Rim Halaby1, Adam Cuker1,2, Jennifer Yui3, Andrew Matthews1, Ella Ishaaya4, Elizabeth Traxler1, Christopher Domenico5, Tara Cooper5, Ann Tierney6, Pardis Niami5, Nathalie van der Rijst1, Srinath Adusumalli1, Jacob Gutsche7, Jay Giri1, Steven Pugliese1, Todd E H Hecht1, Allyson M Pishko1. 1. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 2. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. 4. Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA. 5. Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. 6. Department of Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 7. Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
BACKGROUND: Studies report hypercoagulability in coronavirus disease 2019 (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 with 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: Four hundred and forty-three 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% confidence interval [CI]: 0.86-1.86). In COVID-19 patients, an inverse-probability treatment weighted 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 with 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 with 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.
BACKGROUND: Studies report hypercoagulability in coronavirus disease 2019 (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 illpatients with COVID-19 compared with 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: Four hundred and forty-three 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% confidence interval [CI]: 0.86-1.86). In COVID-19patients, an inverse-probability treatment weighted 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 with 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 with standard thromboprophylaxis was 2.59 (95% CI: 1.20-5.57). CONCLUSIONS:Critically illpatients with COVID-19 had a similar bleeding risk as ORVI patients. When accounting for changes in anticoagulation that occurred in COVID-19patients, therapeutic-intensity anticoagulation was associated with a greater risk of major bleeding compared with standard thromboprophylaxis.
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