Samuel A P Short1, Shruti Gupta2, Samantha K Brenner3,4, Salim S Hayek5, Anand Srivastava6, Shahzad Shaefi7, Harkarandeep Singh2, Benjamin Wu8, Aranya Bagchi9, Hanny Al-Samkari10, Rajany Dy11, Katherine Wilkinson12, Neil A Zakai12,13, David E Leaf2. 1. Larner College of Medicine, University of Vermont, Burlington, VT. 2. Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA. 3. Department of Internal Medicine, Hackensack Meridian School of Medicine at Seton Hall, Nutley, NJ. 4. Department of Internal Medicine, Heart & Vascular Hospital, Hackensack Meridian Health Hackensack University Medical Center, Hackensack, NJ. 5. Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor, MI. 6. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL. 7. Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA. 8. Division of Pulmonary, Critical Care & Sleep Medicine, NYU Langone Medical Center, New York, NY. 9. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. 10. Division of Hematology, Massachusetts General Hospital, Boston, MA. 11. Department of Medicine, University Medical Center of Southern Nevada Hospital, University of Nevada, Las Vegas, NV. 12. Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT. 13. Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT.
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.
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.
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