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COVID-19 and Life Threatening Cardiac and Cerebellar Thromboembolic Events in Cardiac Operations

Tuesday, April 27, 2021

Raheel FA, Hadjinikolaou L, Mimic B, Khan SA, Darbar A, Mariscalco G. COVID-19 and Life Threatening Cardiac and Cerebellar Thromboembolic Events in Cardiac Operations. April 2021. doi:10.25373/ctsnet.14495829

There are several reported cases that have showed that COVID-19 is a highly thrombogenic disease. The release of cytokines during cardiopulmonary bypass plus COVID 19 related thrombogenic factors can trigger life-threatening thromboembolic events as we have experienced with these two young patients.

Myocarditis was rare in COVID-19 in an autopsy population of 277 subjects; however, COVID-19-related cardiovascular histopathologic findings, such as macro or microvascular thrombi were reported in nearly half of the cases 11. There was no definitive evidence of direct myocardial infection detected in a detailed histopathologic, immune-histochemical, ultrastructural, and molecular cardiac series; however, COVID-19 cases frequently have cardiac fibrin micro-thrombi 12. SARS-CoV-2 stimulates extracellular neutrophils traps (NETs) in a process called NETosis in association with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils; the ROS-NET pathway plays a role in thrombosis formation 13. The SARS-CoV2 virus directly infects immune cells and dysregulates the immune system. It also infects endothelial cells and damages them, activates leukocytes to potentiate pro-coagulant states via the release of intravascular tissue factor, platelet activation, NETo sis, and inhibition of anticoagulant mechanisms 14. The presence of SARS-CoV-2 virus within the endothelial cells suggests that direct viral infection induces inflammation of the endothelium as well as host inflammatory response which may further contribute to endothelial injury 15,16.

Fatal COVID-19 is characterized as a cytokine release syndrome (CRS) that is induced by a cytokine storm with high mortality 17. Cytokines are the mediators of inflammation and immunity. Cytokines modulate the recruitment and activation of leukocytes, activate platelet aggregation, bind to endothelial cells, immobilize leukocytes resulting in vascular occlusion, and thrombosis 18. The raised CRP of these patients could be an indicator of the severity of illness due to COVID-19 19,20 or just a response of recent surgery. Even patients with mild forms of COVID-19 remain at risk for COVID-19-associated coronary and cerebral thrombosis, and coagulopathy 21. Arterial thromboembolic events were also noticed in 9.6% of admitted patients with severe COVID-19 infection 23.
Additionally, both patients were asymptomatic prior to the operation and had negative upper respiratory tract COVID 19 swabs. SARS-CoV-2 RNA was detected in postoperative Broncho-alveolar Lavage by PCR 1. They remained stable during the initial postoperative period, then developed major life-threatening thromboembolic events. The question arises whether bronchioalveolar lavage to test for SARS-CoV-2 immediately post intubation should be routinely carried out, for those patients who had recent negative swabs? If the result is positive and available prior to start of the operation, surgeons can postpone non-urgent/emergency operations. However, if a positive result is obtained during/after the operation, the aim should be to keep a hypo-coagulable status. Combination therapy with antiplatelet and treatment dose anticoagulation should be considered at very early postoperative hours in SARS-CoV-2 positive patients. Furthermore, these anticoagulant therapies can also be considered in adjuvant to other therapies in severe COVID 19 infections. A randomized clinical trial called DICER is testing dipyridamole in patients with confirmed coronavirus (SARS-CoV)-2 infections, to assess if it is effective in reducing excessive blood clots 24.


Thank you to Dr Hakeem Oluwatoyin Yusuff, Dr Meenal Rana, Dr Patricia Romero Palomino and Professor Sanjay Agrawal for their contribution in the management.


  1. Elizabeth Smith, Wei Zhen, Ryhana Manji, Deborah Schron, Scott Duong, Gregory J. Berry Journal of Clinical Microbiology Aug 2020, 58 (9) e01134-20; DOI: 10.1128/JCM.01134-20
  2. Udo Boeken, Alexander Assmann, Arash Mehdiani, Payam Akhyari, Artur Lichtenberg, Open chest management after cardiac operations: outcome and timing of delayed sternal closure, European Journal of Cardio-Thoracic Surgery, Volume 40, Issue 5, November 2011, Pages 1146 1150,
  3. Shalabi RI, Amin M, Ayed AK, Shuhiber H. Delayed sternal closure is a life saving decision. Ann Thorac Cardiovasc Surg. 2002 Aug;8(4):220-3. PMID: 12472386.
  4. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10. PMID: 32291094; PMCID: PMC7146714.
  5. Juan R. Rey, Santiago Jiménez Valero, Dolores Poveda Pinedo, Jose L. Merino, José Luis López-Sendón, Juan Caro-Codón, COVID-19 and simultaneous thrombosis of two coronary arteries, Revista Española de Cardiologìa (English Edition), Volume 73, Issue 8,2020, Pages 676-677, ISSN 1885-5857,
  6. Sandra Zendjebil, Michel Zeitouni, Marc Batonga, Nathan El Bèze, Paul Guedeney, Jean-Philippe Collet, Rémi Choussat, Johanne Silvain, Gilles Montalescot, Acute Multivessel Coronary Occlusion Revealing COVID-19 in a Young Adult, JACC: Case Reports, Volume 2, Issue 9, 2020, Pages 1297-1301, ISSN 2666-0849
  7. Shams A, Ata F, Mushtaq K, Munir W, Yousaf Z. Coronary thrombosis in a young male with COVID-19. IDCases. 2020 Jul 25;21:e00923. doi: 10.1016/j.idcr.2020.e00923. PMID: 32754426; PMCID: PMC7381412.
  8. Harari, R, Bangalore, S, Chang, E, Shah, B. COVID‐19 complicated by acute myocardial infarction with extensive thrombus burden and cardiogenic shock. Catheter Cardiovasc Interv. 2020; 1– 6.
  9. Alicia Prieto-Lobato, Raquel Ramos-Martínez, Nuria Vallejo-Calcerrada, Miguel Corbí-Pascual, Juan G. Córdoba-Soriano, A Case Series of Stent Thrombosis During the COVID-19 Pandemic, JACC: Case Reports, Volume 2, Issue 9, 2020, Pages 1291-1296, ISSN 2666-0849,
  10. Hinterseer, M., Zens, M., Wimmer, R.J. et al. Acute myocardial infarction due to coronary stent thrombosis in a symptomatic COVID-19 patient. Clin Res Cardiol (2020).
  11. Marc K. Halushka, Richard S. Vander Heide, Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations, Cardiovascular Pathology, Volume 50, 2021,107300, ISSN 1054-8807,
  12. Bois MC, Boire NA, Layman AJ, Aubry MC, Alexander MP, Roden AC, Hagen CE, Quinton RA, Larsen C, Erben Y, Majumdar R, Jenkins SM, Kipp BR, Lin PT, Maleszewski JJ. COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart. Circulation. 2020 Nov 16. doi: 10.1161/CIRCULATIONAHA.120.050754. Epub ahead of print. PMID: 33197204.
  13. Arcanjo, A., Logullo, J., Menezes, C.C.B. et al. The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19). Sci Rep 10, 19630 (2020).
  14. ayarangaiah A, Kariyanna PT, Chen X, Jayarangaiah A, Kumar A. COVID-19-Associated Coagulopathy: An Exacerbated Immunothrombosis Response. Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620943293. doi: 10.1177/1076029620943293. PMID: 32735131; PMCID: PMC7401047.
  15. Zsuzsanna Varga,Andreas J Flammer,Peter Steiger,Martina Haberecker,Rea Andermatt,Annelies S Zinkernagel,Mandeep R Mehra,Reto A Schuepbach,Frank Ruschitzka,Holger Moch Publication: The Lancet. Publisher: Elsevier, Date: 2–8 May 2020. DOI:
  16. M Ackermann, SE Verleden, M Kuehnel, A Haverich, T Welte, F Laenger, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19 N Engl J Med, 383 (2) (2020), pp. 120-128, 10.1056/NEJMoa2015432
  17. Hojyo, S., Uchida, M., Tanaka, K. et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regener 40, 37 (2020).
  18. Dosquet C, Weill D, Wautier JL. Cytokines and thrombosis. Journal of Cardiovascular Pharmacology. 1995 ;25 Suppl 2:S13-9. DOI: 10.1097/00005344-199500252-00004.
  19. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4. doi: 10.1016/j.jaci.2020.05.008. Epub 2020 May 18. PMID: 32425269; PMCID: PMC7233239.
  20. Poggiali E, Zaino D, Immovilli P, et al. Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2020 Oct;509:135-138. DOI: 10.1016/j.cca.2020.06.012.
  21. Lauren S Ranard, David J Engel, Ajay J Kirtane, Amirali Masoumi, Coronary and cerebral thrombosis in a young patient after mild COVID-19 illness: a case report, European Heart Journal - Case Reports, Volume 4, Issue 5, October 2020, Pages 1–5,
  22. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10. PMID: 32291094; PMCID: PMC7146714.
  23. C. de Roquetaillade,B.G. Chousterman,D. Tomasoni,M. Zeitouni,E. Houdart,A. Guedon,P. Reiner,R. Bordier,E. Gayat,G. Montalescot,M. Metra,A. Mebazaa. Unusual arterial thrombotic events in Covid-19 patients. Publication: International Journal of Cardiology. Publisher: Elsevier. Date: 15 January 2021 DOI:
  24. NCT04391179


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