Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19

J Am Coll Cardiol. 2020 Oct 20;76(16):1815-1826. doi: 10.1016/j.jacc.2020.08.041. Epub 2020 Aug 26.

Abstract

Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.

Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.

Methods: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies.

Results: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC.

Conclusions: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.

Keywords: COVID-19; anticoagulation; intubation; mortality.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Anticoagulants* / classification
  • Anticoagulants* / therapeutic use
  • Autopsy / statistics & numerical data*
  • Betacoronavirus / isolation & purification
  • Blood Coagulation
  • COVID-19
  • Coronavirus Infections* / blood
  • Coronavirus Infections* / complications
  • Coronavirus Infections* / mortality
  • Coronavirus Infections* / therapy
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / prevention & control
  • Hospital Mortality
  • Hospitalization / statistics & numerical data*
  • Humans
  • Male
  • New York City / epidemiology
  • Outcome and Process Assessment, Health Care
  • Pandemics*
  • Pneumonia, Viral* / blood
  • Pneumonia, Viral* / complications
  • Pneumonia, Viral* / mortality
  • Pneumonia, Viral* / therapy
  • Post-Exposure Prophylaxis* / methods
  • Post-Exposure Prophylaxis* / statistics & numerical data
  • Risk Adjustment / methods
  • SARS-CoV-2
  • Thromboembolism* / drug therapy
  • Thromboembolism* / mortality
  • Thromboembolism* / prevention & control
  • Thromboembolism* / virology

Substances

  • Anticoagulants