Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis

Sakka, Mehdi; Connors, Jean M; Hékimian, Guillaume; Martin-Toutain, Isabelle; Crichi, Benjamin; Colmegna, Ines; Bonnefont-Rousselot, Dominique; Farge, Dominique; Frere, Corinne

Abstract Background: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts. Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19. Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI). Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59 µg/L (95% CI 2.79–4.40 µg/L), and the Z-score for overall effect was 8.74 (p < 0.00001), with a high heterogeneity across studies (I²=95%). Conclusions: Despite high heterogeneity across included studies, the present pooled analysis indicates that D-Dimer levels are significantly associated with the risk of mortality in COVID-19 patients. Early integration of D-Dimer testing, which is a rapid, inexpensive, and easily accessible biological test, can be useful to better risk stratification and management of COVID-19 patients.