasis

Publisher: Georg Thieme Verlag KG (Stuttgart · New York )

ISSN (Print): 0340-6245

ISSN (Electronic): 2567-689X

Publication date (Print): June 2020

Publication date (Electronic): 21 April 2020

Volume: 120

Issue: 6

Pages: 937-948

Affiliations

[1 ]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China

[2 ]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China

[3 ]National Clinical Research Center for Respiratory Diseases, Beijing, China

[4 ]Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Jianghan University, Wuhan, China

[5 ]Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China

[6 ]Hematology and Thrombosis Center, Tenon University Hospital, INSERM UMRS 938, Sorbonne University, Paris, France

[7 ]Department of Clinical Laboratory, Wuhan Asia Heart Hospital, Wuhan, China

[8 ]Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China

[9 ]Department of Obstetrics and Gynaecology, the First I.M. Sechenov Moscow State Medical University, Moscow, Russia

[10 ]Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Author notes

Address for correspondence Chen Wang, MD, PhD Department of Pulmonary and Critical Care Medicine China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. No. 2 East Yinghua Road, Chaoyang District, Beijing 100029China cyh-birm@ 123456263.net zhaizhenguo2011@ 123456126.com

Ismaïl Elalamy, MD, PhD Hematology and Thrombosis Center, Tenon University Hospital INSERM UMRS 938, Sorbonne University, ParisFrance ismail.elalamy@ 123456aphp.fr

Article

Publisher ID: 200195

DOI: 10.1055/s-0040-1710019

PMC ID: 7295267

PubMed ID: 32316065

SO-VID: ab501af8-925b-41b2-a5d8-b34e2f9edc5b

License:

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

History

Date received : 02 April 2020

Date accepted : 06 April 2020

Funding

Funded by: Chinese Academy of Engineering emergency research and cultivation project for COVID-19

Award ID: 2020-KYGG-01–05

Funded by: National Key Research and Development Program of China

Award ID: 2016YFC0905600

Funded by: National Key Research and Development Program of China

Award ID: 2016YFC0901104

Funded by: CAMS Innovation Fund for Medical Sciences

Award ID: 2018-I2M-1–003

Funded by: National Natural Science Foundation of China

Award ID: 81570049

Funded by: National Natural Science Foundation of China

Award ID: 81970058

Funding This guideline is funded by the Chinese Academy of Engineering emergency research and cultivation project for COVID-19 (grant number: 2020-KYGG-01–05), National Key Research and Development Program of China (grant numbers: 2016YFC0905600 and 2016YFC0901104), CAMS Innovation Fund for Medical Sciences (grant number: 2018-I2M-1–003), and National Natural Science Foundation of China (grant numbers: 81570049 and 81970058).