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DOI: 10.1055/s-0040-1710337
Coronavirus Disease 2019, Prothrombotic Factors, and Venous Thromboembolism
Coronavirus disease 2019 (COVID-19) is causing devastating morbidity and mortality worldwide. Several studies have shown that the severely ill patients have high or very high D-dimer values, and a hypercoagulable state has been described with, in some cases, development of disseminated intravascular coagulation (DIC). A few reports have indicated that there seems to be a higher incidence of venous thromboembolism than expected in otherwise severely ill patients. In this article, we will discuss the prothrombotic changes observed and to what extent they are specific for COVID-19. The incidence of thromboembolic events will be compared with those reported in sepsis and severe influenza A H1N1. The emphasis is on venous events, which have been the most frequently reported events. Finally, the intensity of pharmacological prophylaxis against venous thromboembolism will be discussed.
The pandemic of COVID-19 is affecting almost every country in the world, with the number of cases tested and found infected exceeding two million, with an overall mortality of approximately 7% at the time of writing.[1] There are preliminary reports from China on venous thromboembolism based on a relatively small number of patients.[2] [3] Subsequently, European physicians have reported a higher incidence of thromboembolic events, mainly venous, in patients with COVID-19 pneumonia in the intensive care unit (ICU).[4] Another manifestation of hypercoagulability is DIC, which was not reported in other than the occasional case in the largest published cohorts.[5] [6] [7] On the other hand, abnormalities in the coagulation tests, meeting previously defined criteria for DIC, were observed during the terminal days in 71% of nonsurvivors in another cohort from Wuhan, China.[8]
These preliminary findings generate several questions, some which are as follows:
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What are the indicators of hypercoagulability in COVID-19 infection?
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Is the hypercoagulability specific for COVID-19 infection?
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Does the hypercoagulability result in a higher incidence of thromboembolism than in other patients with severe infection in the ICU?
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If so, is it justified to use higher than standard doses of pharmacological prophylaxis against thromboembolism in these patients?
It should be recognized that the data on this infection are rapidly emerging and that information obtained from countries in Europe or North America might differ from those in China due to variations in ethnic susceptibility, environmental conditions (e.g., pollution and health care resources availability), diagnostic routines, and prophylaxis regimens. Therefore, any assumptions or conclusions drawn in this article can be proven wrong after a short time.
Publication History
Article published online:
11 May 2020
© 2020. Thieme. All rights reserved.
Thieme Medical Publishers
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References
- 1 Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. (JHU). Coronavirus COVID-19 Global Cases. Available at: www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 . Accessed April 13, 2020
- 2 Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiol Cardiothorac Imaging 2020; 2 (02) e200067
- 3 Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; (e-pub ahead of print) DOI: 10.1111/jth.14830.
- 4 Klok FA, Kruip MJHA, van der Meer NJM. et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; (e-pub ahead of print) DOI: 10.1016/j.thromres.2020.1004.1013.
- 5 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; (e-pub ahead of print) DOI: 10.1056/NEJMoa2002032.
- 6 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
- 7 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
- 8 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (04) 844-847
- 9 Ma C, Gu J, Hou P. et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxiv 2020; (e-pub ahead of print) DOI: 10.1101/2020.03.17.20037572.
- 10 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033-1034
- 11 Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood 2019; 133 (09) 906-918
- 12 Gaertner F, Massberg S. Blood coagulation in immunothrombosis-at the frontline of intravascular immunity. Semin Immunol 2016; 28 (06) 561-569
- 13 Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res 2019; 181: 77-83
- 14 Prchal JT. Hypoxia and thrombosis. Blood 2018; 132 (04) 348-349
- 15 Iba T, Levi M, Levy JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation. Semin Thromb Hemost 2020; 46 (01) 89-95
- 16 Luo W, Yu H, Gou J. et al. Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19). Preprints 2020 , 2020020407
- 17 Han M, Yan W, Huang Y. et al. The nucleocapsid protein of SARS-CoV induces transcription of hfgl2 prothrombinase gene dependent on C/EBP alpha. J Biochem 2008; 144 (01) 51-62
- 18 Gralinski LE, Bankhead III A, Jeng S. et al. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. MBio 2013; 4 (04) e00271-13
- 19 Shorr AF, Williams MD. Venous thromboembolism in critically ill patients. Observations from a randomized trial in sepsis. Thromb Haemost 2009; 101 (01) 139-144
- 20 Cook D, Meade M, Guyatt G. et al; PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011; 364 (14) 1305-1314
- 21 Ye Z, Zhang Y, Wang Y, Huang Z, Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Eur Radiol 2020; (e-pub ahead of print) DOI: 10.1007/s00330-020-06801-0.
- 22 Aibar J, Schulman S. New-onset atrial fibrillation in sepsis: a narrative review. Semin Thromb Hemost 2020 . In press
- 23 Centers for Disease Control and Prevention (CDC). Intensive-care patients with severe novel influenza A (H1N1) virus infection - Michigan, June 2009. MMWR Morb Mortal Wkly Rep 2009; 58 (27) 749-752
- 24 Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian MD. Pandemic H1N1 influenza infection and vascular thrombosis. Clin Infect Dis 2011; 52 (02) e14-e17
- 25 Avnon LS, Munteanu D, Smoliakov A, Jotkowitz A, Barski L. Thromboembolic events in patients with severe pandemic influenza A/H1N1. Eur J Intern Med 2015; 26 (08) 596-598
- 26 Agarwal PP, Cinti S, Kazerooni EA. Chest radiographic and CT findings in novel swine-origin influenza A (H1N1) virus (S-OIV) infection. AJR Am J Roentgenol 2009; 193 (06) 1488-1493
- 27 Harms PW, Schmidt LA, Smith LB. et al. Autopsy findings in eight patients with fatal H1N1 influenza. Am J Clin Pathol 2010; 134 (01) 27-35
- 28 Lippi G, Franchini M, Favaloro EJ. Influenza and cardiovascular disease: does swine-origin, 2009 H1N1 flu virus represent a risk factor, an acute trigger, or both?. Semin Thromb Hemost 2010; 36 (01) 49-58
- 29 Marongiu F, Mameli A, Grandone E, Barcellona D. Pulmonary thrombosis: a clinical pathological entity distinct from pulmonary embolism?. Semin Thromb Hemost 2019; 45 (08) 778-783
- 30 American Society of Hematology. COVID-19 and VTE/Anticoagulation: Frequently Asked Questions. Available at: www.hematology.org/covid-19/covid-19-and-vte-anticoagulation . Accessed April 13, 2020
- 31 Helms J, Tacquard C, Severac F. et al. High risk of thrombosis in patients in severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Medicine 2020 (epub ahead of print) doi: 10.1007/s00134-020-06062-x
- 32 Middeldorp S, Coppens M, van Haaps TF. et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020 . doi: 10.1111/jth.14888. [Epub ahead of print]