Empiric Therapeutic Anticoagulation and Mortality in Critically Ill Patients With Respiratory Failure From SARS‐CoV‐2: A Retrospective Cohort Study

Abstract

The pathophysiology of respiratory failure associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains under investigation. One hypothesis is that progressive endothelial damage from the virus leads to microvascular thrombosis. It is uncertain if empiric therapeutic anticoagulation provides benefit over standard deep vein thrombosis (DVT) prophylaxis in critically ill patients with SARS-CoV-2. A retrospective cohort study was performed to evaluate adult patients admitted to the intensive care unit at 3 hospitals with polymerase chain reaction-confirmed SARS-CoV-2-associated respiratory failure requiring invasive mechanical ventilation. A Kaplan-Meier survival analysis was used to compare patients who were initiated on therapeutic anticoagulation prior to the time of intubation and those receiving standard DVT prophylaxis doses. The primary outcome was the difference in the 28-day mortality of patients between the 2 groups. Twenty-eight-day mortality did not differ between groups, occurring in 26.1% of patients who received therapeutic anticoagulation and 29.5% of those who received a prophylactic dose only (hazard ratio, 0.52; P = .055). There was no difference in 28-day mortality between groups in patients who were admitted with a serum D-dimer ≥ 2 μg/mL (hazard ratio, 0.67; P = .41). Empiric therapeutic anticoagulation in patients who require invasive mechanical ventilation for confirmed SARS-CoV-2 infection does not improve 28-day mortality compared with standard DVT prophylaxis, even among those with elevated D-dimer levels.

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

“…Results from previous studies investigating the role of anticoagulation among patients with covid-19 have varied 13143031323334353637. Variations in reported associations probably derive from different definitions of anticoagulation, for both drug type and dose.…”

Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis

“…39-41 Retrospective studies of therapeutic-compared to prophylactic-dose anticoagulation have reported mixed effects on mortality, while only two small studies have examined outcomes with intermediate-compared to prophylactic-dose anticoagulation, largely focusing on venous thromboembolism rates, again with conflicting results. 7,15,16,18-22,42,43 More recently, the ACTIV randomized clinical trial showed futility of therapeutic-compared to prophylactic-dose anticoagulation in critically ill COVID-19 patients, leading to a pause in further recruitment of critically ill patients for that trial. Our analysis is the first large-scale study to specifically examine intermediate- and prophylactic-dose anticoagulation in COVID-19.…”

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

“…A retrospective secondary analysis of 141 intubated COVID-19 patients from three hospitals in the United States found no difference in 28day mortality from time of intubation when empirically treated with therapeutic dose anticoagulation compared with standard DVT prophylactic doses, even among those with D-dimer levels > 2 μg/mL. 38 As only intubated patients were included, it is unclear whether therapeutic anticoagulation in a general medical ward may reduce progression to intubation or incidence of VTE. A retrospective study from the United States analyzed 3,625 COVID-19 patients with moderate or severe illness finding that therapeutic anticoagulation including apixaban has similar efficacy to enoxaparin in decreasing mortality in hospitalized COVID-19 patients.…”