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

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

2021-01-26

Al-Samkari, Hanny, Shruti Gupta, Rebecca Karp Leaf, Wei Wang, Rachel P. Rosovsky, Samantha K. Brenner, Salim S. Hayek, Hanna Berlin, Rajat Kapoor, Shahzad Shaefi, Michal L. Melamed, Anne Sutherland, Jared Radbel, Adam Green, Brian T. Garibaldi, Anand Srivastava, Amanda Leonberg-Yoo, Alexandre M. Shehata, Jennifer E. Flythe, Arash Rashidi, Nitender Goyal, Lili Chan, Kusum S. Mathews, S. Susan Hedayati, Rajany Dy, Stephanie M. Toth-Manikowski, Jingjing Zhang, Mary Mallappallil, Roberta E. Redfern, Amar D. Bansal, Samuel A. P. Short, Mark G. Vangel, Andrew J. Admon, Matthew W. Semler, Kenneth A. Bauer, Miguel A. Hernán, and David E. Leaf. 2021. "Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19." Annals of internal medicine.

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.

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