D-Dimer, a Biomarker for Diagnosis and Prognosis Assessment of COVID-19
Coagulopathy [1] and increased levels of antiphospholipid antibodies [2] are more prevalent in critically ill-COVID-19 patients and may predispose patients to both arterial and venous thrombotic diseases, due to blood circulation stasis, endothelial dysfunction, platelet activation, and excessive inflammation.
Editorial
Coagulopathy [1] and increased levels of antiphospholipid antibodies [2] are more prevalent in critically ill-COVID-19 patients and may predispose patients to both arterial and venous thrombotic diseases, due to blood circulation stasis, endothelial dysfunction, platelet activation, and excessive inflammation. D-dimer, a marker of fibrinolysis and a proxy for ongoing thrombosis is the sensitive change in coagulation parameters in COVID-19, whereas it has low specificity for the detection of venous thromboembolism [3]. A retrospective cohort study in France demonstrated that D-dimer levels at baseline significantly higher in patients with deep venous thrombosis (DVT) (p < 0.001), whereas the positive predictive values for venous thromboembolism (VTE) for baseline D-dimer levels that were equal to 1.0µg/mL or more and more than 3µg/mL were 44% and 67%, respectively and the negative predictive values for baseline D-dimer levels that was less than 1.0 µg/mL for VTE and pulmonary embolism (PE) were 90%and 98%, respectively [4]. VTE risk was predicted by elevated D-dimer concentrations of more than 1.0µg/mL [4]. In another prospective study of 165 consecutive hospitalized-non-intensive-care-unit-COVID- 19-related pneumonia patients with D-dimer levels of more than 1,000ng/mL and complete compression doppler ultrasonography screening revealed that the D-dimer levels were higher in diagnosed-DVT patients, compared to other patients (4,527ng/mL vs. 2,050ng/mL; p<0.001) [5]. He, et al. demonstrated that a D-dimer level of 2.025mg/L was the suitable probability cutoff or a prognosis of death, whereas male gender, advanced age, dyspnea, and some underlying diseases were the influencing factors D-dimer levels impacting COVID-19 prognosis [6], whereas Poudel, et al. demonstrated that D-dimer level of 1.5µg/mL on hospital admission is the proper cutoff level for predicting the mortality in COVID-19 patients [7]. Zhan, et al. conducted a meta-analysis and meta- regression on diagnostic value of D-dimer levels in COVID-19 patients and revealed that the specificity of the prognostic performance of D-dimer levels for the severity, mortality, and VTE in COVID-19 were 71%(95% CI: 64%-77%), 83%(95% CI: 77%-87%) and 60%(95% CI: 60%-60%), respectively, and the pooled sensitivity were 77%(95% CI: 73%-80%), 75%(95% CI: 65%-82%) and 90%(95% CI: 90%-90%) respectively [8]. In conclusion, D-dimer level testing is not useful for the diagnosis of PE due to low positive predictive values of increased D-dimer levels. The high levels of D-dimer in COVID-19 patients do not definitely making the diagnosis of DVT, but can be used for screening VTE-related-COVID-19. Reduction in D-dimer levels may correlate with COVID-19 clinical improvement.
References
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Devreese KMJ, Linskens EA, Benoit D, Peperstraete H (2020) Antiphospholipid antibodies in patients with COVID-19 : a relevant observation. J Thromb Haemost 18 (9): 2191-2201.
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Righini M, Perrier A, De Moerloose P, Bounameaux H (2008) D-dimer for venous thromboembolism diagnosis : 20 years later. J Thromb Haemost 6(7): 1059-1071.
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Artifoni M, Danic G, Gautier G (2020) Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors. J Thromb Thrombolysis 50 (1): 211-216.
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Rodriguez DP, Cervilla-Munnoz E, Ortega OL (2020) Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res 192: 23-26.
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He X, Yao F, Chen J, Wang Y, Fang X, et al. (2021) The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients. Scientific Reports 11: 1830.
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Poudel A, Poudel Y, Adhikari A, Aryal BB, Dangol D, et al. (2021) 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 16(8): e0256744.
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Zhan H, Chen H, Liu C, Chen L, Yan S, et al. (2021) Diagnostic value of D-dimer in COVID-19: a meta-analysis and meta-regression. Clinical and Applied Thrombosis/ Hemostasis 27: 1-10.
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