Effect of heparin treatment on pulmonary embolism and in-hospital death in unvaccinated COVID-19 patients without overt deep vein thrombosis.

Anticoagulant D-dimer Multi-state model Retrospective study Survival analysis

Journal

Thrombosis journal
ISSN: 1477-9560
Titre abrégé: Thromb J
Pays: England
ID NLM: 101170542

Informations de publication

Date de publication:
20 Jun 2022
Historique:
received: 19 02 2022
accepted: 09 06 2022
entrez: 20 6 2022
pubmed: 21 6 2022
medline: 21 6 2022
Statut: epublish

Résumé

Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT. Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated. Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis. PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity.

Sections du résumé

BACKGROUND BACKGROUND
Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT.
METHODS METHODS
Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated.
RESULTS RESULTS
Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis.
CONCLUSIONS CONCLUSIONS
PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity.

Identifiants

pubmed: 35725464
doi: 10.1186/s12959-022-00393-z
pii: 10.1186/s12959-022-00393-z
pmc: PMC9207168
doi:

Types de publication

Journal Article

Langues

eng

Pagination

34

Informations de copyright

© 2022. The Author(s).

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Auteurs

Bruno Bais (B)

Thrombosis Prevention Unit, Division of Internal Medicine, Academic Hospital of Udine (ASUFC), 33100, Udine, UD, Italy.

Emanuela Sozio (E)

Infectious Diseases Clinic, Department of Medicine, University of Udine, 33100, Udine, Italy.

Daniele De Silvestri (D)

Thrombosis Prevention Unit, Division of Internal Medicine, Academic Hospital of Udine (ASUFC), 33100, Udine, UD, Italy.

Stefano Volpetti (S)

Hematology and Bone Marrow Transplantation, Department of Medicine, University of Udine, 33100, Udine, Italy.

Maria Elena Zannier (ME)

Hematology and Bone Marrow Transplantation, Department of Medicine, University of Udine, 33100, Udine, Italy.

Carla Filì (C)

Hematology and Bone Marrow Transplantation, Department of Medicine, University of Udine, 33100, Udine, Italy.

Flavio Bassi (F)

Department of Anesthesia and Intensive Care Medicine, Academic Hospital of Udine (ASUFC), 33100, Udine, Italy.

Lucia Alcaro (L)

Internal Medicine, Department of Medicine, University of Udine, 33100, Udine, Italy.

Marco Cotrufo (M)

Infectious Diseases Clinic, Department of Medicine, University of Udine, 33100, Udine, Italy.

Alberto Pagotto (A)

Infectious Diseases Clinic, Department of Medicine, University of Udine, 33100, Udine, Italy.

Alessandro Giacinta (A)

Infectious Diseases Clinic, Department of Medicine, University of Udine, 33100, Udine, Italy.

Vincenzo Patruno (V)

Division of Pulmonary Medicine, Academic Hospital of Udine (ASUFC), 33100, Udine, Italy.

Andrea Da Porto (A)

Internal Medicine, Department of Medicine, University of Udine, 33100, Udine, Italy.

Rodolfo Sbrojavacca (R)

Infectious Diseases Clinic, Department of Medicine, University of Udine, 33100, Udine, Italy.

Francesco Curcio (F)

Department of Laboratory Medicine, University of Udine, 33100, Udine, Italy.

Carlo Tascini (C)

Infectious Diseases Clinic, Department of Medicine, University of Udine, 33100, Udine, Italy.

Leonardo Alberto Sechi (LA)

Internal Medicine, Department of Medicine, University of Udine, 33100, Udine, Italy.

GianLuca Colussi (G)

Internal Medicine, Department of Medicine, University of Udine, 33100, Udine, Italy. gianluca.colussi@uniud.it.

Classifications MeSH