Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases

Wan Nur Maisarah Wan Rosli; Tharmini Ravi; Long Chiau Ming; Hanis Hanum Zulkifly

Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases

Abstract

Background: Thromboembolic (TE) complications are associated with the severity of the infection and are no less of a disease that contributes to the fatality of critically ill patients infected with COVID-19. Objective: This study aimed to investigate the prevalence of TE complications, in-hospital mortality, and risk factors among ICU patients (stage 3, 4, 5) infected with COVID-19. Methodology: In this retrospective single-center cross-sectional study, 106 severe patients referred to intensive care units (ICUs) due to COVID-19 between February 2021 and December 2022 were included. All patients received a thromboprophylaxis agent. Results: Mean (SD) age 49.81(13.27), 50.9% were male, 68.9% Malays, mean (SD) (2-12) days of ICU admission with the most coexisting comorbidities being hypertension (44.3%), diabetes mellitus (33%), and obesity (60.3%). Of 106 patients, 51 (41.9%) developed pulmonary embolism (PE) and 27.5% died despite adequate thromboprophylaxis. In total, 51 (41.9%) developed TE event during their ICU admission. Significantly higher proportions of COVID-19 patients who developed complications of PE (77.8% vs 42%; p = 0.006) died. D-dimer, fibrinogen, white cell count (WCC), and troponin were significantly greater among those with TE events. Demographics, co-morbidities, other laboratory parameters and were similar in COVID- 19 patients with and without TE events. Conclusion: There is a high incidence of TE complications and in-hospital mortality in critically ill patients with COVID-19. A high level of D-dimer, fibrinogen, white cell count, and troponin were associated with in-hospital TE events. It is apparent that routine chemical thromboprophylaxis may not be sufficient to prevent TE complications in patients with severe COVID-19.

Keywords

References

[1] Medicine JHU. Covid-19 Johns Hopkins Coronavirus Resource Center 2022 [Available from: http://coronavirus.jhu.edu/].
[2] Ciotti M, Ciccozzi M, Terrinoni A, Jiang W-C, Wang C-B, Bernardini S. The COVID-19 pandemic. Crit Rev Clin Lab Sci. 2020;57(6):365-88. https://doi.org/10.1080/10408363.2020.1783198
[3] Russell L, Weihe S, Madsen EK, Hvas CL, Leistner JW, Michelsen J, et al. Thromboembolic and bleeding events in ICU patients with COVID-19: A nationwide, observational study. Acta Anaesthesiol Scand. 2023;67(1):76-85.
[4] Vaqar S, Graber M. Thromboembolic Event. 2019. https://doi.org/10.1111/aas.14157
[5] Ashorobi D, Ameer MA, Fernandez R. Thrombosis. StatPearls [Internet]. 2022.
[6] Boonyawat K, Chantrathammachart P, Numthavaj P, Nanthatanti N, Phusanti S, Phuphuakrat A, et al. Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis. Thromb J. 2020;18(1):1-12. https://doi.org/10.1186/s12959-020-00248-5
[7] Cuker A, Peyvandi F. COVID-19: Hypercoagulability. UpToDate Ed: Post TW Waltham, Massachusetts Cuker A Peyvandi F COVID-19: Hypercoagulability In UpToDate Post TW Waltham, Massachusetts Search in. 2021. https://doi.org/10.1097%2FSHK.0000000000001660
[8] Gomez-Mesa JE, Galindo-Coral S, Montes MC, Martin AJM. Thrombosis and Coagulopathy in COVID-19. Curr Probl Cardiol. 2021;46(3):100742. https://doi.org/10.1016/j.cpcardiol.2020.100742

[9] Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-98. https://doi.org/10.1007/s00134-020-06062-x
[10] Kruse JM, Magomedov A, Kurreck A, Münch FH, Koerner R, Kamhieh-Milz J, et al. Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis. Crit Care. 2020;24(1):1-10. https://doi.org/10.1186/s13054-020-03401-8
[11] Health Mo. Clinical Management of Confirmed COVID-19 Case in Adult [-]. -: -; 2020 [updated 3/11; cited 2020 3/11]. -; -: [Prophylaxis dose of anticoagulant]. Available from: https://covidlawlab.org/wp-content/uploads/2021/02/Malaysia_2020.11.03_Guidelines_Clinical-Management-of-Confirmed-COVID-19-Case-in-Adult_EN.pdf.
[12] Malaysia MoH. Prevention and Treatment of Venous Thromboembolism 2013. Available from: https://www.moh.gov.my/moh/attachments/9005.pdf.
[13] Klok F, Kruip M, Van der Meer N, Arbous M, Gommers D, Kant K, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-7. https://doi.org/10.1016/j.thromres.2020.04.013
[14] Nahum J, Morichau-Beauchant T, Daviaud F, Echegut P, Fichet J, Maillet J-M, et al. Venous thrombosis among critically ill patients with coronavirus disease 2019 (COVID-19). JAMA Netw Open. 2020;3(5):e2010478-e. https://doi.org/10.1001%2Fjamanetworkopen.2020.10478
[15] 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. https://doi.org/10.1111/jth.14830
[16] Hippensteel JA, Burnham EL, Jolley SE. Prevalence of venous thromboembolism in critically ill patients with COVID‐19. Br J Haematol. 2020;190(3):e134. https://doi.org/10.1111/bjh.16908
[17] Bellmunt-Montoya S, Riera C, Gil D, Rodríguez M, García-Reyes M, Martínez-Carnovale L, et al. COVID-19 infection in critically ill patients carries a high risk of venous thrombo-embolism. Eur J Vasc Endovasc Surg. 2021;61(4):628-34. https://doi.org/10.1016/j.ejvs.2020.12.015
[18] Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation. 2020;142(2):184-6. https://doi.org/10.1161/circulationaha.120.047430
[19] Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D‐dimer levels on admission to predict in‐hospital mortality in patients with Covid‐19. J Thromb Haemost. 2020;18(6):1324-9. https://doi.org/10.1111/jth.14859
[20] Lee Y, Jehangir Q, Li P, Gudimella D, Mahale P, Lin C-H, et al. Venous thromboembolism in COVID-19 patients and prediction model: a multicenter cohort study. BMC Infect Dis. 2022;22(1):1-14. https://doi.org/10.1186/s12879-022-07421-3
[21] Hansen E-S, Rinde FB, Edvardsen MS, Hindberg K, Latysheva N, Aukrust P, et al. Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism. Thromb Res. 2021;208:121-6. https://doi.org/10.1016/j.thromres.2021.10.020
[22] Evensen LH, Folsom AR, Pankow JS, Hansen JB, Allison MA, Cushman M, et al. Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: The Multi‐Ethnic Study of Atherosclerosis. J Thromb Haemost. 2021;19(7):1718-28. https://doi.org/10.1111%2Fjth.15315
[23] Yuriditsky E, Horowitz JM, Merchan C, Ahuja T, Brosnahan SB, McVoy L, et al. Thromboelastography profiles of critically ill patients with coronavirus disease 2019. Crit Care Med. 2020. https://doi.org/10.1097%2FCCM.0000000000004471
[24] Sui J, Noubouossie DF, Gandotra S, Cao L. Elevated plasma fibrinogen is associated with excessive inflammation and disease severity in COVID-19 patients. Front Cell Infect Microbiol. 2021;11:734005. https://doi.org/10.3389/fcimb.2021.734005
[25] Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19. J Med Viroл. 2020;92(7):791-6. https://doi.org/10.1002/jmv.25770
[26] Klok F, Kruip M, Van der Meer N, Arbous M, Gommers D, Kant K, 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. https://doi.org/10.1016/j.thromres.2020.04.041
[27] Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MC, et al. Incidence of venous thromboembolism in hospitalized patients with COVID‐19. J Thromb Haemost. 2020;18(8):1995-2002. https://doi.org/10.1111/jth.14888
[28] Thomas W, Varley J, Johnston A, Symington E, Robinson M, Sheares K, et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res. 2020;191:76-7. https://doi.org/10.1016%2Fj.thromres.2020.04.028
[29] Maatman TK, Jalali F, Feizpour C, Anthony Douglas I, McGuire SP, Kinnaman G, et al. Routine venous thromboembolism prophylaxis may be inadequate in the hypercoagulable state of severe coronavirus disease 2019. Crit Care Med. 2020. https://doi.org/10.1097/ccm.0000000000004466

Details

Primary Language

English

Subjects

Clinical Pharmacy and Pharmacy Practice

Journal Section

Clinical Research

Authors

Wan Nur Maisarah Wan Rosli This is me
0009-0007-7843-7172
Malaysia

Tharmini Ravi This is me
0009-0002-6005-8813
Malaysia

Long Chiau Ming
0000-0002-6971-1383
Malaysia

Hanis Hanum Zulkifly ^* This is me
0000-0002-8474-7317
Malaysia

Publication Date

June 28, 2025

Submission Date

August 24, 2023

Acceptance Date

March 21, 2024

Published in Issue

Year 2024 Volume: 28 Number: 4

IZ

https://izlik.org/JA46RR36RU

Cite

RIS / Bibtex

APA

Wan Rosli, W. N. M., Ravi, T., Ming, L. C., & Zulkifly, H. H. (2025). Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases. Journal of Research in Pharmacy, 28(4), 1244-1252. https://izlik.org/JA46RR36RU

AMA

1.Wan Rosli WNM, Ravi T, Ming LC, Zulkifly HH. Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases. J. Res. Pharm. 2025;28(4):1244-1252. https://izlik.org/JA46RR36RU

Chicago

Wan Rosli, Wan Nur Maisarah, Tharmini Ravi, Long Chiau Ming, and Hanis Hanum Zulkifly. 2025. “Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 Stage 3-5 ICU Cases”. Journal of Research in Pharmacy 28 (4): 1244-52. https://izlik.org/JA46RR36RU.

EndNote

Wan Rosli WNM, Ravi T, Ming LC, Zulkifly HH (July 1, 2025) Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases. Journal of Research in Pharmacy 28 4 1244–1252.

IEEE

[1]W. N. M. Wan Rosli, T. Ravi, L. C. Ming, and H. H. Zulkifly, “Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases”, J. Res. Pharm., vol. 28, no. 4, pp. 1244–1252, July 2025, [Online]. Available: https://izlik.org/JA46RR36RU

ISNAD

Wan Rosli, Wan Nur Maisarah - Ravi, Tharmini - Ming, Long Chiau - Zulkifly, Hanis Hanum. “Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 Stage 3-5 ICU Cases”. Journal of Research in Pharmacy 28/4 (July 1, 2025): 1244-1252. https://izlik.org/JA46RR36RU.

JAMA

1.Wan Rosli WNM, Ravi T, Ming LC, Zulkifly HH. Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases. J. Res. Pharm. 2025;28:1244–1252.

MLA

Wan Rosli, Wan Nur Maisarah, et al. “Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 Stage 3-5 ICU Cases”. Journal of Research in Pharmacy, vol. 28, no. 4, July 2025, pp. 1244-52, https://izlik.org/JA46RR36RU.

Vancouver

1.Wan Nur Maisarah Wan Rosli, Tharmini Ravi, Long Chiau Ming, Hanis Hanum Zulkifly. Assessing Thromboembolic Complications and In- Hospital Mortality and Clinical Factors Affecting Thromboembolic Complications in COVID-19 stage 3-5 ICU cases. J. Res. Pharm. [Internet]. 2025 Jul. 1;28(4):1244-52. Available from: https://izlik.org/JA46RR36RU