https://doi.org/10.4081/monaldi.2022.1958
SARS-CoV-2 induced coagulopathy and potential role of anticoagulation: Scoping review of literature
Submitted: May 31, 2021
Accepted: October 5, 2021
Published: January 26, 2022
Accepted: October 5, 2021
Abstract Views: 1662
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can vary on a spectrum of asymptomatic disease to rarer manifestations like hypercoagulability especially among elderly patients admitted in the intensive care unit (ICU) and those with preexisting comorbidities. The exact mechanism behind this phenomenon is still unclear, however studies have shown an association with elevated cytokines and severe inflammatory response which encompasses this disease. Hypercoagulability can be limited to the lungs, or present as systemic manifestations of arterial and venous thrombosis leading to mortal outcomes. Thus, careful evaluation of risk factors should be performed by physicians and treatment with anticoagulants should be modified accordingly. All Coronavirus Disease 2019 (COVID-19) in-patients should receive thromboprophylactic therapy, with increased dosages administered to patients with increased disease severity or those with a high risk. D-dimer levels and sepsis-induced coagulopathy (SIC) score aid in identifying high risk patients and predicting outcome. This article highlights the pathophysiology behind hypercoagulability, its clinical associations and discusses therapeutic modalities to combat this fatal consequence of SARS-CoV-2.
Shi Y, Wang G, Cai X-P, et al. An overview of COVID-19. J Zhejiang Univ Sci B 2020;21:343-60.
DOI: https://doi.org/10.1631/jzus.B2000083
Mortus JR, Manek SE, Brubaker LS, et al. Thromboelastographic results and hypercoagulability syndrome in patients with coronavirus disease 2019 who are critically ill. JAMA Netw Open 2020;3:e2011192-e.
DOI: https://doi.org/10.1001/jamanetworkopen.2020.11192
Amawi H, Abu Deiab GaI, A Aljabali AA, et al. COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics. Ther Deliv 2020;11:245-68.
DOI: https://doi.org/10.4155/tde-2020-0035
Vinayagam S, Sattu K. SARS-CoV-2 and coagulation disorders in different organs. Life Sci 2020;260:118431.
DOI: https://doi.org/10.1016/j.lfs.2020.118431
Abou-Ismail MY, Diamond A, Kapoor S, et al. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thromb Res 2020;194:101-15.
DOI: https://doi.org/10.1016/j.thromres.2020.06.029
Campbell CM, Kahwash R. Will complement inhibition be the new target in treating COVID-19–related systemic thrombosis? Circulation 2020;141:1739-41.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.047419
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13.
DOI: https://doi.org/10.1016/S0140-6736(20)30211-7
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med 2020;217:e20200652.
DOI: https://doi.org/10.1084/jem.20200652
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8.
DOI: https://doi.org/10.1016/S0140-6736(20)30937-5
Idell S. Coagulation, fibrinolysis, and fibrin deposition in acute lung injury. Crit Care Med 2003;31:S213-20.
DOI: https://doi.org/10.1097/01.CCM.0000057846.21303.AB
Hanley B, Lucas SB, Youd E, et al. Autopsy in suspected COVID-19 cases. J Clin Pathol 2020;73:239-42.
DOI: https://doi.org/10.1136/jclinpath-2020-206522
Matos MF, Lourenço DM, Orikaza CM, et al. The role of IL-6, IL-8 and MCP-1 and their promoter polymorphisms IL-6-174GC, IL-8-251AT and MCP-1-2518AG in the risk of venous thromboembolism: a case-control study. Thromb Res 2011;128:216-20.
DOI: https://doi.org/10.1016/j.thromres.2011.04.016
Bautista-Vargas M, Bonilla-Abadía F, Cañas CA. Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19. J Thromb Thrombolysis 2020;50:479-83.
DOI: https://doi.org/10.1007/s11239-020-02172-x
Cui S, Chen S, Li X, et al. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020;18:1421-4.
DOI: https://doi.org/10.1111/jth.14830
Lorenzo C, Francesca B, Francesco P, et al. Acute pulmonary embolism in COVID-19 related hypercoagulability. J Thromb Thrombolysis 2020;50:223-6.
DOI: https://doi.org/10.1007/s11239-020-02160-1
Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020;382:e38.
DOI: https://doi.org/10.1056/NEJMc2007575
Dorgalaleh A, Dabbagh A, Tabibian S, et al. Patients with congenital bleeding disorders appear to be less severely affected by SARS-CoV-2: Is inherited hypocoagulability overcoming acquired hypercoagulability of coronavirus disease 2019 (COVID-19)? Semin Thromb Hemost 2020;46:853-5.
DOI: https://doi.org/10.1055/s-0040-1713435
Amgalan A, Othman M. Exploring possible mechanisms for COVID‐19 induced thrombocytopenia: Unanswered questions. J Thromb Haemost 2020;18:1514-6.
DOI: https://doi.org/10.1111/jth.14832
Bompard F, Monnier H, Saab I, et al. Pulmonary embolism in patients with Covid-19 pneumonia. Eur Respir J 2021;206:29-32.
DOI: https://doi.org/10.1016/j.thromres.2021.08.003
Panigada M, Bottino N, Tagliabue P, et al. Hypercoagulability of COVID‐19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemos 2020;18:1738-42.
DOI: https://doi.org/10.1111/jth.14850
Guan W-J, Ni Z-Y, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
DOI: https://doi.org/10.1056/NEJMoa2002032
Casey K, Iteen A, Nicolini R, Auten J. COVID-19 pneumonia with hemoptysis: acute segmental pulmonary emboli associated with novel coronavirus infection. Am J Emerg Med 2020;38:1544.e1-e3.
DOI: https://doi.org/10.1016/j.ajem.2020.04.011
Ranucci M, Ballotta A, Di Dedda U, et al. The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome. J Thromb Haemost 2020;18:1747-51.
DOI: https://doi.org/10.1111/jth.14854
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;18:844-7.
DOI: https://doi.org/10.1111/jth.14768
Wichmann D, Sperhake J-P, Lütgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020;173:268-77.
DOI: https://doi.org/10.7326/L20-1206
Lodigiani C, Iapichino G, Carenzo L, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020;191:9-14.
DOI: https://doi.org/10.1016/j.thromres.2020.04.024
Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094-9.
DOI: https://doi.org/10.1111/jth.14817
Emert R, Shah P, Zampella JG. COVID-19 and hypercoagulability in the outpatient setting. Thromb Res 2020;192:122-3.
DOI: https://doi.org/10.1016/j.thromres.2020.05.031
Dane B, Smereka P, Wain R, et al. Hypercoagulability in COVID-19: Identification of arterial and venous thromboembolism in the abdomen, pelvis, and lower extremities. AJR Am J Roentgenol 2021;216:104-5.
DOI: https://doi.org/10.2214/AJR.20.23617
Klok F, Kruip M, Van der Meer N, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145-7.
DOI: https://doi.org/10.1016/j.thromres.2020.04.013
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;395:1054-62.
DOI: https://doi.org/10.1016/S0140-6736(20)30566-3
Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J 2020;41:1858.
DOI: https://doi.org/10.1093/eurheartj/ehaa254
Klok FA, Kruip M, Van Der Meer N, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res 2020;191:148-50.
DOI: https://doi.org/10.1016/j.thromres.2020.04.041
Criel M, Jaeken J, Van Kerrebroeck M, et al. Venous thromboembolism in SARS-CoV-2 patients: only a problem in ventilated ICU patients, or is there more to it? Eur Respir J 2020;56:2001201.
DOI: https://doi.org/10.1183/13993003.01201-2020
Liu Y, Du X, Chen J, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect 2020;81:e6-e12.
DOI: https://doi.org/10.1016/j.jinf.2020.04.002
Chong PY, Chui P, Ling AE, et al. Analysis of deaths during the severe acute respiratory syndrome (SARS) epidemic in Singapore: challenges in determining a SARS diagnosis. Arch Pathol Lab Med 2004;128:195-204.
DOI: https://doi.org/10.5858/2004-128-195-AODDTS
Wong C, Lam C, Wu A, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol 2004;136:95-103.
DOI: https://doi.org/10.1111/j.1365-2249.2004.02415.x
Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID‐19. J Thromb Haemost 2020;18:1559-61.
DOI: https://doi.org/10.1111/jth.14849
Iba T, Thachil J. Present and future of anticoagulant therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a perspective from Japan. Int J Hematol 2016;103:253-61.
DOI: https://doi.org/10.1007/s12185-015-1904-z
Opal SM. Interactions between coagulation and inflammation. Scand J Infect Dis 2003;35:545-54.
DOI: https://doi.org/10.1080/00365540310015638
Duan Q, Gong Z, Song H, et al. Symptomatic venous thromboembolism is a disease related to infection and immune dysfunction. Int J Med Sci 2012;9:453.
DOI: https://doi.org/10.7150/ijms.4453
Halasz G, Di Spigno F, Piepoli M, et al. [Late occurrence of pulmonary embolsim in SARS-CoV-2 pneumonia: a case series].[Article in Italian]. G Ital Cardiol (Rome) 2020;21:523-5.
Bangalore S, Sharma A, Slotwiner A, et al. ST-segment elevation in patients with Covid-19-a case series. N Engl J Med 2020;382:2478-80.
DOI: https://doi.org/10.1056/NEJMc2009020
Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020;5:802-10.
DOI: https://doi.org/10.1001/jamacardio.2020.0950
Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811-8.
DOI: https://doi.org/10.1001/jamacardio.2020.1017
Tavazzi G, Pellegrini C, Maurelli M, et al. Myocardial localization of coronavirus in COVID‐19 cardiogenic shock. Eur J Heart Fail 2020;22:911-5.
DOI: https://doi.org/10.1002/ejhf.1828
Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of coronavirus disease 2019 (COVID-19) with myocardial injury and mortality. JAMA Cardiol 2020;5:751-3.
DOI: https://doi.org/10.1001/jamacardio.2020.1105
Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neuro. 2020;77:683-90.
DOI: https://doi.org/10.1001/jamaneurol.2020.1127
Ezpeleta D, Garcia D. [Manual COVID-19 para el neurólogo general].[in Spanish]. Sociedad Española de Neurología, Ediciones SEN; 2020. Available from: https://www.sen.es/pdf/2020/Manual_neuroCOVID-19_SEN.pdf
Umapathi T, Kor AC, Venketasubramanian N, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol 2004;251:1227-31.
DOI: https://doi.org/10.1007/s00415-004-0519-8
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50:e344-e418.
DOI: https://doi.org/10.1161/STR.0000000000000211
Zhang Y, Cao W, Xiao M, et al. [Clinical and coagulation characteristics in 7 patients with critical COVID-2019 pneumonia and acro-ischemia].[Article in Chinese]. Zhonghua Xue Ye Xue Za Zhi 2020;41:302-7.
Cao Y, Liu X, Xiong L, Cai K. Imaging and clinical features of patients with 2019 novel coronavirus SARS‐CoV‐2: A systematic review and meta‐analysis. J Med Virol 2020;92:1449-59.
DOI: https://doi.org/10.1002/jmv.25822
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection - a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect 2020;9:727-32.
DOI: https://doi.org/10.1080/22221751.2020.1746199
Li T, Lu H, Zhang W. Clinical observation and management of COVID-19 patients. Emerg Microbes Infect 2020;9:687-90.
DOI: https://doi.org/10.1080/22221751.2020.1741327
Magro C, Mulvey JJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res 2020;220:1-13.
DOI: https://doi.org/10.1016/j.trsl.2020.04.007
Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. J Thromb Haemost 2020;18:1023-6.
DOI: https://doi.org/10.1111/jth.14810
Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol 2020;21:335-7.
DOI: https://doi.org/10.1016/S1470-2045(20)30096-6
Spyropoulos AC, Ageno W, Barnathan ES. Hospital-based use of thromboprophylaxis in patients with COVID-19. Lancet 2020;395e75.
DOI: https://doi.org/10.1016/S0140-6736(20)30926-0
Paranjpe I, Fuster V, Lala A, et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 2020;76:122-4.
DOI: https://doi.org/10.1016/j.jacc.2020.05.001
Asakura H, Ogawa H. Potential of heparin and nafamostat combination therapy for COVID‐19. J Thromb Haemost 2020;18:1521-2.
DOI: https://doi.org/10.1111/jth.14858
National Institutes of Health. Antithrombotic therapy in patients with COVID-19. 2020. available from: https://www.covid19treatmentguidelines.nih.gov/therapies/antithrombotic-therapy/
Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020;46:1089-98.
DOI: https://doi.org/10.1007/s00134-020-06062-x
Miesbach W, Makris M. COVID-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost 2020;26:1076029620938149.
DOI: https://doi.org/10.1177/1076029620938149
Thachil J, Tang N, Gando S, et al. Type and dose of heparin in Covid‐19: Reply. J Thromb Haemost 2020;18:2063-4.
DOI: https://doi.org/10.1111/jth.14870
Mummery RS, Rider CC. Characterization of the heparin-binding properties of IL-6. J Immunol 2000;165:5671-9.
DOI: https://doi.org/10.4049/jimmunol.165.10.5671
Testa S, Paoletti O, Giorgi-Pierfranceschi M, Pan A. Switch from oral anticoagulants to parenteral heparin in SARS-CoV-2 hospitalized patients. Intern Emerg Med 2020;15:751-3.
DOI: https://doi.org/10.1007/s11739-020-02331-1
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Zehra Naseem, Muhammad Mussab Khakwani, Maaha Ayub, Ahmed Ayaz, Bushra Jamil, and Ainan Arshad. 2022. “SARS-CoV-2 Induced Coagulopathy and Potential Role of Anticoagulation: Scoping Review of Literature”. Monaldi Archives for Chest Disease 92 (4). https://doi.org/10.4081/monaldi.2022.1958.
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