The Optimal Cutoff Value of D-dimer Levels to Predict in Hospital Mortality in Severe Cases of Coronavirus Disease 2019

Ngakan Ketut Wira Suastika; Ketut  Suega

doi:10.3889/oamjms.2021.7600

Authors

Ngakan Ketut Wira Suastika Department of Internal Medicine, Faculty of Medicine, Udayana University, Udayana University Hospital, Bali, Indonesia https://orcid.org/0000-0003-2306-101X
Ketut Suega Department of Internal Medicine, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7600

Keywords:

D-dimer, Mortality, Coronavirus disease 2019

Abstract

Introduction: Coronavirus disease 2019 (Covid-19) can cause coagulation parameters abnormalities such as an increase of D-dimer levels especially in severe cases. The purpose of this study is to determine the differences of D-dimer levels in severe cases of Covid-19 who survived and non-survived and determine the optimal cut-off value of D-dimer levels to predict in-hospital mortality.

Method: Data were obtained from confirmed Covid-19 patients who were treated from June to September 2020. The Mann-Whitney U test was used to determine differences of D-dimer levels in surviving and non-surviving patients. The optimal cut-off value and area under the curve (AUC) of the D-dimer level in predicting mortality were obtained by the receiver operating characteristic curve (ROC) method.

Results: A total of 80 patients were recruited in this study. Levels of D-dimer were significantly higher in non-surviving patients (median 3.346 mg/ml; minimum – maximum: 0.939 – 50.000 mg/ml) compared to surviving patients (median 1.201 mg/ml; minimum – maximum: 0.302 – 29.425 mg/ml), p = 0.012. D-dimer levels higher than 1.500 mg/ml are the optimal cut-off value for predicting mortality in severe cases of Covid-19 with a sensitivity of 80.0%; specificity of 64.3%; and area under the curve of 0.754 (95% CI 0.586 - 0.921; p = 0.010).

Conclusions: D-dimer levels can be used as a predictor of mortality in severe cases of Covid-19.

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References

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Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res. 2019;181:77-83. https://doi.org/10.1016/j.thromres.2019.07.013 PMid:31376606

Harper PL, Theakston E, Ahmed J, Ockelford P. D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly. Intern Med J. 2007;37(9):607-13. https://doi.org/10.1111/j.1445-5994.2007.01388.x PMid:17543005

Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: The Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. https://doi.org/10.1111/j.1538-7836.2010.04044.x PMid:20738765

Hess K, Grant PJ. Inflammation and thrombosis in diabetes. J Thromb Haemost. 2011;105(S06):S43-54. https://doi.org/10.1160/THS10-11-0739 PMid:21479339

Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989-94. https://doi.org/10.1111/jth.14578 PMid:31410983

Yu B, Li X, Chen J, Ouyang M, Zhang H, Zhao X, et al. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: A retrospective analysis. J Thromb Thrombolysis. 2020;50:548-57. https://doi.org10.1007/s11239-020-02171-y

World Health Organization. Coronavirus Disease (COVID-19) Outbreak. Emergencies Diseases. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019. [Last accessed on 2020 Sep 30].

Zhang L, Long Y, Xiao H, Yang J, Toulon P, Zhang Z. Use of D-dimer in oral anticoagulation therapy. Int J Lab Hem. 2018;40(5):503-7. https://doi.org/10.1111/ijlh.12864 PMid:29806239 DOI: https://doi.org/10.1111/ijlh.12864

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-7. https://doi.org/10.1111/jth.14768 PMid:32291954 DOI: https://doi.org/10.1111/jth.14768

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395(10299):1054-62. https://doi.org/10.1016/S0140-6736(20)30566-3 PMid:32171076 DOI: https://doi.org/10.1016/S0140-6736(20)30566-3

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 PMid:32306492 DOI: https://doi.org/10.1111/jth.14859

Yu HH, Qin C, Chen M, Wang W, Tian DS. D-dimer level is associated with the severity of COVID-19. Thromb Res. 2020;195:219-25. https://doi.org/10.1016/j.thromres.2020.07.047 PMid:32777639 DOI: https://doi.org/10.1016/j.thromres.2020.07.047

World Health Organization. Clinical Management of Severe Acute Respiratory Infection (SARI) when COVID-19 Disease is Suspected: Interim Guidance, 27 May 2020. Geneva: World Health Organization; 2020. DOI: https://doi.org/10.15557/PiMR.2020.0003

Han H, Yang L, Liu R, Liu F, Liu F, Wu KL, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58(7):1116-20. https://doi.org/10.1515/cclm-2020-0188 PMid:32172226 DOI: https://doi.org/10.1515/cclm-2020-0188

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5 PMid:31986264 DOI: https://doi.org/10.1016/S0140-6736(20)30183-5

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-9. https://doi.org/10.1111/jth.14817 PMid:32220112 DOI: https://doi.org/10.1111/jth.14817

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395(10223):507-13. https://doi.org/10.1016/S0140-6736(20)30211-7 PMid:32007143 DOI: https://doi.org/10.1016/S0140-6736(20)30211-7

Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18(5):1023-6. https://doi.org/10.1111/jth.14810 PMid:32338827 DOI: https://doi.org/10.1111/jth.14810

Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, Parra-Virto A, Toledano-Macías M, Toledo-Samaniego N, et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res. 2020;192:23-6. https://doi.org/10.1016/j.thromres.2020.05.018 PMid:32405101 DOI: https://doi.org/10.1016/j.thromres.2020.05.018

Long H, Nie L, Xiang X, Li H, Zhang X, Fu X, et al. D-Dimer and Prothrombin Time Are the Significant Indicators of Severe COVID-19 and Poor Prognosis. Biomed Res Int. 2020;2002:6159720. https://doi.org/10.1155/2020/6159720 PMid:32596339 DOI: https://doi.org/10.1155/2020/6159720

Wong JP, Viswanathan S, Wang M, Sun LQ, Clark GC, D’elia RV. Current and future developments in the treatment of virusinduced hypercytokinemia. Future Med Chem. 2017;9(2):169-78. https://doi.org/10.4155/fmc-2016-0181 PMid:28128003 DOI: https://doi.org/10.4155/fmc-2016-0181

Li XY, Du B, Wang YS, Kang HY, Wang F, Sun B, et al. The keypoints in treatment of the critical coronavirus disease 2019 patient (1). Chin J Resp Dis. 2020;43(4):273-277. https://doi.org/10.3760/cma.j.cn112147-20200222-00151 PMid:32087621

Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38-44. https://doi.org/10.1016/j.thromres.2016.11.007 PMid:7886531 DOI: https://doi.org/10.1016/j.thromres.2016.11.007

Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res. 2019;181:77-83. https://doi.org/10.1016/j.thromres.2019.07.013 PMid:31376606 DOI: https://doi.org/10.1016/j.thromres.2019.07.013

Harper PL, Theakston E, Ahmed J, Ockelford P. D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly. Intern Med J. 2007;37(9):607-13. https://doi.org/10.1111/j.1445-5994.2007.01388.x PMid:17543005 DOI: https://doi.org/10.1111/j.1445-5994.2007.01388.x

Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: The Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. https://doi.org/10.1111/j.1538-7836.2010.04044.x PMid:20738765 DOI: https://doi.org/10.1111/j.1538-7836.2010.04044.x

Hess K, Grant PJ. Inflammation and thrombosis in diabetes. J Thromb Haemost. 2011;105(S06):S43-54. https://doi.org/10.1160/THS10-11-0739 PMid:21479339 DOI: https://doi.org/10.1160/THS10-11-0739

Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989-94. https://doi.org/10.1111/jth.14578 PMid:31410983 DOI: https://doi.org/10.1111/jth.14578

Yu B, Li X, Chen J, Ouyang M, Zhang H, Zhao X, et al. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: A retrospective analysis. J Thromb Thrombolysis. 2020;50:548-57. https://doi.org10.1007/s11239-020-02171-y DOI: https://doi.org/10.1007/s11239-020-02171-y