Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

Link: https://doi.org/10.7326/M20-6739
Authors: Al-Samkari, Hanny; Gupta, Shruti; Leaf, Rebecca Karp; Wang, Wei; Rosovsky, Rachel P; Brenner, Samantha K; Hayek, Salim S; Berlin, Hanna; Kapoor, Rajat; Shaefi, Shahzad; Melamed, Michal L; Sutherland, Anne; Radbel, Jared; Green, Adam; Garibaldi, Brian T; Srivastava, Anand; Leonberg-Yoo, Amanda; Shehata, Alexandre M; Flythe, Jennifer E; Rashidi, Arash; Goyal, Nitender; Chan, Lili; Mathews, Kusum S; Hedayati, S Susan; Dy, Rajany; Toth-Manikowski, Stephanie M; Zhang, Jingjing; Mallappallil, Mary; Redfern, Roberta E; Bansal, Amar D; Short, Samuel A P; Vangel, Mark G; Admon, Andrew J; Semler, Matthew W; Bauer, Kenneth A; Hernán, Miguel A; Leaf, David E; ,

Abstract: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. 67 hospitals in the United States. Adults with COVID-19 admitted to a participating ICU. Time to death, censored at hospital discharge, or date of last follow-up. Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Observational design. Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. None.