d-dimer and Death in Critically Ill Patients With Coronavirus Disease 2019

Abstract

Objectives: Hypercoagulability may be a key mechanism for acute organ injury and death in patients with severe coronavirus disease 2019, but the relationship between elevated plasma levels of D-dimer, a biomarker of coagulation activation, and mortality has not been rigorously studied. We examined the independent association between D-dimer and death in critically ill patients with coronavirus disease 2019. Design: Multicenter cohort study. Setting: ICUs at 68 hospitals across the United States. Patients: Critically ill adults with coronavirus disease 2019 admitted to ICUs between March 4, 2020, and May 25, 2020, with a measured D-dimer concentration on ICU day 1 or 2. Interventions: None. Measurements and Main Results: The primary exposure was the highest normalized D-dimer level (assessed in four categories: < 2×, 2–3.9×, 4–7.9×, and ≥ 8× the upper limit of normal) on ICU day 1 or 2. The primary endpoint was 28-day mortality. Multivariable logistic regression was used to adjust for confounders. Among 3,418 patients (63.1% male; median age 62 yr [interquartile range, 52–71 yr]), 3,352 (93.6%) had a D-dimer concentration above the upper limit of normal. A total of 1,180 patients (34.5%) died within 28 days. Patients in the highest compared with lowest D-dimer category had a 3.11-fold higher odds of death (95% CI, 2.56–3.77) in univariate analyses, decreasing to a 1.81-fold increased odds of death (95% CI, 1.43–2.28) after multivariable adjustment for demographics, comorbidities, and illness severity. Further adjustment for therapeutic anticoagulation did not meaningfully attenuate this relationship (odds ratio, 1.73; 95% CI, 1.36–2.19). Conclusions: In a large multicenter cohort study of critically ill patients with coronavirus disease 2019, higher D-dimer levels were independently associated with a greater risk of death.