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Thrombosis, Bleeding, and the Effect of Anticoagulation on Survival in Critically Ill Patients with COVID-19 in the United States

1Massachusetts General Hospital, Division of Hematology, Boston, United States, 2Harvard Medical School, Boston, United States, 3Brigham and Women's Hospital, Division of Renal Medicine, Boston, United States, 4Brigham and Women's Hospital, Divisions of Medicine and Neurology, Boston, United States, 5Beth Israel Deaconess Medical Center, Division of Hematology and Oncology, Boston, United States

Abstract Number: LB/CO01.2

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » Thrombophilia

Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19).

Aims: To examine incidence of radiographically-confirmed venous thromboembolism (VTE) and major bleeding in a large nationally-representative U.S. cohort and assess whether therapeutic anticoagulation affects survival.

Methods: In a 67-center cohort study of 3239 critically ill adults with COVID-19, we examined incidence of VTE and major bleeding within 14 days following intensive care unit (ICU) admission. We identified predictors of VTE using multivariable logistic regression. To estimate the effect of therapeutic anticoagulation on 28-day mortality, we emulated a target trial in which critically ill patients with COVID-19 were assigned to receive or not receive therapeutic anticoagulation in the first two days of ICU admission (FIGURE 1). We adjusted for confounding using a Cox model with inverse probability weighting.

Results: Patients’ median age was 61 years (IQR, 53-71) and 2088 (64.5%) were male. 204 patients (6.3%) developed VTE, and 90 (2.8%) had a major bleeding event. Independent predictors of VTE were male sex (odds ratio [OR], 1.70; 95% CI, 1.05-2.77), severe obesity (OR 2.08; 95% CI, 1.17-3.70 for body mass index ≥40.0 versus < 30 kg/m2), and higher D-dimer on ICU day 1 (OR 4.20; 95% CI, 2.17-8.14 for >10,000 versus ≤1000 ng/ml). Among 2809 patients included in the target trial emulation, 384 (11.9%) received therapeutic anticoagulation in the first two days of ICU admission. In the primary analysis, during a median follow-up of 27 days, patients receiving therapeutic anticoagulation had a similar risk of death as those who did not (hazard ratio, 1.12; 95% CI, 0.92 to 1.35), FIGURE 2A. Results were similar in subgroup analyses, FIGURE 2B.

Conclusions: Among 3239 critically ill adults with COVID-19, the 14-day incidence of VTE and major bleeding were 6.3% and 2.8%. Receipt of therapeutic anticoagulation early after ICU admission did not affect survival.


[FIGURE 1. Flow diagram for target trial emulation of therapeutic anticoagulation.]


[ FIGURE 2. Target trial emulation. (A) Survival in patients receiving therapeutic anticoagulation vs. those who did not. (B) Subgroup analyses.]

To cite this abstract in AMA style:

Al-Samkari H, Gupta S, Karp Leaf R, Wang W, Rosovsky R, Bauer K, Leaf D, STOP-COVID Investigators . Thrombosis, Bleeding, and the Effect of Anticoagulation on Survival in Critically Ill Patients with COVID-19 in the United States [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/thrombosis-bleeding-and-the-effect-of-anticoagulation-on-survival-in-critically-ill-patients-with-covid-19-in-the-united-states/. Accessed August 15, 2020.

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