The content of D-dimer and platelets as predictors of an unfavorable outcome in the critical course of COVID-19: a single-center

   Research Objective. The aim of this study is to comprehensively assess D-dimer and platelet (PLT) levels in patients with severe and critical COVID-19, analyze their correlation with the intensity of the inflammatory response and disease severity, and identify the days of stay in the intensive care unit (ICU) associated with the highest risk of unfavorable outcomes.

   Materials and Methods. A total of 70 individuals were examined: the study group included 50 COVID-19 patients (age 45,5 [32–48] years), and the control group consisted of 20 healthy volunteers (age 42,5 [34–47.5] years). The study group was further divided into two subgroups: severe course (Subgroup I, survivors, n = 30) and critical course (Subgroup II, deceased, n = 20). Venous blood levels of D-dimer, PLT, leukocytes (WBC), and C-reactive protein (CRP) were measured in COVID-19 patients on days 3, 5, 7, 10, and 16 of the disease, while the control group was assessed once. The respiratory index (RI) and its correlation with D-dimer and PLT levels were evaluated in the study group. Additionally, correlations between WBC/CRP and D-dimer/PLT levels were analyzed. Statistical analysis was performed using Student’s t-test, ANOVA, Spearman’s correlation, and ROC analysis.

   Results. Elevated D-dimer levels were observed, with peak values in the deceased subgroup on day 10 (2,36 ± 0,11 ng/mL; p < 0,001). At the same time point, Subgroup II exhibited the lowest PLT counts (107,05 ± 5.07 × 10⁹/L; p < 0,001). A significant correlation was found between high D-dimer levels and thrombocytopenia compared to elevated WBC and CRP levels, as well as between D-dimer/PLT and RI on days 7 and 10 in the deceased subgroup. ROC analysis identified optimal prognostic cut-off values for mortality: D-dimer >1,41 ng/mL and PLT <126,0 × 10⁹/L on day 7 of the disease.

   Conclusion. High D-dimer levels and thrombocytopenia in the setting of systemic inflammation indicate thromboinflammation and coagulopathy in critically ill COVID-19 patients, serving as unfavorable prognostic markers. A D-dimer level >1,41 ng/mL and PLT count <126,0 × 10⁹/L by day 7 of ICU admission may predict fatal outcomes in critical COVID-19 cases.

1. Barrett T.J., Bilaloglu S., Cornwell M. et al. Platelets contribute to disease severity in COVID-19. J Thromb Haemost. 2021. 19. 3139–3153. DOI: 10.1111/jth.15534.

2. Yao Y., Cao J., Wang Q. et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intensive Care. 2020. 8. 49. DOI: 10.1186/s40560-020-00466-z

3. Çelik O., Laloğlu E., Çelik N. The role of platelet large cell ratio in determining mortality in COVID-19 patients. Medicine (Baltimore). 2024. 103(18). 38033. DOI: 10.1097/MD.0000000000038033.

4. Tahmaz A., Keskin A.S., Kizilates F. A Prognostic Marker in COVID-19 Disease Severity and Mortality: D-Dimer/Platelet Ratio. Cureus. 2023. 15(5). 39580. DOI: 10.7759/cureus.39580.

5. Ackermann M., Verleden S.E., Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med. 2020. 383. 120–128. DOI: 10.1056/NEJMoa2015432.

6. Wool G.D., Miller J.L. The Impact of COVID-19 Disease on Platelets and Coagulation. Pathobiology. 2021. 88(1). 15-27. DOI: 10.1159/000512007.

7. Kostinov M.P., Zhang Chen, Khrapunova I.A. and others. The dynamics of platelet counts and D-dimer in vaccinated individuals with COVID-19 compared with those who were not immunized against this infection. Russian Journal of Immunology 2023. 26(4). 627-632. DOI: 10.46235/1028-7221-13983-TDC

8. Cekic D., Issever K., Genc A.C. et al. Association of C-reactive Protein/Albumin, Procalcitonin/Albumin, Platelet/Lymphocyte, and Lymphocyte/Monocyte Ratio with Mortality in Hospitalised COVID-19 Patients. J Coll Physicians Surg Pak. 2022. 32. 1191–1195. DOI: 10.29271/jcpsp.2022.09.1191

9. Rostami M., Mansouritorghabeh H. D-dimer level in COVID-19 infection : a systematic review. Expert Rev Hematol. 2020. 13. 1265–1275. DOI: 10.1080/17474086.2020.1831383.

10. Elkhalifa A.M. D-dimer as a predictive and prognostic marker among COVID-19 patients. Saudi Med J. 2022. 43(7). 723–729. DOI: 10.15537/smj.2022.43.7.20220213

11. Shahri M.K., Niazkar H.R., Rad F. COVID-19 and hematology findings based on the current evidences: a puzzle with many missing pieces. Int J Lab Hematol. 2021. 43. 160–168. DOI: 10.1111/ijlh.13412

12. Svetlitskaya O.I., Kanus I.I. Respiratory support for patients with acute lung injury. Surgery news. 2014. 22(4). 474-480.

13. Morozov S.P., Gombolevsky V.A., Chernina V.Yu. and others. Prediction of deaths in COVID-19 according to computed tomography of the chest organs. Tuberculosis and lung diseases. 2020. 98(6). 7-14. 10.21292/2075- DOI: 1230-2020-98-6-7-14.

14. Temporary guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Version 13 (14. 10. 2021).

15. Yamada T., Wakabayashi M., Yamaji T. et al. Value of leukocytosis and elevated C-reactive protein in predicting severe coronavirus 2019 (COVID-19) : A systematic review and meta-analysis. Clin Chim Acta. 2020. 509. 235–243. DOI: 10.1016/j.cca.2020.06.008

16. Ji P., Zhu J., Zhong Z. et al. Association of elevated inflammatory markers and severe COVID-19. Medicine (Baltimore). 2020. 99(47). 23315. DOI: 10.1097/MD.0000000000023315

17. Yang X., Yang Q., Wang Y. et al. Thrombocytopenia and its association with mortality in patients with COVID‐19. J Thromb Haemost. 2022(а). 18(6). 1469–1472. DOI: 10.1111/jth.14848

18. Yang Q., Gao J., Zeng X. et al. Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study. Front Med (Lausanne). 2022 (b). 9. 802412. DOI: 10.3389/fmed.2022.802412

19. Eslamifar Z., Behzadifard M., Zare Z. Investigation of homocysteine, D-dimer and platelet count levels as potential predictors of thrombosis risk in COVID-19 patients. Mol Cell Biochem. 2025. 480(1). 439-444. DOI: 10.1007/s11010-024-04967-5.