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

Short, Samuel A P; Gupta, Shruti; Brenner, Samantha K; Hayek, Salim S; Srivastava, Anand; Shaefi, Shahzad; Singh, Harkarandeep; Wu, Benjamin; Bagchi, Aranya; Al-Samkari, Hanny; Dy, Rajany; Wilkinson, Katherine; Zakai, Neil A; Leaf, David E

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.