Value of D-dimer in predicting various clinical outcomes following community-acquired pneumonia: A network meta-analysis

Background: Whether high D-dimer level before treatment has any impact on poor outcomes in patients with community-associated pneumonia (CAP) remains unclear. Therefore, we conducted the first meta-analysis focusing specifically on prognostic value of high D-dimer level before treatment in CAP patients. Methods: Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center were searched up to the end of March 2021. Randomized clinical trials (RCT) and observational studies were included to demonstrate the association between the level of D-dimer and clinical outcomes. Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation. Data were analyzed using STATA 14.0 to complete meta and network analysis. Main outcomes and measures: Besides d-dimer levels in CAP patients with poor outcomes, we also analyzed proportion of patients with or without poor outcomes correctly classified by the d-dimer levels as being at high or low risk. The poor outcome includes severe CAP, death, pulmonary embolism (PE) and invasive mechanical ventilators. Results: 32 studies with a total of 9,593 patients were eventually included. Pooled effect size (ES) suggested that d-dimer level was significantly higher in severe CAP patients than non-severe CAP patients with great heterogeneity (SMD = 1.21 95%CI 0.87–1.56, I2 = 86.8% p = 0.000). D-dimer level was significantly elevated in non-survivors compared to survivors with CAP (SMD = 1.22 95%CI 0.67–1.77, I2 = 85.1% p = 0.000). Prognostic value of d-dimer for pulmonary embolism (PE) was proved by hierarchical summary receiver operating characteristic curve (HSROC) with good summary sensitivity (0.74, 95%CI, 0.50–0.89) and summary specificity (0.82, 95%CI, 0.41–0.97). Network meta-analysis suggested that there was a significant elevation of d-dimer levels in CAP patients with poor outcome than general CAP patients but d-dimer levels weren’t significantly different among poor outcomes. Conclusion: The prognostic ability of d-dimer among patients with CAP appeared to be good at correctly identifying high-risk populations of poor outcomes, suggesting potential for clinical utility in patients with CAP.