Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy

Corrado Lodigiani, Giacomo Iapichino, Luca Carenzo, Maurizio Cecconi, Paola Ferrazzi, Tim Sebastian, Nils Kucher, Jan-Dirk Studt, Clara Sacco, Alexia Bertuzzi, Maria Teresa Sandri, Stefano Barco, Humanitas COVID-19 Task Force, Corrado Lodigiani, Giacomo Iapichino, Luca Carenzo, Maurizio Cecconi, Paola Ferrazzi, Tim Sebastian, Nils Kucher, Jan-Dirk Studt, Clara Sacco, Alexia Bertuzzi, Maria Teresa Sandri, Stefano Barco, Humanitas COVID-19 Task Force

Abstract

Background: Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.

Methods: We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC).

Results: We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients.

Conclusions: The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.

Keywords: COVID-19; Cardiovascular complications; Disseminated intravascular coagulation; Mortality; SARS-CoV2; Venous thromboembolism.

Conflict of interest statement

Declaration of competing interest Corrado Lodigiani received congress and travel payments from Bayer HealthCare, Daiichi-Sankyo and Boehringer Ingelheim, NovoNordisk, Takeda, and honoraria from Daiichi-Sankyo, Takeda, NovoNordisk, Boehringer Ingelheim, Bayer HealthCare, Aspen, Italfarmaco. Stefano Barco has received congress and travel payments from Daiichi-Sankyo and Bayer HealthCare, and honoraria from Bayer HealthCare and LeoPharma. The other authors do not disclose any potential conflict of interest. The present study was not funded.

Copyright © 2020. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Probability of in-hospital death across age. We performed logistic regression to ascertain the effects of age on the likelihood that patients died during hospitalization (Odds Ratio 1.10; 95%CI 1.07–1.13). The figure depicts the probability of in-hospital death across age. The analysis was restricted to closed cases (dead or discharged at the time of analysis).

References

    1. Worldometer COVID-19 Data. Available at.
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062.
    1. Ruan Q., Yang K., Wang W., Jiang L., Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020:1–3.
    1. Han H., Yang L., Liu R., Liu F., Wu K.L., Li J., et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin. Chem. Lab. Med. 2020 doi: 10.1515/cclm-2020-0188.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
    1. Tang N., Bai H., Chen X., Gong J., Li D., Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J. Thromb. Haemost. 2020 doi: 10.1111/jth.14817.
    1. Varga S., Flammer A., Steiger P., Haberecker M., Andermatt R., Zinkernagel A., et al. 2020. Endothelial Cell Infection and Endotheliitis in COVID-19.
    1. Clerkin K.J., Fried J.A., Raikhelkar J., Sayer G., Griffin J.M., Masoumi A., et al. Coronavirus disease 2019 (COVID-19) and cardiovascular disease. Circulation. 2020 doi: 10.1161/CIRCULATIONAHA.120.046941.
    1. Klok F.A., Kruip M.J.H.A., van der Meer N.J.M., Arbous M.S., Gommers D.A.M.P.J., Kant K.M., et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020 doi: 10.1016/j.thromres.2020.04.013.
    1. 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 doi: 10.1111/jth.14830.
    1. Toh CH, Hoots WK, ISTH SSCoDICot. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J. Thromb. Haemost. 2007;5(3):604–6.
    1. Samama M.M., Cohen A.T., Darmon J.Y., Desjardins L., Eldor A., Janbon C., et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N. Engl. J. Med. 1999;341(11):793–800.
    1. Kaplan D., Casper T.C., Elliott C.G., Men S., Pendleton R.C., Kraiss L.W., et al. VTE incidence and risk factors in patients with severe sepsis and septic shock. Chest. 2015;148(5):1224–1230.
    1. Zhang C., Zhang Z., Mi J., Wang X., Zou Y., Chen X., et al. The cumulative venous thromboembolism incidence and risk factors in intensive care patients receiving the guideline-recommended thromboprophylaxis. Medicine (Baltimore) 2019;98(23)
    1. Helms J., Tacquard C., Severac F., Leonard-Lorant I., Ohana M., Delabranche X., et al. High risk of thrombosis in patients in severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020 doi: 10.1007/s00134-020-06062-x.
    1. Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J. Thromb. Haemost.
    1. Schunemann H.J., Cushman M., Burnett A.E., Kahn S.R., Beyer-Westendorf J., Spencer F.A., et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2(22):3198–3225.
    1. Lang J., Yang N., Deng J., Liu K., Yang P., Zhang G., et al. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS One. 2011;6(8)
    1. Mycroft-West C et al. The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. bioRxiv preprint doi: 10.1101/2020.02.29.97109.
    1. Thachil J. The versatile heparin in COVID-19. J. Thromb. Haemost. 10.1111/jth.14821.

Source: PubMed

3
Abonneren