The Etiopathogenesis of Thrombotic Events in COVID-19

Züleyha Yıldız Yümsek; Aysun Hacışevki

doi:10.59124/guhes.1818908

The Etiopathogenesis of Thrombotic Events in COVID-19

Abstract

Deep vein thrombosis, pulmonary embolism and peripheral artery thrombosis are among the most important complications of COVID-19. SARS-CoV-2 has been identified as a single-stranded RNA virus that enters cells by binding to angiotensin-converting enzyme 2, found in lung alveoli, cardiac myocytes, and vascular endothelial cells. The virus can survive on contaminated surfaces for up to 24-72 hours. In addition, transmission occurs after inhalation of viral particles from contaminated surfaces and their entry into the respiratory tract. SARS-CoV-2 is often associated with a cytokine storm, a hypercoagulable state, and the induction of marked autoimmune reactions. ACE receptors are also found in the human nasal epithelium, alveolar and gastrointestinal systems (small intestinal cells), as well as in the heart and kidneys; therefore, the pathological effects of infection are commonly observed in these areas. This multitrophic virus can cause multiple organ failure, particularly in the lungs, heart, and kidneys in severe cases. In this review we aim to investigate the pathophysiological mechanisms of thrombosis observed in COVID-19. In this context, studies on identifying prognostic markers as well as predictors of bleeding and thrombosis and selecting agents that will improve coagulation management will be beneficial in disease course and treatment.

Keywords

Supporting Institution

No financial support was received for this study.

Ethical Statement

Ethics committee approval was deemed unnecessary for this study, as open access sources were utilized; however, the study was conducted in accordance with ethical principles.

References

Arachchillage, D. J., Rajakaruna, I., Scott, I., Gaspar, M., Odho, Z., Banya, W., et al. (2022). Impact of major bleeding and thrombosis on 180-day survival in patients with severe COVID-19 supported with veno-venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study. Br J Haematol, 196(3), 566-576.https://doi:10.1111/bjh.17870
Asakura, H. (2014). Classifying types of disseminated intravascular coagulation: clinical and animal models. J Intensive Care, 2(1), 20.https://doi:10.1186/2052-0492-2-20
Bikdeli, B., Madhavan, M. V., Jimenez, D., Chuich, T., Dreyfus, I., Driggin, E., et al. (2020). 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, 75(23), 2950-2973.https://doi:10.1016/j.jacc.2020.04.031
Bosmann, M. (2021). Complement control for COVID-19. Sci Immunol, 6(59).https://doi:10.1126/sciimmunol.abj1014
Chaudhary, R., Garg, J., Houghton, D. E., Murad, M. H., Kondur, A., Chaudhary, R., et al. (2021). Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients. Mayo Clin Proc Innov Qual Outcomes, 5(2), 388-402.https://doi:10.1016/j.mayocpiqo.2021.01.009
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395(10223), 507-513.https://doi:10.1016/s0140-6736(20)30211-7
Connors, J. M., & Levy, J. H. (2020). COVID-19 and its implications for thrombosis and anticoagulation. Blood, 135(23), 2033-2040.https://doi:10.1182/blood.2020006000
Dunkelberger, J. R., & Song, W. C. (2010). Complement and its role in innate and adaptive immune responses. Cell Res, 20(1), 34-50.https://doi:10.1038/cr.2009.139

Fajgenbaum, D. C., & June, C. H. (2020). Cytokine Storm. N Engl J Med, 383(23), 2255-2273.https://doi:10.1056/NEJMra2026131
Frantzeskaki, F., Armaganidis, A., & Orfanos, S. E. (2017). Immunothrombosis in Acute Respiratory Distress Syndrome: Cross Talks between Inflammation and Coagulation. Respiration, 93(3), 212-225.https://doi:10.1159/000453002
Giannis, D., Ziogas, I. A., & Gianni, P. (2020). Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol, 127, 104362.https://doi:10.1016/j.jcv.2020.104362
Gómez-Mesa, J. E., Galindo-Coral, S., Montes, M. C., & Muñoz Martin, A. J. (2021). Thrombosis and Coagulopathy in COVID-19. Curr Probl Cardiol, 46(3), 100742.https://doi:10.1016/j.cpcardiol.2020.100742
Goudarzi, E., Yousefimoghaddam, F., Ramandi, A., & Khaheshi, I. (2022). COVID-19 and peripheral artery thrombosis: a mini review. Current problems in cardiology, 47(10), 100992.
Guan, W. J., Ni, Z. Y., Hu, Y., Liang, W. H., Ou, C. Q., He, J. X., et al. (2020). Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med, 382(18), 1708-1720.https://doi:10.1056/NEJMoa2002032
Hacışevki, A., & Baba, B. (2020). An Overview of Vitamins and Minerals in the Prevention of COVID-19 Infection. Gazi Medical Journal, 31. doi:http://dx.doi.org/10.12996/gmj.2020.123
Halpert, G., & Shoenfeld, Y. (2020). SARS-CoV-2, the autoimmune virus. Autoimmun Rev, 19(12), 102695.https://doi:10.1016/j.autrev.2020.102695
Hamming, I., Timens, W., Bulthuis, M. L., Lely, A. T., Navis, G., & van Goor, H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol, 203(2), 631-637.https://doi:10.1002/path.1570
Hanff, T. C., Mohareb, A. M., Giri, J., Cohen, J. B., & Chirinos, J. A. (2020). Thrombosis in COVID-19. Am J Hematol, 95(12), 1578-1589.https://doi:10.1002/ajh.25982
Heesterbeek, D. A., Bardoel, B. W., Parsons, E. S., Bennett, I., Ruyken, M., Doorduijn, D. J., et al. (2019). Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. Embo j, 38(4).https://doi:10.15252/embj.201899852
Hu, D. (2017). Role of Anti-inflammatory Cytokines IL-35 and IL-37 in Asthma. Inflammation, 40(2), 697-707.https://doi:10.1007/s10753-016-0480-6
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506.https://doi:10.1016/s0140-6736(20)30183-5
Iba, T., Levy, J. H., Levi, M., Connors, J. M., & Thachil, J. (2020). Coagulopathy of Coronavirus Disease 2019. Crit Care Med, 48(9), 1358-1364.https://doi:10.1097/ccm.0000000000004458
Klok, F. A., Kruip, M., van der Meer, N. J. M., Arbous, M. S., Gommers, D., Kant, K. M., et al. (2020). Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res, 191, 145-147.https://doi:10.1016/j.thromres.2020.04.013
Kowalewski, M., Fina, D., Słomka, A., Raffa, G. M., Martucci, G., Lo Coco, V., et al. (2020). COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review. Crit Care, 24(1), 205.https://doi:10.1186/s13054-020-02925-3
LaRovere, K. L., Riggs, B. J., Poussaint, T. Y., Young, C. C., Newhams, M. M., Maamari, M., et al. (2021). Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome. JAMA Neurol, 78(5), 536-547.https://doi:10.1001/jamaneurol.2021.0504
Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., et al. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood, 124(2), 188-195.https://doi:10.1182/blood-2014-05-552729
Lee, M. H., Perl, D. P., Nair, G., Li, W., Maric, D., Murray, H., et al. (2021). Microvascular Injury in the Brains of Patients with Covid-19. N Engl J Med, 384(5), 481-483.https://doi:10.1056/NEJMc2033369
Levi, M., Thachil, J., Iba, T., & Levy, J. H. (2020). Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol, 7(6), e438-e440.https://doi:10.1016/s2352-3026(20)30145-9
Liu, Y., Yang, Y., Zhang, C., Huang, F., Wang, F., Yuan, J., et al. (2020). Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci, 63(3), 364-374.https://doi:10.1007/s11427-020-1643-8
Lodigiani, C., Iapichino, G., Carenzo, L., Cecconi, M., Ferrazzi, P., Sebastian, T., et al. (2020). Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res, 191, 9-14.https://doi:10.1016/j.thromres.2020.04.024
Lupu, F., Keshari, R.S., Lambris, J.D., & Coggeshall, K.M. (2014). Crosstalk between the coagulation and complement systems in sepsis. Thromb Res,133(0 1), 28-31. https://doi: 10.1016/j.thromres.2014.03.014.
Meinhardt, J., Radke, J., Dittmayer, C., Franz, J., Thomas, C., Mothes, R., et al. (2021). Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci, 24(2), 168-175.https://doi:10.1038/s41593-020-00758-5
Millar, J. E., Fanning, J. P., McDonald, C. I., McAuley, D. F., & Fraser, J. F. (2016). The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Crit Care, 20(1), 387.https://doi:10.1186/s13054-016-1570-4
Panigada, M., Bottino, N., Tagliabue, P., Grasselli, G., Novembrino, C., Chantarangkul, V., et al. (2020). Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost, 18(7), 1738-1742.https://doi:10.1111/jth.14850
Poissy, J., Goutay, J., Caplan, M., Parmentier, E., Duburcq, T., Lassalle, F., et al. (2020). Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation, 142(2), 184-186.https://doi:10.1161/circulationaha.120.047430
Puelles, V. G., Lütgehetmann, M., Lindenmeyer, M. T., Sperhake, J. P., Wong, M. N., Allweiss, L., et al. (2020). Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med, 383(6), 590-592.https://doi:10.1056/NEJMc2011400
Rhea, E. M., Logsdon, A. F., Hansen, K. M., Williams, L. M., Reed, M. J., Baumann, K. K., et al. (2021). The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat Neurosci, 24(3), 368-378.https://doi:10.1038/s41593-020-00771-8
Schmidt, M., Hajage, D., Lebreton, G., Monsel, A., Voiriot, G., Levy, D., et al. (2020). Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study. Lancet Respir Med, 8(11), 1121-1131.https://doi:10.1016/s2213-2600(20)30328-3
Spyropoulos, A. C., Levy, J. H., Ageno, W., Connors, J. M., Hunt, B. J., Iba, T., et al. (2020). 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, 18(8), 1859-1865.https://doi:10.1111/jth.14929
Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., et al. (2020). SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine, 26(5), 681-687.https://doi:10.1038/s41591-020-0868-6
Takahashi, T., Ellingson, M. K., Wong, P., Israelow, B., Lucas, C., Klein, J., et al. (2020). Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature, 588(7837), 315-320.https://doi:10.1038/s41586-020-2700-3
Tang, N., Bai, H., Chen, X., Gong, J., Li, D., & Sun, Z. (2020). Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost, 18(5), 1094-1099.https://doi:10.1111/jth.14817
Tang, N., Li, D., Wang, X., & Sun, Z. (2020). Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost, 18(4), 844-847.https://doi:10.1111/jth.14768
Thachil, J., Tang, N., Gando, S., Falanga, A., Cattaneo, M., Levi, M., et al. (2020). ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost, 18(5), 1023-1026.https://doi:10.1111/jth.14810
Vlaar, A. P. J., de Bruin, S., Busch, M., Timmermans, S., van Zeggeren, I. E., Koning, R., et al. (2020). Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol, 2(12), e764-e773.https://doi:10.1016/s2665-9913(20)30341-6
Walport, M. J. (2001). Complement. First of two parts. N Engl J Med, 344(14), 1058-1066.https://doi:10.1056/nejm200104053441406
Wang, D., Li, R., Wang, J., Jiang, Q., Gao, C., Yang, J., et al. (2020). Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis, 20(1), 519.https://doi:10.1186/s12879-020-05242-w
Wautier, J. L., & Wautier, M. P. (2023). Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review. Int J Mol Sci, 24(11).https://doi:10.3390/ijms24119647
Zhao, J., Yang, Y., Huang, H., Li, D., Gu, D., Lu, X., et al. (2021). Relationship Between the ABO Blood Group and the Coronavirus Disease 2019 (COVID-19) Susceptibility. Clin Infect Dis, 73(2), 328-331.https://doi:10.1093/cid/ciaa1150
Zhao, J., Zhang, G., Cui, W., & Tian, B. (2020). [Progress of neutrophil extracellular traps in airway inflammation of acute lung injury/acute respiratory distress syndrome: Review]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 36(7), 664-670.

Details

Primary Language

English

Subjects

Primary Health Care

Journal Section

Review

Authors

Züleyha Yıldız Yümsek
0000-0002-4897-4870
Türkiye

Aysun Hacışevki ^*
0000-0002-3844-5772
Türkiye

Publication Date

April 30, 2026

Submission Date

November 6, 2025

Acceptance Date

December 2, 2025

Published in Issue

Year 2026 Volume: 8 Number: 1

DOI

https://doi.org/10.59124/guhes.1818908

IZ

https://izlik.org/JA84SE52ZT

Cite

RIS / Bibtex

APA

Yıldız Yümsek, Z., & Hacışevki, A. (2026). The Etiopathogenesis of Thrombotic Events in COVID-19. Journal of Gazi University Health Sciences Institute, 8(1), 1-10. https://doi.org/10.59124/guhes.1818908

AMA

1.Yıldız Yümsek Z, Hacışevki A. The Etiopathogenesis of Thrombotic Events in COVID-19. GUHES. 2026;8(1):1-10. doi:10.59124/guhes.1818908

Chicago

Yıldız Yümsek, Züleyha, and Aysun Hacışevki. 2026. “The Etiopathogenesis of Thrombotic Events in COVID-19”. Journal of Gazi University Health Sciences Institute 8 (1): 1-10. https://doi.org/10.59124/guhes.1818908.

EndNote

Yıldız Yümsek Z, Hacışevki A (April 1, 2026) The Etiopathogenesis of Thrombotic Events in COVID-19. Journal of Gazi University Health Sciences Institute 8 1 1–10.

IEEE

[1]Z. Yıldız Yümsek and A. Hacışevki, “The Etiopathogenesis of Thrombotic Events in COVID-19”, GUHES, vol. 8, no. 1, pp. 1–10, Apr. 2026, doi: 10.59124/guhes.1818908.

ISNAD

Yıldız Yümsek, Züleyha - Hacışevki, Aysun. “The Etiopathogenesis of Thrombotic Events in COVID-19”. Journal of Gazi University Health Sciences Institute 8/1 (April 1, 2026): 1-10. https://doi.org/10.59124/guhes.1818908.

JAMA

1.Yıldız Yümsek Z, Hacışevki A. The Etiopathogenesis of Thrombotic Events in COVID-19. GUHES. 2026;8:1–10.

MLA

Yıldız Yümsek, Züleyha, and Aysun Hacışevki. “The Etiopathogenesis of Thrombotic Events in COVID-19”. Journal of Gazi University Health Sciences Institute, vol. 8, no. 1, Apr. 2026, pp. 1-10, doi:10.59124/guhes.1818908.

Vancouver

1.Züleyha Yıldız Yümsek, Aysun Hacışevki. The Etiopathogenesis of Thrombotic Events in COVID-19. GUHES. 2026 Apr. 1;8(1):1-10. doi:10.59124/guhes.1818908