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Current Medical Imaging

Author(s): Shawn Lee, Joseph Gunderson and Raza Mushtaq*

DOI: 10.2174/1573405619666230216112751

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Thromboembolic Disorder in COVID-19 Infection

Article ID: e160223213721 Pages: 12

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Abstract

Coronavirus (COVID-19) is a global pandemic with over 600 million cases identified. In addition to extensive pulmonary complications of COVID-19, one feature unique to many patients with severe COVID-19 infections is coagulopathy with a rising prevalence of multi-systemic thromboembolic manifestations. Global data suggests a relationship between coagulopathy and mortality. In this review, we highlight multiple COVID-19 thromboembolic complications with emphasis on pathophysiology, clinical management, and radiological manifestations.

Keywords: Coronavirus, COVID-19, thromboembolic disorders, coagulopathy, China, coagulation parameters.

Graphical Abstract

[1]
World Health Organization (WHO). Coronavirus WHO. Available from: https://covid19.who.int
[2]
Grillet F, Behr J, Calame P, Aubry S, Delabrousse E. Acute Pulmonary Embolism Associated with COVID-19 pneumonia detected with pulmonary CT angiography. Radiology 2020; 296(3): E186-8.
[http://dx.doi.org/10.1148/radiol.2020201544] [PMID: 32324103]
[3]
Oudkerk M, Büller HR, Kuijpers D, et al. Diagnosis, prevention, and treatment of thromboembolic complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology 2020; 297(1): E216-22.
[http://dx.doi.org/10.1148/radiol.2020201629] [PMID: 32324101]
[4]
Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiol Cardiothorac Imaging 2020; 2(2): e200067.
[http://dx.doi.org/10.1148/ryct.2020200067] [PMID: 33778561]
[5]
Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: A random association? Eur Heart J 2020; 41(19): 1858.
[http://dx.doi.org/10.1093/eurheartj/ehaa254] [PMID: 32227120]
[6]
Goeijenbier M, van Wissen M, van de Weg C, et al. Review: Viral infections and mechanisms of thrombosis and bleeding. J Med Virol 2012; 84(10): 1680-96.
[http://dx.doi.org/10.1002/jmv.23354] [PMID: 22930518]
[7]
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; 191: 145-7.
[http://dx.doi.org/10.1016/j.thromres.2020.04.013]
[8]
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; 18(6): 1421-4.
[http://dx.doi.org/10.1111/jth.14830] [PMID: 32271988]
[9]
Léonard-Lorant I, Delabranche X, Séverac F, et al. Acute Pulmonary Embolism in Patients with COVID-19 at CT angiography and relationship to d -Dimer levels. Radiology 2020; 296(3): E189-91.
[http://dx.doi.org/10.1148/radiol.2020201561] [PMID: 32324102]
[10]
Cau R, Pacielli A, Fatemeh H, et al. Complications in COVID-19 patients: Characteristics of pulmonary embolism. Clin Imaging 2021; 77: 244-9.
[http://dx.doi.org/10.1016/j.clinimag.2021.05.016] [PMID: 34029929]
[11]
Gong X, Yuan B, Yuan Y. Incidence and prognostic value of pulmonary embolism in COVID-19: A systematic review and meta-analysis. PLoS One 2022; 17(3): e0263580.
[http://dx.doi.org/10.1371/journal.pone.0263580] [PMID: 35286316]
[12]
Levi M, van der Poll T. Coagulation and sepsis. Thromb Res 2017; 149: 38-44.
[http://dx.doi.org/10.1016/j.thromres.2016.11.007] [PMID: 27886531]
[13]
Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: A retrospective analysis of a nationwide survey. BMJ Open 2017; 7(9): e017046.
[http://dx.doi.org/10.1136/bmjopen-2017-017046] [PMID: 28963294]
[14]
Semeraro N, Ammollo CT, Semeraro F, Colucci M. Sepsis-associated disseminated intravascular coagulation and thromboembolic disease. Mediterr J Hematol Infect Dis 2010; 2(3): e2010024.
[http://dx.doi.org/10.4084/mjhid.2010.024] [PMID: 21415977]
[15]
van Gorp ECM, Suharti C, ten Cate H, et al. Review: Infectious diseases and coagulation disorders. J Infect Dis 1999; 180(1): 176-86.
[http://dx.doi.org/10.1086/314829] [PMID: 10353876]
[16]
Iba T, Levy JH, Warkentin TE, Thachil J, Poll T, Levi M. Diagnosis and management of sepsis‐induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost 2019; 17(11): 1989-94.
[http://dx.doi.org/10.1111/jth.14578] [PMID: 31410983]
[17]
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): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[18]
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020; 323(11): 1061-9.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[19]
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(4): 844-7.
[http://dx.doi.org/10.1111/jth.14768] [PMID: 32073213]
[20]
Terra POC, Donadel CD, Oliveira LC, et al. Neutrophil‐to‐lymphocyte ratio and D‐dimer are biomarkers of death risk in severe COVID‐19: A retrospective observational study. Health Sci Rep 2022; 5(2): e514.
[http://dx.doi.org/10.1002/hsr2.514] [PMID: 35155834]
[21]
Kutsogiannis DJ, Alharthy A, Balhamar A, et al. Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19. Front Med (Lausanne) 2022; 9: 800241.
[http://dx.doi.org/10.3389/fmed.2022.800241] [PMID: 35308552]
[22]
Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with covid-19: An autopsy series from New Orleans. Lancet Respir Med 2020; 8(7): 681-6.
[http://dx.doi.org/10.1101/2020.04.06.20050575]
[23]
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395(10234): 1417-8.
[http://dx.doi.org/10.1016/S0140-6736(20)30937-5] [PMID: 32325026]
[24]
Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, thrombosis, kidney failure, and diabetes: Is covid-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med 2020; 9(5): 1417.
[25]
Huertas A, Montani D, Savale L, et al. Endothelial cell dysfunction: A major player in SARS-CoV-2 infection (COVID-19)? Eur Respir J 2020; 56(1): 2001634.
[http://dx.doi.org/10.1183/13993003.01634-2020]
[26]
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.
[http://dx.doi.org/10.1016/j.trsl.2020.04.007] [PMID: 32299776]
[27]
Yu J, Yuan X, Chen H, Chaturvedi S, Braunstein EM, Brodsky RA. Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. Blood 2020; 136(18): 2080-9.
[http://dx.doi.org/10.1182/blood.2020008248] [PMID: 32877502]
[28]
Fernández S, Moreno-Castaño AB, Palomo M, et al. Distinctive biomarker features in the endotheliopathy of COVID-19 and septic syndromes. Shock 2022; 57(1): 95-105.
[http://dx.doi.org/10.1097/SHK.0000000000001823] [PMID: 34172614]
[29]
Castanha PMS, Tuttle DJ, Kitsios GD, et al. Contribution of coronavirus-specific Immunoglobulin G responses to complement overactivation in patients with severe coronavirus disease 2019. J Infect Dis 2022; 226(5): 766-77.
[http://dx.doi.org/10.1093/infdis/jiac091]
[30]
Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol 2020; 5(7): 831-40.
[http://dx.doi.org/10.1001/jamacardio.2020.1286] [PMID: 32219363]
[31]
Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res 2020; 116(6): 1097-100.
[http://dx.doi.org/10.1093/cvr/cvaa078] [PMID: 32227090]
[32]
Li Z, Wu M, Yao J, et al. Caution on kidney dysfunctions of COVID-19 patients. MedRxiv 2020; 12: 2020-02.
[33]
Pan X, Xu D, Zhang H, Zhou W, Wang L, Cui X. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: A study based on single-cell transcriptome analysis. Intensive Care Med 2020; 46(6): 1114-6.
[http://dx.doi.org/10.1007/s00134-020-06026-1] [PMID: 32236644]
[34]
Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney international 2020; 97(5): 829-38.
[http://dx.doi.org/10.1101/2020.02.18.20023242]
[35]
Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020; 98(1): 219-27.
[http://dx.doi.org/10.1016/j.kint.2020.04.003] [PMID: 32327202]
[36]
Fiore JR, Ciarallo M, Di Stefano M, et al. Severe systemic thrombosis in a young COVID-19 patient with a rare homozygous prothrombin G20210A mutation. Infez Med 2021; 29(2): 259-62.
[PMID: 34061792]
[37]
Elkattawy S, Alyacoub R, Singh KS, Fichadiya H, Kessler W. Prothrombin G20210A Gene Mutation-Induced Recurrent Deep Vein Thrombosis and Pulmonary Embolism: Case Report and Literature Review. J Investig Med High Impact Case Rep 2022; 10: 1-10.
[http://dx.doi.org/10.1177/23247096211058486] [PMID: 35426321]
[38]
Mat O, Ghisdal L, Massart A, et al. Kidney thrombotic microangiopathy after COVID-19 associated with C3 gene mutation. Kidney Int Rep 2021; 6(6): 1732-7.
[http://dx.doi.org/10.1016/j.ekir.2021.03.897] [PMID: 33851069]
[39]
Krishnappa V, Gupta M, Elrifai M, et al. Atypical hemolytic uremic syndrome: A meta‐analysis of case reports confirms the prevalence of genetic mutations and the shift of treatment regimens. Ther Apher Dial 2018; 22(2): 178-88.
[http://dx.doi.org/10.1111/1744-9987.12641] [PMID: 29250893]
[40]
Lee S, Lee CH, Seo MS, Yoo JI. Integrative analyses of genes about venous thromboembolism: An umbrella review of systematic reviews and meta-analyses. Medicine 2022; 101(43): e31162.
[http://dx.doi.org/10.1097/MD.0000000000031162] [PMID: 36316870]
[41]
Simpson S, Kay FU, Abbara S, et al. Radiological Society of North America Expert Consensus Document on Reporting Chest CT findings related to COVID-19: Endorsed by the society of thoracic radiology, the American College of radiology, and RSNA. Radiol Cardiothorac Imaging 2020; 2(2): e200152.
[http://dx.doi.org/10.1148/ryct.2020200152] [PMID: 33778571]
[42]
Kanne JP, Little BP, Chung JH, Elicker BM, Ketai LH. Essentials for radiologists on COVID-19: An update—radiology scientific expert panel. Radiology 2020; 296(2): E113-4.
[http://dx.doi.org/10.1148/radiol.2020200527] [PMID: 32105562]
[43]
Guan W, Liu J, Yu C. CT Findings of Coronavirus Disease (COVID-19) severe pneumonia. AJR Am J Roentgenol 2020; 214(5): W85-6.
[http://dx.doi.org/10.2214/AJR.20.23035] [PMID: 32208010]
[44]
Hosseiny M, Kooraki S, Gholamrezanezhad A, Reddy S, Myers L. Radiology perspective of coronavirus disease 2019 (COVID-19): Lessons from severe acute respiratory syndrome and Middle East respiratory syndrome. AJR Am J Roentgenol 2020; 214(5): 1078-82.
[http://dx.doi.org/10.2214/AJR.20.22969] [PMID: 32108495]
[45]
Bernheim A, Mei X, Huang M, et al. Chest CT findings in coronavirus disease-19 (COVID-19): Relationship to duration of infection. Radiology 2020; 295(3): 200463.
[http://dx.doi.org/10.1148/radiol.2020200463] [PMID: 32077789]
[46]
Pan F, Ye T, Sun P, et al. Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia. Radiology 2020; 295: 715-72.
[PMID: 32053470]
[47]
Revel MP, Parkar AP, Prosch H, et al. COVID-19 patients and the radiology department – advice from the European Society of Radiology (ESR) and the European Society of Thoracic Imaging (ESTI). Eur Radiol 2020; 30(9): 4903-9.
[http://dx.doi.org/10.1007/s00330-020-06865-y] [PMID: 32314058]
[48]
He H, Stein MW, Zalta B, Haramati LB. Pulmonary infarction. J Thorac Imaging 2006; 21(1): 1-7.
[http://dx.doi.org/10.1097/01.rti.0000187433.06762.fb] [PMID: 16538148]
[49]
Casullo J, Semionov A. Reversed halo sign in acute pulmonary embolism and infarction. Acta Radiol 2013; 54(5): 505-10.
[http://dx.doi.org/10.1177/0284185113475797] [PMID: 23395814]
[50]
Godoy MCB, Viswanathan C, Marchiori E, et al. The reversed halo sign: Update and differential diagnosis. Br J Radiol 2012; 85(1017): 1226-35.
[http://dx.doi.org/10.1259/bjr/54532316] [PMID: 22553298]
[51]
Malato A, Dentali F, Siragusa S, et al. The impact of deep vein thrombosis in critically ill patients: A meta-analysis of major clinical outcomes. Blood Transfus 2015; 13(4): 559-68.
[PMID: 26513770]
[52]
Marik PE, Andrews L, Maini B. The incidence of deep venous thrombosis in ICU patients. Chest 1997; 111(3): 661-4.
[http://dx.doi.org/10.1378/chest.111.3.661] [PMID: 9118705]
[53]
Baig AM. Neurological manifestations in COVID‐19 caused by SARS‐CoV‐2. CNS Neurosci Ther 2020; 26(5): 499-501.
[http://dx.doi.org/10.1111/cns.13372] [PMID: 32266761]
[54]
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19–associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 2020; 296(2): E119-20.
[http://dx.doi.org/10.1148/radiol.2020201187] [PMID: 32228363]
[55]
Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of covid-19 in the young. N Engl J Med 2020; 382(20): e60.
[http://dx.doi.org/10.1056/NEJMc2009787] [PMID: 32343504]
[56]
Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol 2020; 5(3): 279-84.
[57]
Paterson RW, Brown RL, Benjamin L, et al. The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings. Brain 2020; 143(10): 3104-20.
[http://dx.doi.org/10.1093/brain/awaa240] [PMID: 32637987]
[58]
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18(5): 1094-9.
[http://dx.doi.org/10.1111/jth.14817] [PMID: 32220112]
[59]
Santoliquido A, Porfidia A, Nesci A, et al. Incidence of deep vein thrombosis among non‐ICU patients hospitalized for COVID‐19 despite pharmacological thromboprophylaxis. J Thromb Haemost 2020; 18(9): 2358-63.
[http://dx.doi.org/10.1111/jth.14992] [PMID: 32633068]
[60]
Mei F, Fan J, Yuan J, et al. Comparison of venous thromboembolism risks between COVID-19 pneumonia and community-acquired pneumonia patients. Arterioscler Thromb Vasc Biol ATVBAHA 2020; 120: 314779.
[61]
Minet C, Potton L, Bonadona A, et al. Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis. Crit Care 2015; 19(1): 287.
[http://dx.doi.org/10.1186/s13054-015-1003-9] [PMID: 26283414]
[62]
Smith K, Krajewski KC, Krajewski MP Jr. Practical considerations in prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19. Am J Health Syst Pharm 2020; 77(21): 1739-45.
[http://dx.doi.org/10.1093/ajhp/zxaa245] [PMID: 32628248]
[63]
Spyropoulos AC, Levy JH, Ageno W, et al. Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID‐19. J Thromb Haemost 2020; 18(8): 1859-65.
[http://dx.doi.org/10.1111/jth.14929] [PMID: 32459046]
[64]
Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2020; 50(1): 72-81.
[http://dx.doi.org/10.1007/s11239-020-02138-z] [PMID: 32440883]
[65]
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135(23): 2033-40.
[http://dx.doi.org/10.1182/blood.2020006000] [PMID: 32339221]
[66]
Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75(23): 2950-73.
[http://dx.doi.org/10.1016/j.jacc.2020.04.031] [PMID: 32311448]
[67]
American Society of Hematology. COVID-19 and VTE/Anticoagulation: Frequently Asked Questions. 2020. Available from: [https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation