D-dimer: a biomarker for predicting disease severity and outcome in hospitalized children with COVID-19 and post COVID multisystem inflammatory syndrome

Nazish Saqlain; Attia Bari; Aimen C.; Masood Sadiq

doi:10.18203/2349-3291.ijcp20231837

Authors

Nazish Saqlain Department of Hematology and Transfusion Medicine, UCHS, The Children’s Hospital, Lahore, Pakistan
Attia Bari Department of Pediatric Medicine, UCHS, The Children’s Hospital, Lahore, Pakistan
Aimen C. Department of Pediatric Medicine, UCHS, The Children’s Hospital, Lahore, Pakistan
Masood Sadiq Department of Pediatric Cardiology, UCHS, The Children's Hospital, Lahore, Pakistan

DOI:

https://doi.org/10.18203/2349-3291.ijcp20231837

Keywords:

COVID-19, SARS-CoV-2, D-Dimer, Children, Acute respiratory disease

Abstract

Background: COVID-19 has presented with varied signs and symptoms with raised inflammatory markers among which D-dimers have been highlighted right from the beginning. Objectives were to analyze the relationship of D-dimers with the disease severity and outcome of children with COVID-19 and MIS-C in a developing country.

Methods: It was a retrospective study conducted at a pediatric tertiary care hospital from March 2020 to November 2021. Clinical and laboratory details of confirmed COVID-19 and post COVID-19 MIS-C cases were recorded. D-dimer testing was performed using Chemiluminescence technique. It’s relation with disease severity and predictive role for in-hospital mortality were established by using ROC curves and cut-off values were calculated by using SPSS-24.

Results: Of 272 children, 182 were of COVID-19 and 90 were of MIS-C. The mean age for COVID-19 and MIS-C patients was 5.4±4.8 years and 6.4±3.5 years respectively. Mild disease was seen in 33% cases while 17.6% were critical and 56.2% had some under lying comorbidity at presentation. Mean D-dimers were significantly higher in children with severe disease, who required ICU admission and non-survivors as compared to those with mild or moderate disease, not requiring ICU care and survivors, both in COVID-19 and MIS-C patients. ROC curve identified D-dimer value of ≥4.58 µg/ml (AUC=0.845) for COVID-19 cases and ≥4.73 µg/ml (AUC=0.682) for MIS-C patients as predictive of mortality.

Conclusions: Raised D-dimer level is a reliable predictor of disease severity and outcome in children with COVID-19 and MIS-C. The D-dimer value of 4.58 µg/ml for COVID-19 cases and 4.73µg/ml for MIS-C patients was found to be the cut-off levels for predicting mortality

Metrics

Metrics Loading ...

References

Zheng J. SARS-coV-2: An emerging coronavirus that causes a global threat. Int J Biol Sci. 2020;16(10):1678-85.

Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020;1.

Sun K, Chen J, Viboud C. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study. Lancet Digit Heal. 2020;10.

Ji L-N, Chao S, Wang Y-J, Li X-J, Mu X-D, Lin M-G, et al. Clinical features of pediatric patients with COVID-19: a report of two family cluster cases. World J Pediatr. 2020;1-2.

Sadiq M, Aziz OA, Kazmi U, Hyder N, Sarwar M, Sultana N, et al. Multisystem inflammatory syndrome associated with COVID-19 in children in Pakistan The. Lancet child Adolesc Heal. Elsevier Ltd; 2020;4642(20):19-20.

Michael B, Benoit SW, Helena M, Oliveira S De, Chin W, Benoit J, et al. Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review. Clin Biochem. 2020;81(1):1-8.

Yun H, Sun Z, Wu J, Tang A, Hu M, Xiang Z. Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients. Clin Chim Acta. 2020;507:94-7.

Saleh M, Alkofide A, Alshammari A, Siddiqui K, Owaidah T. Changes in Hematological , Clinical and Laboratory Parameters for Children with COVID-19 : Single-Center Experience. J Blood Med. 2021;819-26.

Yao Y, Cao J, Wang Q, Shi Q, Liu K, Luo Z, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: A case control study. J Intensive Care. J Intensive Care. 2020;8(1):1-11.

Rostami A, Sepidarkish M, Lee MMG, Riahi SM, Shiadeh MN, Esfandyari S, et al. SARS-CoV-2 seroprevalence worldwide : a systematic review and. Clin Microbiol Infect. 2021;27(3):331-40.

WHO. Clinical Management of COVID-19: Interim Guidance, 27 May 2020. World Health Organization. 2020. Available at: https://apps.who.int/iris/ bitstream/handle/10665/332196/WHO-2019-nCoV-clinical-2020.5-eng.pdf. Accessed on 25 March, 2023.

Saqlain N, Mazher N, Bari A, Ch. A, Farhan S, Ahmed N. Association of elevated D-dimers with severity and outcome of COVID-19 infection in children. Research and practice in Thrombosis and Haemostasis. 2021;5(SUPPL 2).

Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children. 2020;7(7):69.

Yasuhara J, Kuno T, Takagi H, Sumitomo N. Clinical characteristics of COVID-19 in children: A systematic review. Pediatr Pulmonol. 2020;55(10):2565-75.

Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, Tong S. Epidemiology of COVID-19 Among Children in China. Pediatrics. 2020;145(6):e20200702.

Castagnoli R, Votto M, Licari A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;1-10.

Zabeida A, Winikoff R, Pelland-Marcotte MC, Charlebois J, Sabapathy C. COVID-19-associated coagulopathy in children: A multicenter observational cohort study. Pediatr Blood Cancer. 2023;70(1):e30079.

Bansal A, Singh AD, Jain V, Aggarwal M, Gupta S, Padappayil RP, et al. The association of D-dimers with mortality, intensive care unit admission or acute respiratory distress syndrome in patients hospitalized with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Heart Lung. 2021;50(1):9-12.

Shoar S. D-dimer and poor clinical outcome in patients with COVID-19: lessons from meta-analysis of case-control studies. Heart Lung. 2021;50(2):298.

Nugroho J, Wardhana A, Maghfirah I, Mulia EPB, Rachmi DA, A'yun MQ, Septianda I. Relationship of D-dimer with severity and mortality in SARS-CoV-2 patients : A meta-analysis. Int J Lab Hematol. 2021;43(1):110-5.

Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infec Dis. 2020;95:304–7

Tang N, Li D, Wang X. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thrombosis Haemostasis. 2020;18:844-7.

Huang C, Wang Y, Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet . 2020;395:497-506.

Ozen M, Yilmaz A, Cakmak V, Beyoglu R, Oskay A, Seyit M, Senol H. D-Dimer as a potential biomarker for disease severity in COVID-19. Am J Emerg Med. 2021;40:55-9.

Al-Ghafry M, Vagrecha A, Malik M, Levine C, Uster E, Aygun B, et al. Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort. J Thromb Haemost. 2021;19(7):1764-70.

Poudel A, Poudel Y, Adhikari A, Aryal BB, Dangol D, Bajracharya T, et al. D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS one. 2021;16(8):e0256744.

Buonsenso D, Mariani F, Pierri L, Morello R, Yock-Corrales A, Del Aguila O, et al. Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study. Children. 2022;9:279.

McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, et al. Treatment of Multisystem Inflammatory Syndrome in Children. N Engl J Med. 2021;385:11-22.