CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(11): 1888-1898
DOI: 10.1055/a-1768-4371
Stroke, Systemic or Venous Thromboembolism

Adjusting D-dimer to Lung Disease Extent to Exclude Pulmonary Embolism in COVID-19 Patients (Co-LEAD)

Benjamin Planquette*
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
3   Department of Respiratory Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
4   F-CRIN INNOVTE, Saint-Étienne, France
,
Lina Khider*
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
5   Department of Vascular Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
6   Physics for Medicine Paris, INSERM U1273, ESPCI Paris, Paris, France
,
Alice Le Berre**
7   Department of Radiology, Groupe Hospitalier Paris Saint-Joseph, Paris, France
,
Simon Soudet**
8   EA7516 CHIMERE and Service de Médecine Vasculaire, Université Picardie Jules Verne, CHU Amiens-Picardie, Amiens, France
,
Gilles Pernod**
9   Service Universitaire de Médecine Vasculaire, CHU de Grenoble-Alpes, Université Grenoble-Alpes, CNRS/TIMC-IMAG UMR 5525/Thèmas 38043 Grenoble, F-CRIN INNOVTE, Saint-Étienne, France
,
Raphaël Le Mao**
10   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, EA 3878, CIC INSERM 1412, Brest, F-CRIN INNOVTE, Saint-Étienne, France
,
Matthieu Besutti**
11   Department of Cardiology, University Hospital, Besançon, EA3920, University of Burgundy Franche Comté, Besançon, France
,
Nicolas Gendron
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
4   F-CRIN INNOVTE, Saint-Étienne, France
12   Department of Haematology, Assistance Publique Hôpitaux de Paris.Centre-Université de Paris (APHP-CUP), Paris, France
,
Alexandra Yanoutsos
13   Department of vascular medicine, Groupe hospitalier Paris Saint Joseph, Paris, France
14   Department of Vascular Medicine, INSERM CRESS UMR 1153, Paris, France
,
David M. Smadja
15   Department of Radiology, Université de Paris, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
,
Guillaume Goudot
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
5   Department of Vascular Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
6   Physics for Medicine Paris, INSERM U1273, ESPCI Paris, Paris, France
,
Salma Al Kahf
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
3   Department of Respiratory Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
4   F-CRIN INNOVTE, Saint-Étienne, France
,
Nassim Mohamedi
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
5   Department of Vascular Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
6   Physics for Medicine Paris, INSERM U1273, ESPCI Paris, Paris, France
,
Antoine Al Hamoud
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
3   Department of Respiratory Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
4   F-CRIN INNOVTE, Saint-Étienne, France
,
Aurélien Philippe
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
4   F-CRIN INNOVTE, Saint-Étienne, France
12   Department of Haematology, Assistance Publique Hôpitaux de Paris.Centre-Université de Paris (APHP-CUP), Paris, France
,
Laure Fournier
15   Department of Radiology, Université de Paris, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
,
Bastien Rance
16   Department of Medical Informatics, Université de Paris, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
,
Jean-Luc Diehl
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
17   Intensive Care Unit, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
,
Tristan Mirault
5   Department of Vascular Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
19   Department of Emergency, Université de Paris, PARCC, INSERM, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
,
Emmanuel Messas
5   Department of Vascular Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
7   Department of Radiology, Groupe Hospitalier Paris Saint-Joseph, Paris, France
18   Department of Vascular Medicine, Paris Research Cardiovascular Center, PARCC, INSERM UMR-S 970, Paris, France
,
Joseph Emmerich
13   Department of vascular medicine, Groupe hospitalier Paris Saint Joseph, Paris, France
14   Department of Vascular Medicine, INSERM CRESS UMR 1153, Paris, France
,
Richard Chocron
19   Department of Emergency, Université de Paris, PARCC, INSERM, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
,
Francis Couturaud
10   Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, Université de Bretagne Occidentale, EA 3878, CIC INSERM 1412, Brest, F-CRIN INNOVTE, Saint-Étienne, France
,
Gilbert Ferretti
20   Department of Radiology, CHU, Université Grenoble-Alpes, Saint-Étienne, France
,
Marie Antoinette Sevestre
8   EA7516 CHIMERE and Service de Médecine Vasculaire, Université Picardie Jules Verne, CHU Amiens-Picardie, Amiens, France
,
Nicolas Meneveau
11   Department of Cardiology, University Hospital, Besançon, EA3920, University of Burgundy Franche Comté, Besançon, France
,
Gilles Chatellier
21   Department of Statistics, Bioinformatics and Public Health, INSERM CIC 14-18, Paris, France
,
Olivier Sanchez
1   Innovative Therapies in Haemostasis, Université de Paris, INSERM, Paris, France
2   Biosurgical Research Lab (Carpentier Foundation), Université de Paris, Paris, France
3   Department of Respiratory Medicine, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
4   F-CRIN INNOVTE, Saint-Étienne, France
› Author Affiliations
Funding The authors gratefully acknowledge the Assistance Publique – Hopitaux de Paris for their support in bringing this project to life, and the Groupe Hospitalier Paris Saint Joseph for sponsoring it.


Abstract

Objective D-dimer measurement is a safe tool to exclude pulmonary embolism (PE), but its specificity decreases in coronavirus disease 2019 (COVID-19) patients. Our aim was to derive a new algorithm with a specific D-dimer threshold for COVID-19 patients.

Methods We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to extent of lung damage found on computed tomography (CT) was derived in a patient set (n = 337), and its safety assessed in an independent validation set (n = 337).

Results According to receiver operating characteristic curves, in the derivation set, D-dimer safely excluded PE, with one false negative, when using a 900 ng/mL threshold when lung damage extent was <50% and 1,700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm sensitivity was 98.2% (95% confidence interval [CI]: 94.7–100.0) and its specificity 28.4% (95% CI: 24.1–32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI: 0.01–0.44) and the area under the curve (AUC) was 0.63 (95% CI: 0.60–0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI: 88.7–99.6) and 39.2% (95% CI: 32.2–46.1), respectively. The NLR was 0.08 (95% CI; 0.02–0.33), and the AUC did not differ from that of the derivation set (0.68, 95% CI: 0.64–0.72, p = 0.097). Using the Co-LEAD algorithm, 76 among 250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA) and 88 patients would have required two CTs.

Conclusion The Co-LEAD algorithm could safely exclude PE, and could reduce the use of CTPA in COVID-19 patients. Further prospective studies need to validate this strategy.

* These two authors contributed equally.


** These five authors contributed equally.


Supplementary Material



Publication History

Received: 31 July 2021

Accepted: 08 February 2022

Accepted Manuscript online:
10 February 2022

Article published online:
17 October 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany