Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization

Abstract

Background Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis.

Methods Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation–perfusion (V/Q) scan to screen for incidental pulmonary embolism.

Results Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported.

Conclusion In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.

Keywords

venous thromboembolism - deep vein thrombosis - pulmonary embolism - COVID-19 - SARS-CoV-2 - anticoagulation - thromboprophylaxis after discharge - postdischarge thromboprophylaxis

^* Contributed equally.

Publication History

Article published online:
23 April 2021

• References

• 1 World Health Organization. WHO coronavirus disease (COVID-19) dashboard. Published 2021. Updated February 5, 2021. Accessed February 5, 2021 at: https://covid19.who.int/
• 2 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
• 3 Fauvel C, Weizman O, Trimaille A. et al; Critical Covid-19 France Investigators. Pulmonary embolism in COVID-19 patients: a French multicentre cohort study. Eur Heart J 2020; 41 (32) 3058-3068
• 4 Klok FA, Kruip MJHA, van der Meer NJM. et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res 2020; 191: 148-150
• 5 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
• 6 Longchamp A, Longchamp J, Manzocchi-Besson S. et al. Venous thromboembolism in critically ill patients with COVID-19: results of a screening study for deep vein thrombosis. Res Pract Thromb Haemost 2020; 4 (05) 842-847
• 7 Middeldorp S, Coppens M, van Haaps TF. et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020; 18 (08) 1995-2002
• 8 Moll M, Zon RL, Sylvester KW. et al. VTE in ICU patients with COVID-19. Chest 2020; 158 (05) 2130-2135
• 9 Stessel B, Vanvuchelen C, Bruckers L. et al. Impact of implementation of an individualised thromboprophylaxis protocol in critically ill ICU patients with COVID-19: a longitudinal controlled before-after study. Thromb Res 2020; 194: 209-215
• 10 Bourguignon A, Beaulieu C, Belkaid W, Desilets A, Blais N. Incidence of thrombotic outcomes for patients hospitalized and discharged after COVID-19 infection. Thromb Res 2020; 196: 491-493
• 11 Kaptein FHJ, Stals MAM, Grootenboers M. et al; Dutch COVID & Thrombosis Coalition. Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave. Thromb Res 2020; 199: 143-148
• 12 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; 18 (05) 1094-1099
• 13 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (04) 844-847
• 14 Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in hospitalized patients with COVID-19 in a New York City Health System. JAMA 2020; 324 (08) 799-801
• 15 Di Castelnuovo A, Costanzo S, Antinori A. et al. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicenter Italian CORIST study. Thromb Haemost 2021; (epub ahead of publication)
• 16 Billett HH, Reyes-Gil M, Szymanski J. et al. Anticoagulation in COVID-19: effect of enoxaparin, heparin, and apixaban on mortality. Thromb Haemost 2020; 120 (12) 1691-1699
• 17 Waite AAC, Hamilton DO, Pizzi R, Ageno W, Welters ID. Hypercoagulopathy in severe COVID-19: implications for acute care. Thromb Haemost 2020; 120 (12) 1654-1667
• 18 Patell R, Midha S, Kimani S. et al. Variability in institutional guidance for COVID-19-associated coagulopathy in the United States. Thromb Haemost 2020; 120 (12) 1725-1732
• 19 Lynn L, Reyes JA, Hawkins K. et al. The effect of anticoagulation on clinical outcomes in novel Coronavirus (COVID-19) pneumonia in a U.S. cohort. Thromb Res 2021; 197: 65-68
• 20 Schulman S, Hu Y, Konstantinides S. Venous thromboembolism in COVID-19. Thromb Haemost 2020; 120 (12) 1642-1653
• 21 Vandenbriele C, Van Aelst L, Balthazar T. et al. Anticoagulant therapy in COVID-19 critically ill: should we go for more?. J Kardiol 2020; 57 (05) 168-170
• 22 Vanassche T, Orlando C, Vandenbosch K. et al. Belgian clinical guidance on anticoagulation management in hospitalised and ambulatory patients with COVID-19. Acta Clin Belg 2020; (e-pub ahead of print)
• 23 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
• 24 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
• 25 Zayed Y, Kheiri B, Barbarawi M. et al. Extended duration of thromboprophylaxis for medically ill patients: a systematic review and meta-analysis of randomised controlled trials. Intern Med J 2020; 50 (02) 192-199
• 26 Patell R, Bogue T, Koshy A. et al. Postdischarge thrombosis and hemorrhage in patients with COVID-19. Blood 2020; 136 (11) 1342-1346
• 27 Roberts LN, Whyte MB, Georgiou L. et al. Postdischarge venous thromboembolism following hospital admission with COVID-19. Blood 2020; 136 (11) 1347-1350
• 28 Bellan M, Soddu D, Balbo PE. et al. Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge. JAMA Netw Open 2021; 4 (01) e2036142
• 29 Chapman DG, Badal T, King GG, Thamrin C. Caution in interpretation of abnormal carbon monoxide diffusion capacity in COVID-19 patients. Eur Respir J 2021; 57 (01) 2003263
• 30 Huang C, Huang L, Wang Y. et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021; 397 (10270): 220-232