The clinical and prognostic role of changes in parameters of the hemostasis system and C-reactive protein in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19)

Authors

DOI:

https://doi.org/10.14739/2310-1237.2023.1.274921

Keywords:

COVID-19, viral infection, thrombotic complications, diagnosis, hemostasis, C-reactive protein, risk factors, prognosis

Abstract

Aim. The purpose of our work was to find out the clinical and prognostic role of changes in hemostasis parameters and C-reactive protein (CRP) in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19).

Materials and methods. 211 oxygen-dependent patients with COVID-19 were examined. To assess the prognostic role of changes in hemostasis parameters and CRP, patients were divided into groups: I group – 94 patients who recovered, II group – 117 patients who died. Subgroups: II-A subgroup – 35 patients with thrombotic complications and II-B subgroup – 82 patients without these complications. All patients were examined and received treatment according to the normative documents in force at the relevant time.

Results. The frequency of thrombotic complications in oxygen-dependent patients with COVID-19 was 16.6 %, among which the most common were pulmonary embolism (6.6 %), myocardial infarction (6.2 %), and ischemic stroke (3.2 %). Lifetime diagnosis of thrombotic complications took place on the 18th [16.0; 24.0] day of illness in 45.9 % of cases. Deathtime diagnosis of thrombotic complications took place on the 24th [20.0; 28.0] day of illness in 54.1 % of cases. Lifetime pulmonary artery thromboembolism was diagnosed less frequently than ischemic stroke (p = 0.002) and myocardial infarction (p = 0.02).

With the development of oxygen dependence and admission to the intensive care unit on the 9th [8.0; 11.0] day of illness, changes in the hemostasis system were characterized as prothrombotic with an increase above the reference values of fibrinogen and D-dimer in patients of all groups. CRP in patients with fatal outcomes of the disease, regardless of the development of thrombotic complications, was higher (p < 0.05) than in patients who subsequently recovered, and was accordingly in patients of the I group – 67.65 [41.20; 139.95] mg/l, in the II-A group – 122.2 [61.2; 178.0] mg/l, and in patients of the II-B group – 109.8 [56.3; 180.0] mg/l.

In the dynamics of complex treatment after 5–7 days, the level of fibrinogen, D-dimer and CRP had a diagnostic value in predicting the further development of thrombotic complications. With an increase in the level of fibrinogen >4.6 g/l (AUC = 0.600, p = 0.042), D-dimer >2.1 μg/ml (AUC = 0.704, p = 0.001) and CRP >89.3 mg/l (AUC = 0.720, p < 0.001) the probability of developing thrombotic complications was significant.

Conclusions. In dynamics of complex treatment of oxygen-dependent patients after 5–7 days, the levels of fibrinogen, D-dimer and C-reactive protein had consistent diagnostic value in predicting further development of thrombotic complications. Increased fibrinogen >4.6 g/l, D-dimer >2.1 μg/ml, and CRP >89.3 mg/l were important for predicting the risk of developing thrombotic complications.

Author Biographies

V. V. Cherkaskyi, Zaporizhzhia State Medical University, Ukraine

асистент каф. інфекційних хвороб

O. V. Riabokon, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Infectious Diseases

Yu. Yu. Riabokon, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Children Infectious Diseases

References

Muralidar, S., Ambi, S. V., Sekaran, S., & Krishnan, U. M. (2020). The emergence of COVID-19 as a global pandemic: Understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2. Biochimie, 179, 85-100. https://doi.org/10.1016/j.biochi.2020.09.018

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506. https://doi.org/10.1016/S0140-6736(20)30183-5

Synowiec, A., Szczepański, A., Barreto-Duran, E., Lie, L. K., & Pyrc, K. (2021). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection. Clinical microbiology reviews, 34(2), e00133-20. https://doi.org/10.1128/CMR.00133-20

Zhang, S., Liu, Y., Wang, X., Yang, L., Li, H., Wang, Y., Liu, M., Zhao, X., Xie, Y., Yang, Y., Zhang, S., Fan, Z., Dong, J., Yuan, Z., Ding, Z., Zhang, Y., & Hu, L. (2020). SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. Journal of hematology & oncology, 13(1), 120. https://doi.org/10.1186/s13045-020-00954-7

Merad, M., & Martin, J. C. (2020). Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature reviews. Immunology, 20(6), 355-362. https://doi.org/10.1038/s41577-020-0331-4

Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., Manson, J. J., & HLH Across Speciality Collaboration, UK (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 395(10229), 1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0

Petrilli, C. M., Jones, S. A., Yang, J., Rajagopalan, H., O’Donnell, L., Chernyak, Y., Tobin, K. A., Cerfolio, R. J., Francois, F., & Horwitz, L. I. (2020). Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ (Clinical research ed.), 369, m1966. https://doi.org/10.1136/bmj.m1966

Liu, F., Li, L., Xu, M., Wu, J., Luo, D., Zhu, Y., Li, B., Song, X., & Zhou, X. (2020). Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. Journal of clinical virology, 127, 104370. https://doi.org/10.1016/j.jcv.2020.104370

Ruan, Q., Yang, K., Wang, W., Jiang, L., & Song, J. (2020). Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive care medicine, 46(5), 846-848. https://doi.org/10.1007/s00134-020-05991-x

Smadja, D. M., Mentzer, S. J., Fontenay, M., Laffan, M. A., Ackermann, M., Helms, J., Jonigk, D., Chocron, R., Pier, G. B., Gendron, N., Pons, S., Diehl, J. L., Margadant, C., Guerin, C., Huijbers, E. J. M., Philippe, A., Chapuis, N., Nowak-Sliwinska, P., Karagiannidis, C., Sanchez, O., … Griffioen, A. W. (2021). COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects. Angiogenesis, 24(4), 755-788. https://doi.org/10.1007/s10456-021-09805-6

Connors, J. M., & Levy, J. H. (2020). COVID-19 and its implications for thrombosis and anticoagulation. Blood, 135(23), 2033-2040. https://doi.org/10.1182/blood.2020006000

Singhania, N., Bansal, S., Nimmatoori, D. P., Ejaz, A. A., McCullough, P. A., & Singhania, G. (2020). Current Overview on Hypercoagulability in COVID-19. American journal of cardiovascular drugs : drugs, devices, and other interventions, 20(5), 393-403. https://doi.org/10.1007/s40256-020-00431-z

Levi, M., & Iba, T. (2021). COVID-19 coagulopathy: is it disseminated intravascular coagulation?. Internal and emergency medicine, 16(2), 309-312. https://doi.org/10.1007/s11739-020-02601-y

van der Linden, J., Almskog, L., Liliequist, A., Grip, J., Fux, T., Rysz, S., Ågren, A., Oldner, A., & Ståhlberg, M. (2020). Thromboembolism, Hypercoagulopathy, and Antiphospholipid Antibodies in Critically Ill Coronavirus Disease 2019 Patients: A Before and After Study of Enhanced Anticoagulation. Critical care explorations, 2(12), e0308. https://doi.org/10.1097/CCE.0000000000000308

Becker, R. C. (2020). COVID-19 update: Covid-19-associated coagulopathy. Journal of thrombosis and thrombolysis, 50(1), 54-67. https://doi.org/10.1007/s11239-020-02134-3

Colling, M. E., & Kanthi, Y. (2020). COVID-19-associated coagulopathy: An exploration of mechanisms. Vascular medicine, 25(5), 471-478. https://doi.org/10.1177/1358863X20932640

Peyvandi, F., Artoni, A., Novembrino, C., Aliberti, S., Panigada, M., Boscarino, M., Gualtierotti, R., Rossi, F., Palla, R., Martinelli, I., Grasselli, G., Blasi, F., & Tripodi, A. (2021). Hemostatic alterations in COVID-19. Haematologica, 106(5), 1472-1475. https://doi.org/10.3324/haematol.2020.262634

Ribes, A., Vardon-Bounes, F., Mémier, V., Poette, M., Au-Duong, J., Garcia, C., Minville, V., Sié, P., Bura-Rivière, A., Voisin, S., & Payrastre, B. (2020). Thromboembolic events and Covid-19. Advances in biological regulation, 77, 100735. https://doi.org/10.1016/j.jbior.2020.100735

Middeldorp, S., Coppens, M., van Haaps, T. F., Foppen, M., Vlaar, A. P., Müller, M. C. A., Bouman, C. C. S., Beenen, L. F. M., Kootte, R. S., Heijmans, J., Smits, L. P., Bonta, P. I., & van Es, N. (2020). Incidence of venous thromboembolism in hospitalized patients with COVID-19. Journal of thrombosis and haemostasis : JTH, 18(8), 1995-2002. https://doi.org/10.1111/jth.14888

Malas, M. B., Naazie, I. N., Elsayed, N., Mathlouthi, A., Marmor, R., & Clary, B. (2020). Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine, 29, 100639. https://doi.org/10.1016/j.eclinm.2020.100639

Lopes, R. D., de Barros E Silva, P. G. M., Furtado, R. H. M., Macedo, A. V. S., Bronhara, B., Damiani, L. P., Barbosa, L. M., de Aveiro Morata, J., Ramacciotti, E., de Aquino Martins, P., de Oliveira, A. L., Nunes, V. S., Ritt, L. E. F., Rocha, A. T., Tramujas, L., Santos, S. V., Diaz, D. R. A., Viana, L. S., Melro, L. M. G., de Alcântara Chaud, M. S., … ACTION Coalition COVID-19 Brazil IV Investigators (2021). Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet, 397(10291), 2253-2263. https://doi.org/10.1016/S0140-6736(21)01203-4

Jenner, W. J., Kanji, R., Mirsadraee, S., Gue, Y. X., Price, S., Prasad, S., & Gorog, D. A. (2021). Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review. Journal of thrombosis and thrombolysis, 51(3), 595-607. https://doi.org/10.1007/s11239-021-02394-7

Nahum, J., Morichau-Beauchant, T., Daviaud, F., Echegut, P., Fichet, J., Maillet, J. M., & Thierry, S. (2020). Venous Thrombosis Among Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). JAMA network open, 3(5), e2010478. https://doi.org/10.1001/jamanetworkopen.2020.10478

Rey, J. R., Caro-Codón, J., Poveda Pineda, D., Merino, J. L., Iniesta, Á. M., López-Sendón, J. L., & investigadores CARD-COVID (2020). Complicaciones arteriales trombóticas en pacientes hospitalizados con COVID-19 [Arterial thrombotic complications in hospitalized patients with COVID-19]. Revista espanola de cardiologia, 73(9), 769-771. https://doi.org/10.1016/j.recesp.2020.05.013

Tan, Y. K., Goh, C., Leow, A. S. T., Tambyah, P. A., Ang, A., Yap, E. S., Tu, T. M., Sharma, V. K., Yeo, L. L. L., Chan, B. P. L., & Tan, B. Y. Q. (2020). COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature. Journal of thrombosis and thrombolysis, 50(3), 587-595. https://doi.org/10.1007/s11239-020-02228-y

Levi, M., Thachil, J., Iba, T., & Levy, J. H. (2020). Coagulation abnormalities and thrombosis in patients with COVID-19. The Lancet. Haematology, 7(6), e438-e440. https://doi.org/10.1016/S2352-3026(20)30145-9

Thachil, J., Cushman, M., & Srivastava, A. (2020). A proposal for staging COVID-19 coagulopathy. Research and practice in thrombosis and haemostasis, 4(5), 731-736. https://doi.org/10.1002/rth2.12372

Helms, J., Severac, F., Merdji, H., Anglés-Cano, E., & Meziani, F. (2020). Prothrombotic phenotype in COVID-19 severe patients. Intensive care medicine, 46(7), 1502-1503. https://doi.org/10.1007/s00134-020-06082-7

Thachil, J., Tang, N., Gando, S., Falanga, A., Cattaneo, M., Levi, M., Clark, C., & Iba, T. (2020). ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of thrombosis and haemostasis : JTH, 18(5), 1023-1026. https://doi.org/10.1111/jth.14810

Shah, S., Shah, K., Patel, S. B., Patel, F. S., Osman, M., Velagapudi, P., Turagam, M. K., Lakkireddy, D., & Garg, J. (2020). Elevated D-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. Cardiology in review, 28(6), 295-302. https://doi.org/10.1097/CRD.0000000000000330

Kwee, R. M., Adams, H. J. A., & Kwee, T. C. (2021). Pulmonary embolism in patients with COVID-19 and value of D-dimer assessment: a meta-analysis. European radiology, 31(11), 8168-8186. https://doi.org/10.1007/s00330-021-08003-8

Chocron, R., Duceau, B., Gendron, N., Ezzouhairi, N., Khider, L., Trimaille, A., Goudot, G., Weizman, O., Alsac, J. M., Pommier, T., Bory, O., Cellier, J., Philippe, A., Geneste, L., Ben Abdallah, I., Panagides, V., El Batti, S., Marsou, W., Juvin, P., Deney, A., … Critical COVID-19 France investigators (2021). D-dimer at hospital admission for COVID-19 are associated with in-hospital mortality, independent of venous thromboembolism: Insights from a French multicenter cohort study. Archives of cardiovascular diseases, 114(5), 381-393. https://doi.org/10.1016/j.acvd.2021.02.003

Smilowitz, N. R., Kunichoff, D., Garshick, M., Shah, B., Pillinger, M., Hochman, J. S., & Berger, J. S. (2021). C-reactive protein and clinical outcomes in patients with COVID-19. European heart journal, 42(23), 2270-2279. https://doi.org/10.1093/eurheartj/ehaa1103

Ministry of Health of Ukraine. (2021, January 7). Pro zatverdzhennia Zmin do Standartiv medychnoi dopomohy “Koronavirusna khvoroba (COVID-19)”. Nakaz MOZ Ukrainy No. 10 [On the approval of the Amendments to the Medical Care Standards “Coronavirus Disease (COVID-19)” (No. 10)]. URL: https://zakon.rada.gov.ua/rada/show/v0010282-21?lang=en#Text

Ministry of Health of Ukraine. (2020, April 2). Protokol nadannia medychnoi dopomohy dlia likuvannia koronavirusnoi khvoroby (COVID-19). Nakaz MOZ Ukrainy No. 762 [Protocol for the provision of medical assistance for the treatment of the coronavirus disease (COVID-19) (No. 762)]. https://zakon.rada.gov.ua/rada/show/v0762282-20#Text

Ministry of Health of Ukraine. (2020, March 28). Orhanizatsiia nadannia medychnoi dopomohy khvorym na koronavirusnu khvorobu (COVID-19). Nakaz MOZ Ukrainy No. 722 [Organization of medical care for patients with coronavirus disease (COVID-19) (No. 722)]. https://zakon.rada.gov.ua/rada/show/v0722282-20?lang=en#Text

Riabokon, O. V., Tumanska, L. M., Cherkaskyi, V. V., & Riabokon, Yu. Yu. (2021). Clinical and pathomorphological analysis of deaths from COVID-19 in 2020. Pathologia, 18(3), 269-277. https://doi.org/10.14739/2310-1237.2021.3.242247

Longchamp, A., Longchamp, J., Manzocchi-Besson, S., Whiting, L., Haller, C., Jeanneret, S., Godio, M., Garcia Martinez, J. J., Bonjour, T., Caillat, M., Maitre, G., Thaler, J. M., Pantet, R., Donner, V., Dumoulin, A., Emonet, S., Greub, G., Friolet, R., Robert-Ebadi, H., Righini, M., … Delaloye, J. (2020). Venous thromboembolism in critically Ill patients with COVID-19: Results of a screening study for deep vein thrombosis. Research and practice in thrombosis and haemostasis, 4(5), 842-847. https://doi.org/10.1002/rth2.12376

Lodigiani, C., Iapichino, G., Carenzo, L., Cecconi, M., Ferrazzi, P., Sebastian, T., Kucher, N., Studt, J. D., Sacco, C., Bertuzzi, A., Sandri, M. T., Barco, S., & Humanitas COVID-19 Task Force (2020). Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thrombosis research, 191, 9-14. https://doi.org/10.1016/j.thromres.2020.04.024

Kollias, A., Kyriakoulis, K. G., Lagou, S., Kontopantelis, E., Stergiou, G. S., & Syrigos, K. (2021). Venous thromboembolism in COVID-19: A systematic review and meta-analysis. Vascular medicine, 26(4), 415-425. https://doi.org/10.1177/1358863X21995566

Mansory, E. M., Srigunapalan, S., & Lazo-Langner, A. (2021). Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis. TH open : companion journal to thrombosis and haemostasis, 5(3), e286-e294. https://doi.org/10.1055/s-0041-1730967

Nopp, S., Moik, F., Jilma, B., Pabinger, I., & Ay, C. (2020). Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis. Research and practice in thrombosis and haemostasis, 4(7), 1178-1191. https://doi.org/10.1002/rth2.12439

Voicu, S., Bonnin, P., Stépanian, A., Chousterman, B. G., Le Gall, A., Malissin, I., Deye, N., Siguret, V., Mebazaa, A., & Mégarbane, B. (2020). High Prevalence of Deep Vein Thrombosis in Mechanically Ventilated COVID-19 Patients. Journal of the American College of Cardiology, 76(4), 480-482. https://doi.org/10.1016/j.jacc.2020.05.053

Wichmann, D., Sperhake, J. P., Lütgehetmann, M., Steurer, S., Edler, C., Heinemann, A., Heinrich, F., Mushumba, H., Kniep, I., Schröder, A. S., Burdelski, C., de Heer, G., Nierhaus, A., Frings, D., Pfefferle, S., Becker, H., Bredereke-Wiedling, H., de Weerth, A., Paschen, H. R., Sheikhzadeh-Eggers, S., … Kluge, S. (2020). Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Annals of internal medicine, 173(4), 268-277. https://doi.org/10.7326/M20-2003

Deng, H., Yan, X., & Yuan, L. (2021). Human genetic basis of coronavirus disease 2019. Signal transduction and targeted therapy, 6(1), 344. https://doi.org/10.1038/s41392-021-00736-8

Carter-Timofte, M. E., Jørgensen, S. E., Freytag, M. R., Thomsen, M. M., Brinck Andersen, N. S., Al-Mousawi, A., Hait, A. S., & Mogensen, T. H. (2020). Deciphering the Role of Host Genetics in Susceptibility to Severe COVID-19. Frontiers in immunology, 11, 1606. https://doi.org/10.3389/fimmu.2020.01606

Berger, J. S., Kunichoff, D., Adhikari, S., Ahuja, T., Amoroso, N., Aphinyanaphongs, Y., Cao, M., Goldenberg, R., Hindenburg, A., Horowitz, J., Parnia, S., Petrilli, C., Reynolds, H., Simon, E., Slater, J., Yaghi, S., Yuriditsky, E., Hochman, J., & Horwitz, L. I. (2020). Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19. Arteriosclerosis, thrombosis, and vascular biology, 40(10), 2539-2547. https://doi.org/10.1161/ATVBAHA.120.314872

Downloads

Published

2023-04-28

How to Cite

1.
Cherkaskyi VV, Riabokon OV, Riabokon YY. The clinical and prognostic role of changes in parameters of the hemostasis system and C-reactive protein in the development of thrombotic complications in oxygen-dependent patients with coronavirus disease (COVID-19). Pathologia [Internet]. 2023Apr.28 [cited 2024Nov.14];20(1):27-35. Available from: http://pat.zsmu.edu.ua/article/view/274921

Issue

Section

Original research