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


Hanny Al-Samkari, Massachusetts General Hospital
Shruti Gupta, Brigham and Women's Hospital
Rebecca Karp Leaf, Massachusetts General Hospital
Wei Wang, Brigham and Women's Hospital
Rachel P. Rosovsky, Massachusetts General Hospital
Samantha K. Brenner, Hackensack University Medical Center
Salim S. Hayek, Michigan Medicine
Hanna Berlin, Michigan Medicine
Rajat Kapoor, Indiana University School of Medicine
Shahzad Shaefi, Beth Israel Deaconess Medical Center
Michal L. Melamed, Albert Einstein College of Medicine of Yeshiva University
Anne Sutherland, Rutgers New Jersey Medical School
Jared Radbel, Rutgers Robert Wood Johnson Medical School
Adam Green, Cooper University Health Care
Brian T. Garibaldi, Johns Hopkins School of Medicine
Anand Srivastava, Northwestern University Feinberg School of Medicine
Amanda Leonberg-Yoo, University of Pennsylvania Perelman School of Medicine
Alexandre M. Shehata, Hackensack Meridian Health-JFK University Medical Center
Jennifer E. Flythe, UNC School of Medicine
Arash Rashidi, University Hospitals Case Medical Center
Nitender Goyal, Tufts Medical Center
Lili Chan, Icahn School of Medicine at Mount Sinai
Kusum S. Mathews, Icahn School of Medicine at Mount Sinai
S. Susan Hedayati, UT Southwestern Medical Center
Rajany Dy, University of Nevada, Las VegasFollow
Stephanie M. Toth-Manikowski, University of Illinois at Chicago
Jingjing Zhang, Thomas Jefferson University Hospital
Mary Mallappallil, Kings County Hospital Center
Roberta E. Redfern, ProMedica Research
Amar D. Bansal

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Annals of internal medicine





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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.None.


Internal Medicine



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