Impact of high dose prophylactic anticoagulation in critically ill patients with COVID-19 pneumonia

Tacquard, Charles; Mansour, Alexandre; Godon, Alexandre; Godet, Julien; Poissy, Julien; Garrigue, Delphine; Kipnis, Eric; Hamada, Sophie Rym; Mertes, Paul Michel; Steib, Annick; Ulliel-Roche, Mathilde; Bouhemad, Bélaïd; Nguyen, Maxime; Reizine, Florian; Gouin-Thibault, Isabelle; Besse, Marie Charlotte; Collercandy, Nived; Mankikian, Stefan; Levy, Jerrold H.; Gruel, Yves; Albaladejo, Pierre; Susen, Sophie; Godier, Anne

Background Due to the high risk of thrombotic complications (TC) during SARS-CoV-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 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 intensive care units (ICU) for COVID-19 were included in our 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 Out of 538 patients included, 104 patients developed a total of 122 TC with an incidence of 22.7 % (19.2-26.3). Pulmonary embolism accounted for 52 % of the recorded TC. High dose prophylactic anticoagulation was associated with a significant reduced risk of TC (HR 0.81 [0.66-0.99]) without increasing the risk of bleeding (HR 1.11 [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.