Elevated D-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

Abstract

The 2019 novel coronavirus, declared a pandemic, has infected 2.6 million people as of April 27, 2020, and has resulted in the death of 181,938 people. D-dimer is an important prognostic tool, is often elevated in patients with severe coronavirus disease-19 (COVID-19) infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of D-dimer in COVID-19-infected patients. We searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission D-dimer levels in COVID-19 patients and its effect on mortality. Eighteen studies (16 retrospective and 2 prospective) with a total of 3682 patients met the inclusion criteria. The pooled weighted mean difference (WMD) demonstrated significantly elevated D-dimer levels in patients who died versus those who survived (WMD, 6.13 mg/L; 95% confidence interval [CI] 4.16-8.11; P < 0.001). Similarly, the pooled mean D-dimer levels were significantly elevated in patients with severe COVID-19 infection (WMD, 0.54 mg/L; 95% CI 0.28-0.80; P < 0.001). The risk of mortality was fourfold higher in patients with positive D-dimer versus negative D-dimer (risk ratio, 4.11; 95% CI, 2.48-6.84; P < 0.001) and the risk of developing severe disease was twofold higher in patients with positive D-dimer levels versus negative D-dimer (risk ratio, 2.04; 95% CI, 1.34-3.11; P < 0.001). Our meta-analysis demonstrates that patients with COVID-19 infection presenting with elevated D-dimer levels have an increased risk of severe disease and mortality.

FIGURE 1.

Flow diagram illustrating the systematic search of studies

FIGURE 2.

d-Dimer levels. The Forest plot for pooled weighted mean difference in d-dimer levels in dead versus survived COVID-19 patients. COVID-19 indicates coronavirus disease 2019.

FIGURE 3.

All-cause mortality. The Forest plot shows the outcomes of the individual trials as well as the aggregate.

FIGURE 4.

Disease severity. A, The Forest plot for pooled weighted mean difference in d-dimer levels in severe versus nonsevere COVID-19 patients, followed by random-effects meta-regression analysis plots depicting the relationship between weighted mean differences in d-dimer levels (on y-axis) and (B) CAD and (C) CRP. Each included study is represented by a circle, the size of which is proportional to its respective weight in the analysis. The line indicates the predicted effects (regression line). There was significant association between CAD (β = 0.8, P = 0.02), and CRP levels (β = 0.02, P = 0.03) and mean differences in d-dimer levels. COVID-19 indicates coronavirus disease 2019; CAD, coronary artery disease; CRP, C-reactive protein.

FIGURE 5.

The Forest plot demonstrating the risk ratio of positive d-dimer with severity.