Observational Study

. 2021 Jun;159(6):2417-2427.

doi: 10.1016/j.chest.2021.01.017. Epub 2021 Jan 16.

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

Charles Tacquard¹, Alexandre Mansour², Alexandre Godon³, Julien Godet⁴, Julien Poissy⁵, Delphine Garrigue⁶, Eric Kipnis⁷, Sophie Rym Hamada⁸, Paul Michel Mertes¹, Annick Steib¹, Mathilde Ulliel-Roche³, Bélaïd Bouhemad⁹, Maxime Nguyen⁹, Florian Reizine¹⁰, Isabelle Gouin-Thibault¹¹, Marie Charlotte Besse¹², Nived Collercandy¹², Stefan Mankikian¹², Jerrold H Levy¹³, Yves Gruel¹⁴, Pierre Albaladejo³, Sophie Susen¹⁵, Anne Godier⁸; French Working Group on Perioperative Hemostasis

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ Department of Anesthesiology and Intensive Care, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
² Department of Anesthesiology Critical Care Medicine and Perioperative Medicine, CHU de Rennes, Rennes, France.
³ Department of Anesthesiology and Critical Care, Grenoble Alpes University Hospital, Grenoble, France.
⁴ Groupe Méthodes en Recherche Clinique, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
⁵ University of Lille, Inserm U1285, CHU Lille, Pôle de Réanimation, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
⁶ Department of Anesthesiology and Critical Care, Surgical Critical Care, Centre Hospitalier Universitaire Lille, Lille, France.
⁷ University of Lille, CNRS, Inserm, CHU Lille, Surgical Critical Care, Department of Anesthesiology and Critical Care, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, Lille, France.
⁸ Department of Anesthesiology and Critical Care, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris University, Paris, France.
⁹ Department of Anesthesiology and Intensive Care, Dijon University Hospital and University of Burgundy, Lipness Team, INSERM Research Center LNC-UMR1231 and LabExLipSTIC, Dijon, France.
¹⁰ Service des Maladies Infectieuses et Réanimation Médicale, Rennes University Hospital, Rennes, France.
¹¹ Department of Hematology-Hemostasis, Rennes University Hospital, Rennes, France.
¹² Service de Médecine Intensive-Réanimation, CHU de Tours, Tours, France.
¹³ Departments of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC.
¹⁴ Department of Hematology-Hemostasis, Tours University Hospital, Tours, France.
¹⁵ Hemostasis Department, Heart and Lung Institute, CHU Lille, Lille, France. Electronic address: sophiesusen@aol.com.

PMID: 33465342
PMCID: PMC7832130
DOI: 10.1016/j.chest.2021.01.017

Observational Study

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

Charles Tacquard et al. Chest. 2021 Jun.

. 2021 Jun;159(6):2417-2427.

doi: 10.1016/j.chest.2021.01.017. Epub 2021 Jan 16.

Authors

Collaborators

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

Affiliations

¹ Department of Anesthesiology and Intensive Care, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
² Department of Anesthesiology Critical Care Medicine and Perioperative Medicine, CHU de Rennes, Rennes, France.
³ Department of Anesthesiology and Critical Care, Grenoble Alpes University Hospital, Grenoble, France.
⁴ Groupe Méthodes en Recherche Clinique, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
⁵ University of Lille, Inserm U1285, CHU Lille, Pôle de Réanimation, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
⁶ Department of Anesthesiology and Critical Care, Surgical Critical Care, Centre Hospitalier Universitaire Lille, Lille, France.
⁷ University of Lille, CNRS, Inserm, CHU Lille, Surgical Critical Care, Department of Anesthesiology and Critical Care, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, Lille, France.
⁸ Department of Anesthesiology and Critical Care, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris University, Paris, France.
⁹ Department of Anesthesiology and Intensive Care, Dijon University Hospital and University of Burgundy, Lipness Team, INSERM Research Center LNC-UMR1231 and LabExLipSTIC, Dijon, France.
¹⁰ Service des Maladies Infectieuses et Réanimation Médicale, Rennes University Hospital, Rennes, France.
¹¹ Department of Hematology-Hemostasis, Rennes University Hospital, Rennes, France.
¹² Service de Médecine Intensive-Réanimation, CHU de Tours, Tours, France.
¹³ Departments of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC.
¹⁴ Department of Hematology-Hemostasis, Tours University Hospital, Tours, France.
¹⁵ Hemostasis Department, Heart and Lung Institute, CHU Lille, Lille, France. Electronic address: sophiesusen@aol.com.

PMID: 33465342
PMCID: PMC7832130
DOI: 10.1016/j.chest.2021.01.017

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.

PubMed Disclaimer

Figures

**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.

See this image and copyright information in PMC

Comment in

Clotting and COVID-19.
Bull TM. Bull TM. Chest. 2021 Jun;159(6):2151-2152. doi: 10.1016/j.chest.2021.02.067. Chest. 2021. PMID: 34099126 Free PMC article. No abstract available.
High-Dose Prophylactic Anticoagulation in Severe COVID-19 Pneumonia.
Nadeem R, Kamat S. Nadeem R, et al. Chest. 2021 Jul;160(1):e94-e95. doi: 10.1016/j.chest.2021.02.036. Chest. 2021. PMID: 34246406 Free PMC article. No abstract available.
Response.
Tacquard C, Godon A, Mansour A, Gruel Y, Susen S, Godier A. Tacquard C, et al. Chest. 2021 Jul;160(1):e95-e96. doi: 10.1016/j.chest.2021.02.035. Chest. 2021. PMID: 34246407 Free PMC article. No abstract available.
COVID-19 in the Critically Ill: Too Risky for High-Dose Anticoagulation?
Paez Vargas JJ, Vidal González A, Pérez-Calvo C, Flandes J. Paez Vargas JJ, et al. Chest. 2021 Aug;160(2):e249. doi: 10.1016/j.chest.2021.03.028. Chest. 2021. PMID: 34366058 Free PMC article. No abstract available.
Response.
Tacquard C, Godon A, Mansour A, Gruel Y, Susen S, Godier A. Tacquard C, et al. Chest. 2021 Aug;160(2):e250. doi: 10.1016/j.chest.2021.03.029. Chest. 2021. PMID: 34366060 Free PMC article. No abstract available.

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

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Medical