Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System | Coagulation Disorders | JAMA | JAMA Network
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Table 1.  Incidence of Thrombotic Events in Hospitalized Patients With COVID-19
Incidence of Thrombotic Events in Hospitalized Patients With COVID-19
Table 2.  Adjusted Hazard Ratios for Any Thrombosis, Venous Thrombosis, and Arterial Thrombosis in Hospitalized Patients With COVID-19 (N = 3334)
Adjusted Hazard Ratios for Any Thrombosis, Venous Thrombosis, and Arterial Thrombosis in Hospitalized Patients With COVID-19 (N = 3334)
1.
Connors  JM, Levy  JH.  COVID-19 and its implications for thrombosis and anticoagulation.   Blood. 2020;135(23):2033-2040. doi:10.1182/blood.2020006000PubMedGoogle ScholarCrossref
2.
Swartz  J, Koziatek  C, Theobald  J, Smith  S, Iturrate  E.  Creation of a simple natural language processing tool to support an imaging utilization quality dashboard.   Int J Med Inform. 2017;101:93-99. doi:10.1016/j.ijmedinf.2017.02.011PubMedGoogle ScholarCrossref
3.
Cui  S, Chen  S, Li  X, Liu  S, Wang  F.  Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.   J Thromb Haemost. 2020;18(6):1421-1424. doi:10.1111/jth.14830 PubMedGoogle ScholarCrossref
4.
Klok  FA, Kruip  MJHA, van der Meer  NJM,  et al.  Incidence of thrombotic complications in critically ill ICU patients with COVID-19.   Thromb Res. 2020;191:145-147. doi:10.1016/j.thromres.2020.04.013PubMedGoogle ScholarCrossref
5.
Grimnes  G, Isaksen  T, Tichelaar  YIGV, Brækkan  SK, Hansen  JB.  Acute infection as a trigger for incident venous thromboembolism: results from a population-based case-crossover study.   Res Pract Thromb Haemost. 2017;2(1):85-92. doi:10.1002/rth2.12065PubMedGoogle ScholarCrossref
6.
Bunce  PE, High  SM, Nadjafi  M, Stanley  K, Liles  WC, Christian  MD.  Pandemic H1N1 influenza infection and vascular thrombosis.   Clin Infect Dis. 2011;52(2):e14-e17. doi:10.1093/cid/ciq125PubMedGoogle ScholarCrossref
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    Research Letter
    July 20, 2020

    Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System

    Author Affiliations
    • 1Department of Population Health, New York University Langone Health, New York, New York
    • 2Department of Medicine, New York University Langone Health, New York, New York
    JAMA. 2020;324(8):799-801. doi:10.1001/jama.2020.13372

    Patients with coronavirus disease 2019 (COVID-19) are at increased risk of thrombosis.1 However, studies have been limited in size, did not report all thrombotic events, and focused on patients with severe disease hospitalized in intensive care units (ICUs). We assessed the incidence of, and risk factors for, venous and arterial thrombotic events in all hospitalized patients with COVID-19 at a large health system consisting of 4 hospitals in New York City.

    Methods

    This study included consecutive patients aged at least 18 years, admitted to a hospital affiliated with NYU Langone Health between March 1 and April 17, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcriptase–polymerase chain reaction of patient sputum or nasopharyngeal or oropharyngeal swabs. This study was approved by the NYU Grossman School of Medicine Institutional Review Board, which waived the need for informed consent.

    Screening for thrombotic events is not standard; diagnoses were made during routine clinical care. Thrombotic events included both venous (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and arterial (myocardial infarction [MI], ischemic stroke, and other systemic thromboembolism). Low-dose (prophylaxis) anticoagulation was used in most patients. As described previously,2 an open-source natural-language processing tool called simpleNLP, with sensitivity and specificity greater than 95%, searched clinical notes and radiology reports for thrombotic events. Additional chart reviews were performed on echocardiograms, presumptive diagnoses, and diagnostic codes for thrombotic end points. All findings were confirmed by manual chart review. Covariate information was obtained from chart review, and mortality was defined as in-hospital death or discharge to hospice as of June 1, 2020.

    We investigated risk factors for thrombotic events and conducted competing risk survival analyses. For the end point of mortality, competing risk was discharge; for the end point of thrombosis, competing risks were death or discharge. Variables were included in the models because of their known association with the outcome of interest and statistical differences on multivariable testing, including age, sex, race/ethnicity, body mass index, smoking, comorbidities, and D-dimer levels.

    Statistical analyses were conducted using Rstudio (R version 3.5.1). A 2-tailed P< .05 was considered statistically significant.

    Results

    Among 3334 consecutive hospitalized COVID-19 patients, the median age was 64 (interquartile range, 51-75) years; 39.6% were female. Any thrombotic event (patients could have more than 1) occurred in 533 (16.0%) patients; 207 (6.2%) were venous (3.2% PE and 3.9% DVT) and 365 (11.1%) were arterial (1.6% ischemic stroke, 8.9% MI, and 1.0% systemic thromboembolism; Table 1). Following multivariable adjustment, age, sex, Hispanic ethnicity, coronary artery disease, prior MI, and higher D-dimer levels at hospital presentation were associated with a thrombotic event (Table 2).

    All-cause mortality was 24.5% and was higher in those with thrombotic events (43.2% vs 21.0%; P < .001) (Table 1). After multivariable adjustment, a thrombotic event was independently associated with mortality (adjusted hazard ratio, 1.82; 95% CI, 1.54-2.15; P < .001). Both venous (adjusted hazard ratio, 1.37; 95% CI, 1.02-1.86; P = .04) and arterial (adjusted hazard ratio, 1.99; 95% CI, 1.65-2.40; P < .001) thrombosis were associated with mortality (P = .25 for interaction).

    Among 829 ICU patients, 29.4% had a thrombotic event (13.6% venous and 18.6% arterial). Among 2505 non-ICU patients, 11.5% had a thrombotic event (3.6% venous and 8.4% arterial).

    Discussion

    In patients with COVID-19 hospitalized in a large New York City health system, a thrombotic event occurred in 16.0%. D-dimer level at presentation was independently associated with thrombotic events, consistent with an early coagulopathy.

    Prior studies varied regarding the precise incidence of thrombosis; however, all suggested a heightened risk in patients with COVID-19.3,4 This analysis found variation by clinical setting and type of thrombosis event. While thrombosis is observed in other acute infections5 (eg, 5.9% prevalence during the 2009 influenza pandemic),6 the thrombotic risk appears higher in COVID-19. Thrombosis in patients with COVID-19 may be due to a cytokine storm, hypoxic injury, endothelial dysfunction, hypercoagulability, and/or increased platelet activity.

    This study has several limitations. A diagnosis of thrombosis may be underestimated because imaging studies were limited due to concerns of transmitting infection or competing risk of death. Type of MI was not confirmed with cardiac catheterization. Clinical practice changed over the study period, with increased awareness of thrombotic events and use of anticoagulation, which may affect the incidence of thrombosis.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Corresponding Author: Jeffrey S. Berger, MD, MS, Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, 530 First Ave, Skirball 9R, New York, NY 10016 (jeffrey.berger@nyulangone.org).

    Accepted for Publication: July 8, 2020.

    Published Online: July 20, 2020. doi:10.1001/jama.2020.13372

    Correction: This article was corrected on July 29, 2020, to fix the hazard ratios for male sex and current smoker in Table 2.

    Author Contributions: Dr Berger had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Bilaloglu, Iturrate, Hochman, Berger.

    Acquisition, analysis, or interpretation of data: Bilaloglu, Aphinyanaphongs, Jones, Iturrate.

    Drafting of the manuscript: Bilaloglu, Iturrate, Berger.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Bilaloglu, Jones.

    Administrative, technical, or material support: Bilaloglu, Iturrate, Berger.

    Supervision: All authors.

    Conflict of Interest Disclosures: Dr Hochman reported receiving support for drug distribution related to the ISCHEMIA Trial and in-kind donations for participating sites from AstraZeneca Pharmaceuticals and Arbor Pharmaceuticals; in-kind donations for participating sites from Abbott Vascular, Medtronic Inc, St Jude Medical Inc, Volcano Corp, Merck Sharp & Dohme Corp, Omron Healthcare Inc, and Amgen Inc; and grants from the National Heart, Lung, and Blood Institute for serving as chair of the ISCHEMIA study. Dr Berger reported receiving grants from AstraZeneca, personal fees from Janssen, and personal fees from Amgen outside the submitted work. No other disclosures were reported.

    Funding/Support: Funding for this project was supported in part by New York University (NYU) CTSA grant UL1TR001445 from the National Center for Advancing Translational Sciences. Dr Berger is funded in part by the National Heart, Lung, and Blood Institute (grants R01HL139909 and R35HL144993).

    Role of the Funder/Sponsor: The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We acknowledge Meng Cao, BSE, Siddhant Dogra, BS, Ruina Zhang, AB, and Emma Simon, BS, who reviewed the clinical charts, and Ji Chen, MS, who queried data, all from the NYU Grossman School of Medicine. There was no financial compensation for these contributions.

    References
    1.
    Connors  JM, Levy  JH.  COVID-19 and its implications for thrombosis and anticoagulation.   Blood. 2020;135(23):2033-2040. doi:10.1182/blood.2020006000PubMedGoogle ScholarCrossref
    2.
    Swartz  J, Koziatek  C, Theobald  J, Smith  S, Iturrate  E.  Creation of a simple natural language processing tool to support an imaging utilization quality dashboard.   Int J Med Inform. 2017;101:93-99. doi:10.1016/j.ijmedinf.2017.02.011PubMedGoogle ScholarCrossref
    3.
    Cui  S, Chen  S, Li  X, Liu  S, Wang  F.  Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.   J Thromb Haemost. 2020;18(6):1421-1424. doi:10.1111/jth.14830 PubMedGoogle ScholarCrossref
    4.
    Klok  FA, Kruip  MJHA, van der Meer  NJM,  et al.  Incidence of thrombotic complications in critically ill ICU patients with COVID-19.   Thromb Res. 2020;191:145-147. doi:10.1016/j.thromres.2020.04.013PubMedGoogle ScholarCrossref
    5.
    Grimnes  G, Isaksen  T, Tichelaar  YIGV, Brækkan  SK, Hansen  JB.  Acute infection as a trigger for incident venous thromboembolism: results from a population-based case-crossover study.   Res Pract Thromb Haemost. 2017;2(1):85-92. doi:10.1002/rth2.12065PubMedGoogle ScholarCrossref
    6.
    Bunce  PE, High  SM, Nadjafi  M, Stanley  K, Liles  WC, Christian  MD.  Pandemic H1N1 influenza infection and vascular thrombosis.   Clin Infect Dis. 2011;52(2):e14-e17. doi:10.1093/cid/ciq125PubMedGoogle ScholarCrossref
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