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D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit

Year 2025, Volume: 9 Issue: 1, 17 - 23, 21.04.2025

Avsar Zerman , Cihan Aydin , Nermin Zerman

Abstract

Purpose: In this retrospective cohort study, evaluating the role of the D-dimer/fibrinogen ratio in predicting the in-hospital mortality rate of COVID-19 regardless of the presence of comorbidities was aimed.

Materials and Methods: This retrospective cohort study included patients admitted to the intensive care unit. The demographic data of the patients (sex, age, body mass index, comorbidities), their prognostic clinical scores, laboratory results, and need for and duration of invasive mechanical ventilation (IMV) were recorded.

Results: The rates of chronic renal diseases, acute renal failure, cardiac diseases, and severe sepsis were significantly higher in the exitus group. It was found that lower levels of lymphocytes were associated with increased mortality. Furthermore, neutrophil counts and the neutrophil to lymphocyte ratio (NLR) were associated with increased mortality. A higher D-dimer/fibrinogen ratio (DDFR) was a predictor of mortality but not a predictor of the duration of hospitalization in the ICU.

Conclusion: DDFR has a potential impact in anticipating mortality rates in COVID-19 patients.

Keywords

COVID-19 blood coagulation innate inflammatory response mortality rate

References

  • 1. Rostami M, Mansouritorghabeh H. D-dimer level in COVID-19 infection: a systematic review. Expert Rev Hematol. 2020;13(11):1265-1275.
  • 2. Malik P, Patel U, Mehta D, et al. Biomarkers and outcomes of COVID-19 hospitalizations: systematic review and meta-analysis. BMJ Evid Based Med. 2021;26(3):107-108.
  • 3. Qeadan F, Tingey B, Gu LY, Packard AH, Erdei E, Saeed AI. Prognostic Values of Serum Ferritin and D-Dimer Trajectory in Patients with COVID-19. Viruses. 2021;13(3):419.
  • 4. Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020;69(12):1181-1189.
  • 5. Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021;113(1):45-57.
  • 6. Ciceri F, Beretta L, Scandroglio AM et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit. Care Resus. 2020;22(2):95-97.
  • 7. Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: a novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin. Chim. Acta 2020;507:167-173.
  • 8. Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17(1):46-64.
  • 9. Aydin C, Yıldız BP, Hattatoğlu DG. D-dimer/Fibrinogen ratio and recurrent exacerbations might have a potential impact to predict 90-day mortality in patients with COPD exacerbation. Malawi Med J. 2021;33(4): 276-280.
  • 10. Du WN, Zhang Y, Yu Y, et al. D-dimer levels is associated with severe COVID-19 infections: A meta-analysis. Int J Clin Pract. 2021;75(8):e14031.
  • 11. Miltiades A, Houck PJ, Monteleone M, et al. Insights into Fibrinogen-Mediated COVID-19 Hypercoagubility in Critically Ill Patients. J Neurosurg Anesthesiol. 2022;34(1):136-140.
  • 12. 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.
  • 13. Zhao TJ, Yang QK, Tan CY, Bi LD, Li J, Miao ZL. Prognostic value of D-dimer/fibrinogen ratio in the adverse outcomes of patients hospitalized for heart failure. Biomark Med. 2020;14(18):1733-1745.
  • 14. Murat S, Murat B, Dural M, Mert GO, Cavusoglu Y. Prognostic value of D-dimer/fibrinogen ratio on in-hospital outcomes of patients with heart failure and COVID-19. BiomarkMed. 2021;15(16):1519-1528.
  • 15. Sungono V, Hariyanto H, Soesilo TEB, et al. Cohort study of the APACHE II score and mortality for different types of intensive care unit patients. Postgrad Med J. 2022;98(1166):914-918.
  • 16. Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit Care Med. 2009;37(5):1649-1654.
  • 17. Fleiss N, Polin RA. Sequential organ failure assessment scores to predict outcomes: from adults to neonates. Curr Opin Pediatr. 2023;35(2):218-222.
  • 18. Jain S, Iverson LM. Glasgow Coma Scale. In: StatPearls. Treasure Island: America.. https://www.ncbi.nlm.nih.gov/books/NBK 513298/ Accessed date 07 December, 2024.
  • 19. Eryilmaz-Eren E, Ture Z, Kilinç-Toker A, Korkmaz S, Çelik İ. The course of COVID-19 in patients with hematological malignancies and risk factors affecting mortality: A cross-sectional study. Hematol Transfus Cell Ther. 2024;46(1):3-7.
  • 20. Vardavas CI, Mathioudakis AG, Nikitara K, et al. Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2: a systematic review and meta-analysis of European cohort studies. Eur Respir Rev. 2022;31(166):220098.
  • 21. Menditto A, Protic O, Di Rosa M, Bonfigli AR, Lattanzio F, Antonicelli R. Admission high-sensitivity cardiac troponin levels as a prognostic indicator for in-hospital mortality rates in the elderly and very elderly COVID-19 patients. Arch Gerontol Geriatr. 2023;104:104822.
  • 22. Finfer S, Venkatesh B, Hotchkiss RS, Sasson SC. Lymphopenia in sepsis-an acquired immunodeficiency? Immunol Cell Biol. 2023;101(6):535-544.
  • 23. Geraili Z, Hajian-Tilaki K, Bayani M, et al. Evaluation of Time-Varying Biomarkers in Mortality Outcome in COVID-19: an Application of Extended Cox Regression Model. Acta Inform Med. 2022;30(4): 295-301.
  • 24. Ergenc Z, Ergenc H, Araç S, et al. Predictors of disease severity, clinical course, and therapeutic outcome in COVID-19 patients: our experience with 1,700 patients. Eur Rev Med Pharmacol Sci. 2022;26(21): 8180-8187.
  • 25. Elouadani M, Konzi C, Addi Y, et al. C-Reactive Protein, Ferritin, and Procalcitonin in 300 Moroccan Patients with COVID-19. Clin Lab. 2022;68(10).
  • 26. Zhan H, Chen H, Liu C, et al. Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression. Clin Appl Thromb Hemost. 2021;27:1-10.
  • 27. Qeadan F, Tingey B, Gu LY, Packard AH, Erdei E, Saeed AI. Prognostic Values of Serum Ferritin and D-Dimer Trajectory in Patients with COVID-19. Viruses. 2021;13(3):419.
  • 28. D'Ardes D, Boccatonda A, Cocco G, et al. Impaired coagulation, liver dysfunction, and COVID-19: Discovering an intriguing relationship. World J Gastroenterol. 2022;28(11):1102-1112.
  • 29. Moiseiwitsch N, Zwennes N, Szlam F, Sniecinski R, Brown A. COVID-19 patient fibrinogen produces dense clots with altered polymerization kinetics, partially explained by increased sialic acid. J Thromb Haemost. 2022;20(12):2909-2920.
  • 30. Bivona G, Agnello L, Ciaccio M. Biomarkers for Prognosis and Treatment Response in COVID-19 Patients. Ann Lab Med. 2021;41(6):540-548.
  • 31. Bester J, Matshailwe C, Pretorius E. Simultaneous presence of hypercoagulation and increased clot lysis time due to IL-1β, IL-6 and IL-8. Cytokine. 2018;110:237-242.

Yoğun Bakım Ünitesinde Yatan COVID-19 Hastalarında Mortalitenin Belirgin Bir Belirleyicisi Olarak D-Dimer/Fibrinojen Oranı

Year 2025, Volume: 9 Issue: 1, 17 - 23, 21.04.2025

Avsar Zerman , Cihan Aydin , Nermin Zerman

Abstract

Amaç: Bu retrospektif kohort çalışmada komorbidite varlığı üzerinden herhangi bir kısıtlama olmaksızın D-dimer/fibrinojen oranının COVID-19'da bir belirleyici olarak değerlendirilmesi amaçlandı.

Araçlar ve Yöntem: Yoğun bakım ünitesine kabul edilen hastalarla retrospektif kohort çalışması yapıldı. Demografik veriler (cinsiyet, yaş, vücut kitle indeksi, komorbiditeler), prognostik klinik skorlar, sıralı organ yetmezliği değerlendirme (SOFA) skoru ve Glasgow Koma Skalası (GKS) skorları, Yoğun bakımda yatan hastaların laboratuvar sonuçları ve invazif mekanik ventilasyon (İMV) ihtiyacı ve süresi kaydedildi.

Bulgular: Kronik böbrek hastalıkları, akut böbrek yetmezliği, kalp hastalıkları ve şiddetli sepsis, çıkış grubunda anlamlı olarak daha yüksekti. Daha düşük lenfosit seviyelerinin artan ölüm oranıyla ilişkili olduğu bulunmuştur. Ayrıca nötrofil/lenfosit oranı (NLR) ve nötrofiller artan mortaliteyle ilişkiliydi. Daha yüksek D-dimer/fibrinojen oranı (DDFR) mortalite için bir risk faktörüydü, ancak yoğun bakım ünitesinde yatış süresi için bir risk faktörü değildi.

Sonuç: DDFR'nin, COVID-19'da hastane içi mortaliteyi öngörmede potansiyel bir etkisi vardır.

Keywords

COVID-19 doğuştan gelen inflamatuar yanıt kan pıhtılaşması ölüm oranı

References

  • 1. Rostami M, Mansouritorghabeh H. D-dimer level in COVID-19 infection: a systematic review. Expert Rev Hematol. 2020;13(11):1265-1275.
  • 2. Malik P, Patel U, Mehta D, et al. Biomarkers and outcomes of COVID-19 hospitalizations: systematic review and meta-analysis. BMJ Evid Based Med. 2021;26(3):107-108.
  • 3. Qeadan F, Tingey B, Gu LY, Packard AH, Erdei E, Saeed AI. Prognostic Values of Serum Ferritin and D-Dimer Trajectory in Patients with COVID-19. Viruses. 2021;13(3):419.
  • 4. Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020;69(12):1181-1189.
  • 5. Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021;113(1):45-57.
  • 6. Ciceri F, Beretta L, Scandroglio AM et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit. Care Resus. 2020;22(2):95-97.
  • 7. Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: a novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin. Chim. Acta 2020;507:167-173.
  • 8. Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17(1):46-64.
  • 9. Aydin C, Yıldız BP, Hattatoğlu DG. D-dimer/Fibrinogen ratio and recurrent exacerbations might have a potential impact to predict 90-day mortality in patients with COPD exacerbation. Malawi Med J. 2021;33(4): 276-280.
  • 10. Du WN, Zhang Y, Yu Y, et al. D-dimer levels is associated with severe COVID-19 infections: A meta-analysis. Int J Clin Pract. 2021;75(8):e14031.
  • 11. Miltiades A, Houck PJ, Monteleone M, et al. Insights into Fibrinogen-Mediated COVID-19 Hypercoagubility in Critically Ill Patients. J Neurosurg Anesthesiol. 2022;34(1):136-140.
  • 12. 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.
  • 13. Zhao TJ, Yang QK, Tan CY, Bi LD, Li J, Miao ZL. Prognostic value of D-dimer/fibrinogen ratio in the adverse outcomes of patients hospitalized for heart failure. Biomark Med. 2020;14(18):1733-1745.
  • 14. Murat S, Murat B, Dural M, Mert GO, Cavusoglu Y. Prognostic value of D-dimer/fibrinogen ratio on in-hospital outcomes of patients with heart failure and COVID-19. BiomarkMed. 2021;15(16):1519-1528.
  • 15. Sungono V, Hariyanto H, Soesilo TEB, et al. Cohort study of the APACHE II score and mortality for different types of intensive care unit patients. Postgrad Med J. 2022;98(1166):914-918.
  • 16. Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit Care Med. 2009;37(5):1649-1654.
  • 17. Fleiss N, Polin RA. Sequential organ failure assessment scores to predict outcomes: from adults to neonates. Curr Opin Pediatr. 2023;35(2):218-222.
  • 18. Jain S, Iverson LM. Glasgow Coma Scale. In: StatPearls. Treasure Island: America.. https://www.ncbi.nlm.nih.gov/books/NBK 513298/ Accessed date 07 December, 2024.
  • 19. Eryilmaz-Eren E, Ture Z, Kilinç-Toker A, Korkmaz S, Çelik İ. The course of COVID-19 in patients with hematological malignancies and risk factors affecting mortality: A cross-sectional study. Hematol Transfus Cell Ther. 2024;46(1):3-7.
  • 20. Vardavas CI, Mathioudakis AG, Nikitara K, et al. Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2: a systematic review and meta-analysis of European cohort studies. Eur Respir Rev. 2022;31(166):220098.
  • 21. Menditto A, Protic O, Di Rosa M, Bonfigli AR, Lattanzio F, Antonicelli R. Admission high-sensitivity cardiac troponin levels as a prognostic indicator for in-hospital mortality rates in the elderly and very elderly COVID-19 patients. Arch Gerontol Geriatr. 2023;104:104822.
  • 22. Finfer S, Venkatesh B, Hotchkiss RS, Sasson SC. Lymphopenia in sepsis-an acquired immunodeficiency? Immunol Cell Biol. 2023;101(6):535-544.
  • 23. Geraili Z, Hajian-Tilaki K, Bayani M, et al. Evaluation of Time-Varying Biomarkers in Mortality Outcome in COVID-19: an Application of Extended Cox Regression Model. Acta Inform Med. 2022;30(4): 295-301.
  • 24. Ergenc Z, Ergenc H, Araç S, et al. Predictors of disease severity, clinical course, and therapeutic outcome in COVID-19 patients: our experience with 1,700 patients. Eur Rev Med Pharmacol Sci. 2022;26(21): 8180-8187.
  • 25. Elouadani M, Konzi C, Addi Y, et al. C-Reactive Protein, Ferritin, and Procalcitonin in 300 Moroccan Patients with COVID-19. Clin Lab. 2022;68(10).
  • 26. Zhan H, Chen H, Liu C, et al. Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression. Clin Appl Thromb Hemost. 2021;27:1-10.
  • 27. Qeadan F, Tingey B, Gu LY, Packard AH, Erdei E, Saeed AI. Prognostic Values of Serum Ferritin and D-Dimer Trajectory in Patients with COVID-19. Viruses. 2021;13(3):419.
  • 28. D'Ardes D, Boccatonda A, Cocco G, et al. Impaired coagulation, liver dysfunction, and COVID-19: Discovering an intriguing relationship. World J Gastroenterol. 2022;28(11):1102-1112.
  • 29. Moiseiwitsch N, Zwennes N, Szlam F, Sniecinski R, Brown A. COVID-19 patient fibrinogen produces dense clots with altered polymerization kinetics, partially explained by increased sialic acid. J Thromb Haemost. 2022;20(12):2909-2920.
  • 30. Bivona G, Agnello L, Ciaccio M. Biomarkers for Prognosis and Treatment Response in COVID-19 Patients. Ann Lab Med. 2021;41(6):540-548.
  • 31. Bester J, Matshailwe C, Pretorius E. Simultaneous presence of hypercoagulation and increased clot lysis time due to IL-1β, IL-6 and IL-8. Cytokine. 2018;110:237-242.
There are 31 citations in total.

Details

Primary Language English
Subjects Chest Diseases
Journal Section Original Articles
Authors

Avsar Zerman 0000-0003-0957-0766

Cihan Aydin 0000-0002-1789-0172

Nermin Zerman 0000-0002-1304-3224

Early Pub Date April 16, 2025
Publication Date April 21, 2025
Published in Issue Year 2025 Volume: 9 Issue: 1

Cite

APA Zerman, A., Aydin, C., & Zerman, N. (2025). D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit. Ahi Evran Medical Journal, 9(1), 17-23. https://doi.org/10.46332/aemj.1352549
AMA Zerman A, Aydin C, Zerman N. D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit. Ahi Evran Med J. April 2025;9(1):17-23. doi:10.46332/aemj.1352549
Chicago Zerman, Avsar, Cihan Aydin, and Nermin Zerman. “D-Dimer/Fibrinogen Ratio As a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit”. Ahi Evran Medical Journal 9, no. 1 (April 2025): 17-23. https://doi.org/10.46332/aemj.1352549.
EndNote Zerman A, Aydin C, Zerman N (April 1, 2025) D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit. Ahi Evran Medical Journal 9 1 17–23.
IEEE A. Zerman, C. Aydin, and N. Zerman, “D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit”, Ahi Evran Med J, vol. 9, no. 1, pp. 17–23, 2025, doi: 10.46332/aemj.1352549.
ISNAD Zerman, Avsar et al. “D-Dimer/Fibrinogen Ratio As a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit”. Ahi Evran Medical Journal 9/1 (April 2025), 17-23. https://doi.org/10.46332/aemj.1352549.
JAMA Zerman A, Aydin C, Zerman N. D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit. Ahi Evran Med J. 2025;9:17–23.
MLA Zerman, Avsar et al. “D-Dimer/Fibrinogen Ratio As a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit”. Ahi Evran Medical Journal, vol. 9, no. 1, 2025, pp. 17-23, doi:10.46332/aemj.1352549.
Vancouver Zerman A, Aydin C, Zerman N. D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit. Ahi Evran Med J. 2025;9(1):17-23.
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