Top

Published in:

Open Access 01-12-2020 | COVID-19 | Research

Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study

Authors: Akshay Shah, Killian Donovan, Anna McHugh, Manish Pandey, Louise Aaron, Charlotte A. Bradbury, Simon J. Stanworth, Raza Alikhan, Stephen Von Kier, Keith Maher, Nicola Curry, Susan Shapiro, Matthew J. Rowland, Matt Thomas, Richard Mason, Matthew Holland, Tom Holmes, Michael Ware, Stefan Gurney, Stuart R. McKechnie

Published in: Critical Care | Issue 1/2020

Abstract

Background

Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications.

Methods

We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications.

Results

A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49–64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not.

Conclusion

Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Graphical abstract

Available only for authorised users

Joly BS, Siguret V, Veyradier A. Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Med. 2020. https://doi.org/10.1007/s00134-020-06088-1.

Mojoli F, Mongodi S, Orlando A, Arisi E, Pozzi M, Civardi L, et al. Our recommendations for acute management of COVID-19. Crit Care. 2020;24:207.CrossRef

Murthy S, Gomersall CD, Fowler RA. Care for critically ill patients with COVID-19. JAMA. 2020;323:1499–500.CrossRef

Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2015432.

Wang Y, Lu X, Chen H, Chen T, Su N, Huang F, et al. Clinical course and outcomes of 344 intensive care patients with COVID-19. Am J Respir Crit Care Med. 2020;201:1430–4.CrossRef

Wang D, Yin Y, Hu C, Liu X, Zhang X, Zhou S, et al. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan. China Crit Care. 2020;24:188.CrossRef

Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020. https://doi.org/10.1007/s00134-020-06062-x.

Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers D, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145–7.CrossRef

Di Micco P, Russo V, Carannante N, Imparato M, Rodolfi S, Cardillo G, et al. Clotting factors in COVID-19: epidemiological association and prognostic values in different clinical presentations in an Italian cohort. J Clin Med. 2020;9:E1371.CrossRef

10.

Llitjos JF, Leclerc M, Chochois C, Monsallier JM, Ramakers M, Auvray M, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14869.

11.

Fraissé M, Logre E, Pajot O, Mentec H, Plantefeve G, Contou D. Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study. Crit Care. 2020;24:275.CrossRef

12.

Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020. https://doi.org/10.1016/j.jacc.2020.04.031.

13.

Spyropoulos AC, Levy JH, Ageno W, Connors JM, Hunt BJ, Iba T, et al. 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. 2020. https://doi.org/10.1111/jth.14929.

14.

Susen S, Tacquard CA, Godon A, Mansour A, Garrigue D, et al. Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring. Crit Care. 2020;24:364.CrossRef

15.

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7.CrossRef

16.

Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2:3257–91.CrossRef

17.

Intensive Care National Audit and Research Centre. COVID-19 report. 2020. https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports. Accessed 24 May 2020.

18.

Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the S, Standardization Committee of the International Society on T, Haemostasis Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients J Thromb Haemost 2005;3:692–694.

19.

Taylor FB, Jr., Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation of the International Society on T, et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–1330.

20.

Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173:489–95.CrossRef

21.

Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5:368–75.CrossRef

22.

Obi AT, Tignanelli CJ, Jacobs BN, Arya S, Park PK, Wakefield TW, et al. Empirical systemic anticoagulation is associated with decreased venous thromboembolism in critically ill influenza A H1N1 acute respiratory distress syndrome patients. J Vasc Surg Venous Lymphat Disord. 2019;7:317–24.CrossRef

23.

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;18:1094–9.CrossRef

24.

Paranjpe I, Fuster V, Lala A, Russak A, Glicksberg BS, Levin MA, et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol. 2020. https://doi.org/10.1016/j.jacc.2020.05.001.

25.

Tremblay D, van Gerwen M, Alsen M, Thibaud S, Kessler AJ, Venugopal S, et al. Impact of anticoagulation prior to COVID-19 infection: a propensity score-matched cohort study. Blood. 2020. https://doi.org/10.1182/blood.2020006941.

26.

Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, van Bentum-Puijk W, et al. The Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia (REMAP-CAP) study: rationale and design. Ann Am Thorac Soc. 2020. https://doi.org/10.1513/AnnalsATS.202003-192SD.

27.

Azouz E, Yang S, Monnier-Cholley L, Arrive L. Systemic arterial thrombosis and acute mesenteric ischemia in a patient with COVID-19. Intensive Care Med. 2020; https://doi.org/10.1007/s00134-020-06079-2.

28.

Griffin DO, Jensen A, Khan M, Chin J, Chin K, Parnell R, et al. Arterial thromboembolic complications in COVID-19 in low-risk patients despite prophylaxis. Br J Haematol. 2020. https://doi.org/10.1111/bjh.16792..

29.

Al-Samkari H, Leaf RK, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, et al. COVID and coagulation: bleeding and thrombotic manifestations of SARS-CoV2 infection. Blood. 2020. https://doi.org/10.1182/blood.2020006520.

30.

Shah A, Stanworth SJ, McKechnie S. Evidence and triggers for the transfusion of blood and blood products. Anaesthesia. 2015;70:e3–5.CrossRef

31.

McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheum. 2020;7:437–45.CrossRef

32.

Wong RSM, Wu A, To KF, Lee N, Lam CWK, Wong CK, et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ. 2003;326:1358–62.CrossRef

33.

Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377:849–62.CrossRef

34.

Kowalewski M, Fina D, Slomka A, Raffa GM, Martucci G, Lo Coco V, et al. COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review. Crit Care. 2020;24(1):205.CrossRef

35.

Leonard-Lorant I, Delabranche X, Severac F, Helms J, Pauzet C, Collange O, et al. Acute pulmonary embolism in COVID-19 patients on CT angiography and relationship to D-dimer levels. Radiology. 2020;201561.

36.

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. https://doi.org/10.1111/jth.14830.

37.

Spahn DR, Bouillon B, Cerny V, Duranteau J, Filipescu D, Hunt BJ, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23:98.CrossRef

38.

Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, et al. Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020; https://doi.org/10.1111/jth.14850.

39.

Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M, et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14854.

40.

Lauzier F, Arnold DM, Rabbat C, Heels-Ansdell D, Zarychanski R, Dodek P, et al. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med. 2013;39:2135–43.CrossRef

Title: Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study
Authors: Akshay Shah
Killian Donovan
Anna McHugh
Manish Pandey
Louise Aaron
Charlotte A. Bradbury
Simon J. Stanworth
Raza Alikhan
Stephen Von Kier
Keith Maher
Nicola Curry
Susan Shapiro
Matthew J. Rowland
Matt Thomas
Richard Mason
Matthew Holland
Tom Holmes
Michael Ware
Stefan Gurney
Stuart R. McKechnie
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: COVID-19
Thrombosis
Heparin
Low Molecular Weight Heparin
Published in: Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/s13054-020-03260-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study

Abstract

Background

Methods

Results

Conclusion

Graphical abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Graphical abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

COVID-19: room for treating T cell exhaustion?

Peritoneal dialysis for COVID-19-associated acute kidney injury

Correction to: International survey on influenza-associated pulmonary aspergillosis (IAPA) in intensive care units: responses suggest low awareness and potential underdiagnosis outside Europe

Could the severity of COVID-19 be increased by low gastric acidity?

Gravitational distribution of regional opening and closing pressures, hysteresis and atelectrauma in ARDS evaluated by electrical impedance tomography

Blocking IL-1 to prevent respiratory failure in COVID-19