Top

Published in:

Open Access 01-04-2021 | Venous Thrombosis

Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review

Authors: William J. Jenner, Rahim Kanji, Saeed Mirsadraee, Ying X. Gue, Susanna Price, Sanjay Prasad, Diana A. Gorog

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2021

Abstract

A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.

Available only for authorised users

Tang N, Li D, Wang X, Sun Z (2020) Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 18:844–847. https://doi.org/10.1111/jth.14768CrossRefPubMedPubMedCentral

(2020) Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19)

Remuzzi A, Remuzzi G (2020) COVID-19 and Italy: what next? Heal Policy www.thelancet.com 395:1225–1228. https://doi.org/https://doi.org/10.1016/S0140-6736(20)30627-9

Grasselli G, Pesenti A, Cecconi M (2020) Critical care utilization for the COVID-19 outbreak in lombardy, italy: early experience and forecast during an emergency response. JAMA 323:1545–1546. https://doi.org/10.1001/jama.2020.4031CrossRefPubMed

Docherty AB, Harrison EM, Green CA et al (2020) Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study. BMJ 369:m1985. https://doi.org/10.1136/bmj.m1985CrossRefPubMedPubMedCentral

Richardson S, Hirsch JS, Narasimhan M et al (2020) Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 323:2052–2059. https://doi.org/10.1001/jama.2020.6775CrossRefPubMedPubMedCentral

Moores LK, Tritschler T, Brosnahan S et al (2020) Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report. Chest 158:1143–1163. https://doi.org/10.1016/j.chest.2020.05.559CrossRefPubMed

Spyropoulos AC, Levy JH, Ageno W et al (2020) Scientific and standardization committee communication: clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 18:1859–1865. https://doi.org/10.1111/jth.14929CrossRefPubMed

Bikdeli B, Madhavan MV, Jimenez D et al (2020) COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 75:2950–2973. https://doi.org/10.1016/j.jacc.2020.04.031CrossRefPubMedPubMedCentral

10.

Klok FA, Kruip MJHA, van der Meer NJM et al (2020) Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 191:145–147. https://doi.org/10.1016/J.THROMRES.2020.04.013CrossRefPubMedPubMedCentral

11.

Di Minno A, Ambrosino P, Calcaterra I, Di Minno MND (2020) COVID-19 and venous thromboembolism: a meta-analysis of literature studies. Semin Thromb Hemost 46:763–771. https://doi.org/10.1055/s-0040-1715456CrossRefPubMedPubMedCentral

12.

Al-Ani F, Chehade S, Lazo-Langner A (2020) Thrombosis risk associated with COVID-19 infection. A scoping review Thromb Res 192:152–160. https://doi.org/10.1016/j.thromres.2020.05.039CrossRefPubMed

13.

Chi G, Lee JJ, Jamil A et al (2020) Venous thromboembolism among hospitalized patients with COVID-19 undergoing thromboprophylaxis: a systematic review and meta-analysis. J Clin Med 9:2489. https://doi.org/10.3390/jcm9082489CrossRefPubMedCentral

14.

Wang C, Zhang H, Zhou M, et al (2020) Prognosis of COVID-19 in patients with vein thrombosis: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 24:10279–10285. https://doi.org/https://doi.org/10.26355/eurrev_202010_23252

15.

Porfidia A, Valeriani E, Pola R et al (2020) Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis. Thromb Res 196:67–74. https://doi.org/10.1016/j.thromres.2020.08.020CrossRefPubMedPubMedCentral

16.

Roncon L, Zuin M, Barco S et al (2020) Incidence of acute pulmonary embolism in COVID-19 patients: systematic review and meta-analysis. Eur J Intern Med. https://doi.org/10.1016/j.ejim.2020.09.006CrossRefPubMedPubMedCentral

17.

Jiménez D, García-Sanchez A, Rali P et al (2020) Incidence of VTE and bleeding among hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis. Chest. https://doi.org/10.1016/j.chest.2020.11.005CrossRefPubMedPubMedCentral

18.

Higgins J, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0

19.

McInnes MDF, Moher D, Thombs BD et al (2018) Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement. JAMA 319:388–396. https://doi.org/10.1001/jama.2017.19163CrossRefPubMed

20.

Sterne JA, Hernán MA, Reeves BC, et al (2016) The Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) assessment tool

21.

Klok FA, Kruip MJHA, van der Meer NJM et al (2020) Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res 191:148–150. https://doi.org/10.1016/J.THROMRES.2020.04.041CrossRefPubMedPubMedCentral

22.

Longchamp A, Longchamp J, Manzocchi-Besson S et al (2020) Venous thromboembolism in critically Ill patients with COVID-19: Results of a screening study for deep vein thrombosis. Res Pract Thromb Haemost 4:842–847. https://doi.org/10.1002/rth2.12376CrossRefPubMedPubMedCentral

23.

Mak SM, Mak D, Hodson D et al (2020) Pulmonary ischaemia without pulmonary arterial thrombus in COVID-19 patients receiving extracorporeal membrane oxygenation: a cohort study. Clin Radiol 75:795.e1-795.e5. https://doi.org/10.1016/j.crad.2020.07.006CrossRef

24.

Parzy G, Daviet F, Puech B et al (2020) Venous thromboembolism events following venovenous extracorporeal membrane oxygenation for severe acute respiratory syndrome coronavirus 2 based on CT scans. Crit Care Med 48:e971–e975. https://doi.org/10.1097/CCM.0000000000004504CrossRefPubMed

25.

Nahum J, Morichau-Beauchant T, Daviaud F et al (2020) Venous thrombosis among critically Ill patients with coronavirus disease 2019 (COVID-19). JAMA Netw Open 3:e2010478. https://doi.org/10.1001/jamanetworkopen.2020.10478CrossRefPubMedPubMedCentral

26.

Llitjos J-F, Leclerc M, Chochois C et al (2020) High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 18:1743–1746. https://doi.org/10.1111/jth.14869CrossRefPubMed

27.

Voicu S, Delrue M, Chousterman B et al (2020) Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications. Eur Rev Med Pharmacol Sci 27:9161–9168

28.

Ren B, Yan F, Deng Z et al (2020) Extremely high incidence of lower extremity deep venous thrombosis in 48 patients with severe COVID-19 in Wuhan. Circulation 142:181–183. https://doi.org/10.1161/CIRCULATIONAHA.120.047407CrossRefPubMed

29.

Criel M, Falter M, Jaeken J et al (2020) Venous thromboembolism in SARS-CoV-2 patients: only a problem in ventilated ICU patients, or is there more to it? Eur Respir J. https://doi.org/10.1183/13993003.01201-2020CrossRefPubMedPubMedCentral

30.

Middeldorp S, Coppens M, van Haaps TF et al (2020) Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 18:1995–2002. https://doi.org/10.1111/jth.14888CrossRefPubMedPubMedCentral

31.

Voicu S, Bonnin P, Stépanian A et al (2020) High prevalence of deep vein thrombosis in mechanically ventilated COVID-19 patients. J Am Coll Cardiol 76:480–482. https://doi.org/10.1016/j.jacc.2020.05.053CrossRefPubMedPubMedCentral

32.

Longhitano Y (2020) Venous thromboembolism in critically ill patients affected by ARDS related to COVID-19 in Northern-West Italy. Eur Rev Med Pharmacol Sci 24:9154–9160PubMed

33.

Cui S, Chen S, Li X et al (2020) Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 18:1421–1424. https://doi.org/10.1111/jth.14830CrossRefPubMed

34.

Poissy J, Goutay J, Caplan M et al (2020) Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence. Circulation 142:184–186. https://doi.org/10.1161/CIRCULATIONAHA.120.047430CrossRefPubMed

35.

Hékimian G, Lebreton G, Bréchot N et al (2020) Severe pulmonary embolism in COVID-19 patients: a call for increased awareness. Crit Care 24:274. https://doi.org/10.1186/s13054-020-02931-5CrossRefPubMedPubMedCentral

36.

Piazza G, Campia U, Hurwitz S et al (2020) Registry of arterial and venous thromboembolic complications in patients with COVID-19. J Am Coll Cardiol 76:2060–2072. https://doi.org/10.1016/j.jacc.2020.08.070CrossRefPubMedPubMedCentral

37.

Thomas W, Varley J, Johnston A et al (2020) Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res 191:76–77. https://doi.org/10.1016/j.thromres.2020.04.028CrossRefPubMedPubMedCentral

38.

Helms J, Tacquard C, Severac F et al (2020) High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 46:1089–1098. https://doi.org/10.1007/s00134-020-06062-xCrossRefPubMedPubMedCentral

39.

Beyls C, Huette P, Abou-Arab O et al (2020) Extracorporeal membrane oxygenation for COVID-19-associated severe acute respiratory distress syndrome and risk of thrombosis. Br J Anaesth. https://doi.org/10.1016/j.bja.2020.04.079CrossRefPubMed

40.

Bemtgen X, Zotzmann V, Benk C et al (2020) Thrombotic circuit complications during venovenous extracorporeal membrane oxygenation in COVID-19. J Thromb Thrombol. https://doi.org/10.1007/s11239-020-02217-1CrossRef

41.

Bilaloglu S, Aphinyanaphongs Y, Jones S et al (2020) Thrombosis in hospitalized patients with COVID-19 in a New York City Health System. JAMA 324:799–801. https://doi.org/10.1001/jama.2020.13372CrossRefPubMedPubMedCentral

42.

Ackermann M, Verleden SE, Kuehnel M et al (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 383:120–128. https://doi.org/10.1056/NEJMoa2015432CrossRefPubMedPubMedCentral

43.

Zhou F, Yu T, Du R et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395:1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3CrossRef

44.

Huang C, Wang Y, Li X et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England) 395:497–506. https://doi.org/10.1016/S0140-6736(20)30183-5CrossRef

45.

Chen N, Zhou M, Dong X et al (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet (London, England) 395:507–513. https://doi.org/10.1016/S0140-6736(20)30211-7CrossRef

46.

Connors JM, Levy JH (2020) COVID-19 and its implications for thrombosis and anticoagulation. Blood 135:2033–2040. https://doi.org/10.1182/blood.2020006000CrossRefPubMed

47.

Thachil J, Tang N, Gando S et al (2020) ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 18:1023–1026. https://doi.org/10.1111/jth.14810CrossRefPubMed

48.

Baumann Kreuziger L, Lee A, Garcia D, et al (2020) COVID-19 and VTE/Anticoagulation: Frequently Asked Questions

49.

Paranjpe I, Fuster V, Lala A et al (2020) Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 76:122–124. https://doi.org/10.1016/j.jacc.2020.05.001CrossRefPubMedPubMedCentral

50.

Ionescu F, Jaiyesimi I, Petrescu I et al (2020) Association of anticoagulation dose and survival in hospitalized COVID-19 patients: A retrospective propensity score-weighted analysis. Eur J Haematol. https://doi.org/10.1111/ejh.13533CrossRefPubMedPubMedCentral

51.

Yuriditsky E, Horowitz JM, Merchan C et al (2020) Thromboelastography profiles of critically Ill patients with coronavirus disease 2019. Crit Care Med 48:1319–1326. https://doi.org/10.1097/CCM.0000000000004471CrossRefPubMed

52.

Shah A, Donovan K, McHugh A et al (2020) Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study. Crit Care 24:561. https://doi.org/10.1186/s13054-020-03260-3CrossRefPubMedPubMedCentral

53.

Lodigiani C, Iapichino G, Carenzo L et al (2020) Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 191:9–14. https://doi.org/10.1016/j.thromres.2020.04.024CrossRefPubMedPubMedCentral

54.

Fraissé M, Logre E, Pajot O et al (2020) Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study. Crit Care 24:275. https://doi.org/10.1186/s13054-020-03025-yCrossRefPubMedPubMedCentral

55.

Al-Samkari H, Karp Leaf RS, Dzik WH et al (2020) COVID and Coagulation: bleeding and thrombotic manifestations of SARS-CoV2 infection. Blood 136:489–500. https://doi.org/10.1182/blood.2020006520CrossRefPubMed

56.

Maatman TK, Jalali F, Feizpour C et al (2020) Routine venous thromboembolism prophylaxis may be inadequate in the hypercoagulable state of severe coronavirus disease 2019. Crit Care Med 48:e783–e790. https://doi.org/10.1097/CCM.0000000000004466CrossRefPubMed

57.

Desborough MJ, Doyle AJ, Griffiths A et al (2020) Image-proven thromboembolism in patients with severe COVID-19 in a tertiary critical care unit in the United Kingdom. Thromb Res 193:1–4. https://doi.org/10.1016/j.thromres.2020.05.049CrossRefPubMedPubMedCentral

58.

Contou D, Pajot O, Cally R et al (2020) Pulmonary embolism or thrombosis in ARDS COVID-19 patients: a French monocenter retrospective study. PLoS ONE 15:e0238413. https://doi.org/10.1371/journal.pone.0238413CrossRefPubMedPubMedCentral

59.

Hippensteel JA, Burnham EL, Jolley SE (2020) Prevalence of venous thromboembolism in critically ill patients with COVID-19. Br J Haematol 190:e126–e156. https://doi.org/10.1111/bjh.16908CrossRef

60.

Avula A, Nalleballe K, Toom S et al (2020) Incidence of thrombotic events and outcomes in COVID-19 patients admitted to intensive care units. Cureus 12:e11079. https://doi.org/10.7759/cureus.11079

61.

de Roquetaillade C, Chousterman BG, Tomasoni D, Zeitouni M, Houdart E, Guedon A, Reiner P, Bordier R, Gayat E, Montalescot G, Metra M, Mebazaa A (2021) Unusual arterial thrombotic events in Covid-19 patients. Int J Cardiol 323:281–284

62.

Hinton J, Mariathas M, Grocott MP, Curzen N (2020) High sensitivity troponin measurement in critical care: flattering to deceive or ‘never means nothing’? J Intensive Care Soc 21(3):232–240

63.

Giustino G, Croft LB, Stefanini GG, Bragato R, Silbiger JJ, Vicenzi M, Danilov T, Kukar N, Shaban N, Kini A, Camaj A, Bienstock SW, Rashed ER, Rahman K, Oates CP, Buckley S, Elbaum LS, Arkonac D, Fiter R, Singh R, Li E, Razuk V, Robinson SE, Miller M, Bier B, Donghi V, Pisaniello M, Mantovani R, Pinto G, Rota I, Baggio S, Chiarito M, Fazzari F, Cusmano I, Curzi M, Ro R, Malick W, Kamran M, Kohli-Seth R, Bassily-Marcus AM, Neibart E, Serrao G, Perk G, Mancini D, Reddy VY, Pinney SP, Dangas G, Blasi F, Sharma SK, Mehran R, Condorelli G, Stone GW, Fuster V, Lerakis S, Goldman ME (2020) Characterization of myocardial injury in patients with COVID-19. J Am Coll Cardiol 76(18):2043–2055

Title: Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review
Authors: William J. Jenner
Rahim Kanji
Saeed Mirsadraee
Ying X. Gue
Susanna Price
Sanjay Prasad
Diana A. Gorog
Publication date: 01-04-2021
Publisher: Springer US
Keywords: Venous Thrombosis
Anticoagulant
Care
COVID-19
Thrombosis
Low Molecular Weight Heparin
Venous Thrombosis
ECMO
ECMO
Published in: Journal of Thrombosis and Thrombolysis / Issue 3/2021
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-021-02394-7

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2021

Biomarkers of platelet activation and cardiovascular risk in the DAPT trial

Ultrastructure of a late-stage bacterial endocarditis valve vegetation

Treatment and outcomes of heparin-induced thrombocytopenia (HIT) in patients with neoplasm, a case series

Stress hyperglycemia is predictive of worse outcome in patients with acute ischemic stroke undergoing intravenous thrombolysis

Should we consider heparin prophylaxis in COVID-19 patients? a systematic review and meta-analysis

Association of ABO blood group type with cardiovascular events in COVID-19

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page