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Factors Associated With Risk of Postdischarge Thrombosis in Patients With COVID-19

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Which patients with COVID-19 may benefit from extended thromboprophylaxis following hospital discharge?

Findings  In this cohort study of 2832 patients hospitalized with COVID-19, postdischarge venous thromboembolic events occurred more often in those with a history of venous thromboembolism, peak dimerized plasmin fragment D (D-dimer) level greater than 3 μg/mL, and predischarge C-reactive protein level greater than 10 mg/dL. Patients who received postdischarge anticoagulation therapy had fewer events.

Meaning  These findings suggest that postdischarge anticoagulation therapy may be considered for high-risk patients with COVID-19.

Abstract

Importance  COVID-19 is associated with a high incidence of thrombotic events; however, the need for extended thromboprophylaxis after hospitalization remains unclear.

Objective  To quantify the rate of postdischarge arterial and venous thromboembolism in patients with COVID-19, identify the factors associated with the risk of postdischarge venous thromboembolism, and evaluate the association of postdischarge anticoagulation use with venous thromboembolism incidence.

Design, Setting, and Participants  This is a cohort study of adult patients hospitalized with COVID-19 confirmed by a positive SARS-CoV-2 test. Eligible patients were enrolled at 5 hospitals of the Henry Ford Health System from March 1 to November 30, 2020. Data analysis was performed from April to June 2021.

Exposures  Anticoagulant therapy after discharge.

Main Outcomes and Measures  New onset of symptomatic arterial and venous thromboembolic events within 90 days after discharge from the index admission for COVID-19 infection were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes.

Results  In this cohort study of 2832 adult patients hospitalized with COVID-19, the mean (SD) age was 63.4 (16.7) years (IQR, 53-75 years), and 1347 patients (47.6%) were men. Thirty-six patients (1.3%) had postdischarge venous thromboembolic events (16 pulmonary embolism, 18 deep vein thrombosis, and 2 portal vein thrombosis). Fifteen (0.5%) postdischarge arterial thromboembolic events were observed (1 transient ischemic attack and 14 acute coronary syndrome). The risk of venous thromboembolism decreased with time (Mann-Kendall trend test, P < .001), with a median (IQR) time to event of 16 (7-43) days. There was no change in the risk of arterial thromboembolism with time (Mann-Kendall trend test, P = .37), with a median (IQR) time to event of 37 (10-63) days. Patients with a history of venous thromboembolism (odds ratio [OR], 3.24; 95% CI, 1.34-7.86), peak dimerized plasmin fragment D (D-dimer) level greater than 3 μg/mL (OR, 3.76; 95% CI, 1.86-7.57), and predischarge C-reactive protein level greater than 10 mg/dL (OR, 3.02; 95% CI, 1.45-6.29) were more likely to experience venous thromboembolism after discharge. Prescriptions for therapeutic anticoagulation at discharge were associated with reduced incidence of venous thromboembolism (OR, 0.18; 95% CI, 0.04-0.75; P = .02).

Conclusions and Relevance  Although extended thromboprophylaxis in unselected patients with COVID-19 is not supported, these findings suggest that postdischarge anticoagulation may be considered for high-risk patients who have a history of venous thromboembolism, peak D-dimer level greater than 3 μg/mL, and predischarge C-reactive protein level greater than 10 mg/dL, if their bleeding risk is low.

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Article Information

Accepted for Publication: September 26, 2021.

Published: November 22, 2021. doi:10.1001/jamanetworkopen.2021.35397

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Li P et al. JAMA Network Open.

Corresponding Author: Pin Li, PhD, Department of Public Health Sciences, Henry Ford Health System, One Ford Place, Detroit, MI 48202 (pli3@hfhs.org).

Author Contributions: Dr Li had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Li and Zhao made equal contributions to this study.

Concept and design: Li, Zhao, Kaatz, Poisson.

Acquisition, analysis, or interpretation of data: Li, Zhao, Latack, Schultz, Poisson.

Drafting of the manuscript: Li, Zhao, Latack, Schultz.

Critical revision of the manuscript for important intellectual content: Li, Zhao, Kaatz, Schultz, Poisson.

Statistical analysis: Li, Schultz.

Administrative, technical, or material support: Li.

Supervision: Kaatz, Poisson.

Conflict of Interest Disclosures: Dr Kaatz reported receiving personal fees from Norvartis, Janssen, Bristol Myers Squibb, Pfizer, CSL Behring, Portola/Alexion, and Gilead; and grants from Osmosis Research, National Institutes of Health, Bristol Myers Squibb, and Janssen outside the submitted work. No other disclosures were reported.

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