Ann Intern Med
. 2021 Jan 26.
doi: 10.7326/M20-6739. Online ahead of print.
Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19
Hanny Al-Samkari 1 , Shruti Gupta 2 , Rebecca Karp Leaf 1 , Wei Wang 3 , Rachel P Rosovsky 1 , Samantha K Brenner 4 , Salim S Hayek 5 , Hanna Berlin 5 , Rajat Kapoor 6 , Shahzad Shaefi 7 , Michal L Melamed 8 , Anne Sutherland 9 , Jared Radbel 10 , Adam Green 11 , Brian T Garibaldi 12 , Anand Srivastava 13 , Amanda Leonberg-Yoo 14 , Alexandre M Shehata 15 , Jennifer E Flythe 16 , Arash Rashidi 17 , Nitender Goyal 18 , Lili Chan 19 , Kusum S Mathews 19 , S Susan Hedayati 20 , Rajany Dy 21 , Stephanie M Toth-Manikowski 22 , Jingjing Zhang 23 , Mary Mallappallil 24 , Roberta E Redfern 25 , Amar D Bansal 26 , Samuel A P Short 27 , Mark G Vangel 28 , Andrew J Admon 29 , Matthew W Semler 30 , Kenneth A Bauer 31 , Miguel A Hern?n 32 , David E Leaf 2
Affiliations
- PMID: 33493012
- DOI: 10.7326/M20-6739
Abstract
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.