Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With COVID-19 Pneumonia

Charles Tacquard, Alexandre Mansour, Alexandre Godon, Julien Godet, Julien Poissy, Delphine Garrigue, Eric Kipnis, Sophie Rym Hamada, Paul Michel Mertes, Annick Steib, Mathilde Ulliel-Roche, Bélaïd Bouhemad, Maxime Nguyen, Florian Reizine, Isabelle Gouin-Thibault, Marie Charlotte Besse, Nived Collercandy, Stefan Mankikian, Jerrold H Levy, Yves Gruel, Pierre Albaladejo, Sophie Susen, Anne Godier, French Working Group on Perioperative Hemostasis, P Albaladejo, N Blais, F Bonhomme, A Borel-Derlon, A Cohen, J-P Collet, E de Maistre, P Fontana, D Garrigue Huet, A Godier, Y Gruel, A Godon, B Ickx, S Laporte, D Lasne, J Llau, G Le Gal, T Lecompte, S Lessire, J H Levy, D Longrois, S Madi-Jebara, A Mansour, M Mazighi, P Mismetti, P E Morange, S Motte, F Mullier, N Nathan, P Nguyen, G Pernod, N Rosencher, S Roullet, P M Roy, S Schlumberger, P Sié, A Steib, S Susen, C A Tacquard, S Testa, A Vincentelli, P Zufferey, Charles Tacquard, Alexandre Mansour, Alexandre Godon, Julien Godet, Julien Poissy, Delphine Garrigue, Eric Kipnis, Sophie Rym Hamada, Paul Michel Mertes, Annick Steib, Mathilde Ulliel-Roche, Bélaïd Bouhemad, Maxime Nguyen, Florian Reizine, Isabelle Gouin-Thibault, Marie Charlotte Besse, Nived Collercandy, Stefan Mankikian, Jerrold H Levy, Yves Gruel, Pierre Albaladejo, Sophie Susen, Anne Godier, French Working Group on Perioperative Hemostasis, P Albaladejo, N Blais, F Bonhomme, A Borel-Derlon, A Cohen, J-P Collet, E de Maistre, P Fontana, D Garrigue Huet, A Godier, Y Gruel, A Godon, B Ickx, S Laporte, D Lasne, J Llau, G Le Gal, T Lecompte, S Lessire, J H Levy, D Longrois, S Madi-Jebara, A Mansour, M Mazighi, P Mismetti, P E Morange, S Motte, F Mullier, N Nathan, P Nguyen, G Pernod, N Rosencher, S Roullet, P M Roy, S Schlumberger, P Sié, A Steib, S Susen, C A Tacquard, S Testa, A Vincentelli, P Zufferey

Abstract

Background: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.

Research question: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?

Study design and methods: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.

Results: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).

Interpretation: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.

Trial registry: ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov.

Keywords: COVID-19; anticoagulation; bleeding; thrombosis.

Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Diagram showing retrospective classification of the level of anticoagulation for thromboprophylaxis. This algorithm was used at each time point to classify the patient into either standard or high-dose prophylactic anticoagulation. A patient could change category between two time points several times during the study period. LWMH = low-molecular-weight heparin; UFH = unfractionated heparin.

References

    1. Al-Ani F., Chehade S., Lazo-Langner A. Thrombosis risk associated with COVID-19 infection. A scoping review. Thromb Res. 2020;192:152–160.
    1. Klok F.A., Kruip M.J.H.A., van der Meer N.J.M. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145–147.
    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;18(6):1421–1424.
    1. Middeldorp S., Coppens M., Haaps TF van. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020;18:1995–2002.
    1. Helms J., Tacquard C., Severac F. High risk of thrombosis in patients in severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089–1098.
    1. Rosovsky R.P., Sanfilippo K.M., Wang T.F. Anticoagulation practice patterns in COVID-19: a global survey. Res Pract Thromb Haemost. 2020;4(6):969–983.
    1. Susen S., Tacquard C.A., Godon A. Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring. Crit Care. 2020;24(1):364.
    1. Poissy J., Goutay J., Caplan M. Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence. Circulation. 2020;142:184–186.
    1. Rocca B., Fox K.A.A., Ajjan R.A. Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis. Eur Heart J. 2018;39(19):1672–1686f.
    1. 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(4):692–694.
    1. Grafféo N., Castell F., Belot A., Giorgi R. A log-rank-type test to compare net survival distributions: a test to compare net survival distributions. Biometrics. 2016;72(3):760–769.
    1. van der Wal W.M., Geskus R.B. Ipw: an R package for inverse probability weighting. J Stat Soft. 2011;43(13):1–23.
    1. Bilaloglu S., Aphinyanaphongs Y., Jones S., Iturrate E., Hochman J., Berger J.S. Thrombosis in hospitalized patients with COVID-19 in a New York City health system. JAMA. 2020;324(8):799.
    1. Paranjpe I., Fuster V., Lala A. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol. 2020;76(1):122–124.
    1. Paolisso P., Bergamaschi L., D’Angelo E.C. Preliminary experience with low molecular weight heparin strategy in COVID-19 patients. Front Pharmacol. 2020;11:1124.
    1. Zhang L., Feng X., Zhang D. Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome. Circulation. 2020;142(2):114–128.
    1. Seidu S, Gillies C, Zaccardi F, et al. The impact of obesity on severe disease and mortality in people with SARS-CoV-2: a systematic review and meta-analysis. Endocrinol Diab Metab. In press.
    1. Hsu A., Liu Y., Zayac A.S., Olszewski A.J., Reagan J.L. Intensity of anticoagulation and survival in patients hospitalized with COVID-19 pneumonia. Thromb Res. 2020;196:375–378.
    1. Ionescu F., Jaiyesimi I., Petrescu I. Association of anticoagulation dose and survival in hospitalized COVID-19 patients: a retrospective propensity score-weighted analysis. Eur J Haematol. 2021;106(2):165–174.
    1. Atallah B., Sadik Z.G., Salem N. The impact of protocol-based high-intensity pharmacological thromboprophylaxis on thrombotic events in critically ill COVID-19 patients. Anaesthesia. 2021;76:327–335.
    1. Shah A., Donovan K., McHugh A. Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study. Crit Care. 2020;24(1):561.

Source: PubMed

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