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

Crit Care Med. 2021 May 1;49(5):e500-e511. doi: 10.1097/CCM.0000000000004917.


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.

Trial registration: ClinicalTrials.gov NCT04401293.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Biomarkers / blood
  • COVID-19 / blood*
  • COVID-19 / mortality*
  • COVID-19 / physiopathology
  • Cohort Studies
  • Critical Illness / mortality*
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • SARS-CoV-2*
  • Severity of Illness Index
  • Thrombophilia
  • United States / epidemiology


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D

Associated data

  • ClinicalTrials.gov/NCT04401293