Bleeding Risk by Intensity of Anticoagulation in Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Background Studies report hypercoagulability in COVID-19, leading many institutions to escalate anticoagulation intensity for thrombosis prophylaxis OBJECTIVE: To determine the bleeding risk with various intensities of anticoagulation in critically-ill patients with COVID-19 compared to other respiratory viral illnesses (ORVI). Patients/methods This retrospective cohort study compared the incidence of major bleeding in patients admitted to an intensive care unit (ICU) within a single health system with COVID-19 versus ORVI. In the COVID-19 cohort, we assessed the effect of anticoagulation intensity received on ICU admission on bleeding risk. We performed a secondary analysis with anticoagulation intensity as a time-varying covariate to reflect dose changes after ICU admission. Results 443 and 387 patients were included in the COVID-19 and ORVI cohorts, respectively. The hazard ratio of major bleeding for the COVID-19 cohort relative to the ORVI cohort was 1.26 (95% CI 0.86-1.86). In COVID-19 patients, an inverse-probability treatment weighted (IPTW) model found therapeutic-intensity anticoagulation on ICU admission had an adjusted hazard ratio of bleeding of 1.55 (95% CI 0.88-2.73) compared to standard prophylactic-intensity anticoagulation. However, when anticoagulation was assessed as a time-varying covariate and adjusted for other risk factors for bleeding, the adjusted hazard ratio for bleeding on therapeutic-intensity anticoagulation compared to standard thromboprophylaxis was 2.59 (95% CI 1.20-5.57). Conclusions Critically ill patients with COVID-19 had a similar bleeding risk as ORVI patients. When accounting for changes in anticoagulation that occurred in COVID-19 patients, therapeutic-intensity anticoagulation was associated with a greater risk of major bleeding compared with standard thromboprophylaxis.