Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With Coronavirus Disease 2019 Pneumonia

Chest. 2021 Jan 16;S0012-3692(21)00047-7. doi: 10.1016/j.chest.2021.01.017. Online ahead of print.


Background: Because of the high risk of thrombotic complications (TCs) during severe acute respiratory syndrome coronavirus 2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.

Research question: What is the incidence of TC in critically ill patients with coronavirus disease 2019 (COVID-19) and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?

Study design and methods: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.

Results: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99]) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).

Interpretation: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill COVID-19 patients without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.

Trial registry:; No.: NCT04405869; URL:

Keywords: COVID-19; anticoagulation; bleeding; thrombosis.

Associated data