Prophylactic versus therapeutic dose anticoagulation effects on survival among critically ill patients with COVID-19

PLoS One. 2022 Jan 19;17(1):e0262811. doi: 10.1371/journal.pone.0262811. eCollection 2022.

Abstract

Introduction: Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics.

Materials and methods: We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model.

Results: For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease.

Conclusions: Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.

MeSH terms

  • Acute Kidney Injury / complications
  • Acute Kidney Injury / diagnosis
  • Age Factors
  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • COVID-19 / mortality
  • COVID-19 / pathology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Cardiovascular Diseases / complications
  • Critical Illness
  • Female
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • SARS-CoV-2 / isolation & purification
  • Sex Factors
  • Thrombosis / complications
  • Thrombosis / drug therapy*

Substances

  • Anticoagulants

Grants and funding

The author(s) received no specific funding for this work.