Therapeutic anticoagulation may not provide a survival benefit for critically ill patients with COVID-19, according to research published in the Annals of Internal Medicine.

It is becoming more recognized that hypercoagulability in patients with COVID-19 is a leading cause of mortality from the disease. Data on the incidence of venous thromboembolism (VTE) are mostly based on single-center observational reports. Some experts recommend therapeutic anticoagulation for critically ill patients with COVID-19; however, no randomized trials have been conducted yet.

In this observational study, the authors evaluated the incidence of VTE and whether early anticoagulation affected survival. They used data from 3239 critically ill adults with COVID-19 in intensive care units (ICUs) across 67 hospitals in the United States.

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During the study period, 39.3% of patients died, 43.4% were discharged from the hospital within 28 days, and 17.4% were still hospitalized at 28 days. Routine screening for VTE was conducted in 3 hospitals. Out of the patient populations, 204 (6.3%) had VTE and 2.8% had a major bleeding event during the first 14 days of ICU admission. Patients with confirmed VTE had a 28-day mortality of 38.2%, and patients with stroke had a 28-day mortality of 55%.

In the study cohort, men were at higher risk for VTE, as were patients with higher D-dimer levels at ICU admission.

All 67 hospitals reported administering standard prophylactic doses of anticoagulation to all critically ill patients with COVID-19. Of these patients, 43.6% received therapeutic anticoagulation within 14 days of ICU admission, with a median time to initiation of 3 days.

In the target trial emulation of therapeutic anticoagulation, 2809 patients were included. Of these patients, 11.9% received anticoagulation therapy within 2 days of ICU admission. At a median follow-up of 27 days, 46.6% of the patients treated with early anticoagulation therapy died vs 36.6% of patients not treated early.

Overall, the authors found no survival benefit from early anticoagulation therapy for the group as a whole nor for any subgroup. The authors suggested that therapeutic anticoagulation may reduce the risk of VTE but increase the risk for major bleeding. Patients with major bleeding were found to have higher mortality rates.

“Our findings do not support early empirical use of therapeutic anticoagulation in critically ill patients with COVID-19,” the authors concluded.


Al-Samkari H, Gupta S, Leaf RK, et al. Thrombosis, bleeding, and the observational effect of early therapeutic anticoagulation on survival in critically ill patients With COVID-19. Ann Intern Med. Published online January 26, 2021. doi:10.7326/M20-6739