Acta Scientific Medical Sciences (ASMS)(ISSN: 2582-0931)

Research Article Volume 6 Issue 3

Interrelationship Between Thrombosis and COVID-19

Malerba Mario*, Barbieri Mariangela, Mondini Lucrezia, Ruggero Luca, Trotta Liliana and Ragnoli Beatrice

Respiratory Unit S. Andrea Hospital, Department of Traslational Medicine, School of Medicine, University Eastern Piedmont, Italy

*Corresponding Author: Malerba Mario, Professor, Respiratory Unit S. Andrea Hospital, Department of Traslational Medicine, School of Medicine, University Eastern Piedmont, Italy.

Received: November 09, 2021; Published: January 17 , 2022


Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2. In March 2020, the World Health Organization officially declared it as pandemic viral infection. Clinical manifestations include fever, dyspnea, cough, but can evolve into acute respiratory distress syndrome (ARDS), and COVID-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease cgan be explained by the increase of coagulation, levels of D dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time, that are important laboratory parameters which indicate the COVID-19 and VTE severity. The main characteristic of immune-thrombosis is the interaction between haemostasis and the innate immune system. The vascular damage in COVID-19 is induced by the endocytosis of SARS-CoV-2 in the host cells, which leads to pyroptosis. This status is a consequence of the direct virus-induced endothelial damage, leukocyte and cytokine-mediated activation of the platelets, release of TF and NETosis, intensified by activation of the complement system. In this review, the aim is providing an overview of the current knowledge on pathogenic mechanisms of thrombosis in different disease states that may occur in COVID-19 and informing on new areas of research.

Keywords: Thrombosis; COVID-19; Hypercoagulation; Inflammatory Cytokine Storm


  1. “WHO COVID-19 dashboard”. (2020).
  2. Harapan Harapan., et al. “Coronavirus disease 2019 (COVID-19): A literature review”. Journal of Infection and Public Health5 (2020): 667-673.
  3. Varga Zsuzsanna., et al. “Endothelial cell infection and endotheliitis in COVID-19”. Lancet (London, England)10234 (2020): 1417-1418.
  4. Ren Bin., et al. “Extremely High Incidence of Lower Extremity Deep Venous Thrombosis in 48 Patients With Severe COVID-19 in Wuhan”. Circulation2 (2020): 181-183.
  5. Kass David A., et al. “Obesity could shift severe COVID-19 disease to younger ages”. Lancet (London, England)10236 (2020): 1544-1545.
  6. Caci Grazia., et al. “COVID-19 and Obesity: Dangerous Liaisons”. Journal of Clinical Medicine8 2511 (2020).
  7. Sanchis-Gomar Fabian., et al. “Obesity and Outcomes in COVID-19: When an Epidemic and Pandemic Collide”. Mayo Clinic Proceedings7 (2020): 1445-1453.
  8. Lafontan Max. “Fat cells: afferent and efferent messages define new approaches to treat obesity”. Annual Review of Pharmacology and Toxicology 45 (2005): 119-146.
  9. Fontana Luigi., et al. “Visceral fat adipokine secretion is associated with systemic inflammation in obese humans”. Diabetes4 (2007): 1010-1013.
  10. Tang Ning., et al. “Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia”. Journal of Thrombosis And Haemostasis : JTH4 (2020): 844-847.
  11. Ackermann Maximilian., et al. “Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19”. The New England Journal of Medicine2 (2020): 120-128.
  12. Bautista-Vargas Mario., et al. “Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19”. Journal of Thrombosis and Thrombolysis3 (2020): 479-483.
  13. Wright Franklin L., et al. “Fibrinolysis Shutdown Correlation with Thromboembolic Events in Severe COVID-19 Infection”. Journal of the American College of Surgeons2 (2020): 193-203.e1.
  14. Tay Matthew Zirui., et al. “The trinity of COVID-19: immunity, inflammation and intervention”. Nature Reviews. Immunology6 (2020): 363-374.
  15. Miesbach Wolfgang and Michael Makris. “COVID-19: Coagulopathy, Risk of Thrombosis, and the Rationale for Anticoagulation”. Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 26 (2020): 1076029620938149.
  16. Huang Wei., et al. “Lymphocyte Subset Counts in COVID-19 Patients: A Meta-Analysis”.  Part A: The Journal of the International Society for Analytical Cytology 97.8 (2020): 772-776.
  17. Terpos Evangelos., et al. “Hematological findings and complications of COVID-19”. American Journal of Hematology7 (2020): 834-847.
  18. Weitz Jeffrey I., et al. “A Test in Context: D-Dimer”. Journal of the American College of Cardiology19 (2017): 2411-2420.
  19. Eljilany Islam and Abdel-Naser Elzouki. “D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review”. Vascular Health and Risk Management 16 (2020): 455-462.
  20. Gao Yong., et al. “Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19”. Journal of Medical Virology7 (2020): 791-796.
  21. Görlinger Klaus., et al. “COVID-19-Associated Coagulopathy and Inflammatory Response: What Do We Know Already and What Are the Knowledge Gaps?”. Anesthesia and Analgesia5 (2020): 1324-1333.
  22. Whyte Claire S., et al. “Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19”. Journal of Thrombosis and Haemostasis: JTH7 (2020): 1548-1555.
  23. Scialo Filippo., et al. “ACE2: The Major Cell Entry Receptor for SARS-CoV-2”. Lung6 (2020): 867-877.
  24. Aleksova Aneta., et al. “Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review”. International Journal of Molecular Sciences9 (2021): 4526.
  25. Wool Geoffrey D and Jonathan L Miller. “The Impact of COVID-19 Disease on Platelets and Coagulation”. Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology1 (2021): 15-27.
  26. Malerba Mario., et al. “Platelet activation as a novel mechanism of atherothrombotic risk in chronic obstructive pulmonary disease”. Expert Review of Hematology4 (2013): 475-483.
  27. Malerba Mario., et al. “The potential role of endothelial dysfunction and platelet activation in the development of thrombotic risk in COPD patients”. Expert Review of Hematology 9 (2017): 821-832.
  28. Violi Francesco., et al. “Thrombosis in Covid-19 and non-Covid-19 pneumonia: role of platelets”. Platelet (2021): 1-9.
  29. Polosa Riccardo., et al. “Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients”. Internal and Emergency Medicine7 (2013): 567-574.
  30. Gupta Neha., et al. “The stimulation of thrombosis by hypoxia”. Thrombosis research 181 (2019): 77-83.
  31. Leyfman Yan., et al. “Potential Immunotherapeutic Targets for Hypoxia Due to COVI-Flu”. Shock (Augusta, Ga.)4 (2020): 438-450.
  32. Iba Toshiaki., et al. “The coagulopathy, endotheliopathy, and vasculitis of COVID-19”. Inflammation Research : Official Journal of the European Histamine Research Society ... [et al.]12 (2020): 1181-1189.
  33. Ruan Qiurong., et al. “Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China”. Intensive Care Medicine5 (2020): 846-848.
  34. Du Fenghe., et al. “COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness”. Journal of Thrombosis and Thrombolysis2 (2021): 313-329.
  35. Wiedmer T., et al. “Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase”. Blood4 (1986): 875-880.
  36. Java Anuja., et al. “The complement system in COVID-19: friend and foe?”. JCI Insight15 (2020): e140711.
  37. Fuchs Tobias A., et al. “Novel cell death program leads to neutrophil extracellular traps”. The Journal of Cell Biology2 (2007): 231-241.
  38. Fuchs Tobias A., et al. “Neutrophil extracellular trap (NET) impact on deep vein thrombosis”. Arteriosclerosis, Thrombosis, and Vascular Biology8 (2012): 1777-1783.
  39. Zuo Yu., et al. “Neutrophil extracellular traps in COVID-19”. JCI Insight11 (2020): e138999.
  40. Sonnweber Thomas., et al. “Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients' performance: a prospective observational cohort study”. Respiratory Research1 (2020): 276.
  41. Levi Sonia., et al. “Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions”. Cells8 (2021): 1969.
  42. Zhang Yan., et al. “Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19”. The New England Journal of Medicine17 (2020): e38.
  43. Goswami Julie., et al. “A Review of Pathophysiology, Clinical Features, and Management Options of COVID-19 Associated Coagulopathy”. Shock (Augusta, Ga.)6 (2021): 700-716.
  44. Stasi Cristina., et al. “Treatment for COVID-19: An overview”. European Journal of Pharmacology 889 (2020): 173644.
  45. Mennuni Marco G., et al. “Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19”. Journal of Thrombosis and Thrombolysis3 (2021): 782-790.
  46. Rentsch Christopher T., et al. “Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study”. BMJ (Clinical Research Ed.) (2021): 372.
  47. Hasan Syed Shahzad., et al. “Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis”. Journal of Thrombosis and Thrombolysis4 (2020): 814-821.
  48. Aleem Abdul and Ahmed J Nadeem. “Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)”. StatPearls, StatPearls Publishing, 18 July (2021).
  49. Oldenburg Johannes., et al. “Diagnosis and Management of Vaccine-Related Thrombosis following AstraZeneca COVID-19 Vaccination: Guidance Statement from the GTH”. Hamostaseologie3 (2021): 184-189.
  50. Winton centre for Risk evidence Communication. “Communicating the potential benefits and harms of the Astra-Zeneca COVID-19 vaccine” (2021).


Citation: Malerba Mario., et al. “Interrelationship Between Thrombosis and COVID-19”.Acta Scientific Medical Sciences 6.3 (2022): 119-126.


Copyright: © 2022 Malerba Mario., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Acceptance rate30%
Acceptance to publication20-30 days
Impact Factor1.403

Indexed In

News and Events

  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is May 30, 2024.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of "Best Article of the Issue"
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.

Contact US