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

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.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: 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. DESIGN: 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. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: 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]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.