Hemostasis proteins in invasive meningococcal and nonmeningococcal infections: a prospective multicenter study.
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Published version
Author(s)
Type
Journal Article
Abstract
OBJECTIVES: We aimed to describe the variation of hemostasis proteins in children with bacterial infections due to different pathogens (Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus, and group A streptococcus [GAS]) and to study hemostasis proteins in relation to mortality. DESIGN: Preplanned analysis in prospective cohort study. SETTING: Hospitals in five European countries (Austria, The Netherlands, Spain, Switzerland, and the United Kingdom). PATIENTS: Admitted children (2012-2016) with community-acquired infections due to meningococci (n = 83), pneumococci (n = 64), S. aureus (n = 50), and GAS (n = 44) with available serum samples collected less than 48 hours after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fibronectin, plasminogen activator inhibitor type 1 (PAI-1), thrombomodulin, and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) were measured in serum in 2019-2020. Additionally, von Willebrand factor, protein C, protein S, and factor IX were measured in citrate plasma available from a subset of patients. Outcome measures included in-hospital mortality and disease severity (need for ventilation/inotropes, Pediatric Index of Mortality score). Of 241 children, 21 (8.7%) died and 177 (73.5%) were admitted to PICU. Mortality rate was similar for the pathogen groups. Levels of fibronectin and thrombomodulin differed for the different pathogens (p < 0.05). Fibronectin levels were lower in GAS infections than in S. pneumoniae and S. aureus infections but did not differ from meningococcal infections. Thrombomodulin levels in meningococcal infections were higher than in S. aureus and pneumococcal infections. Overall, the area under the curve for mortality was 0.81 (95% CI, 0.70-0.92) for thrombomodulin and 0.78 (95% CI, 0.69-0.88) for ADAMTS-13. The association of each hemostasis protein did not vary across pathogens for any of the outcome measures. CONCLUSIONS: Hemostatic disturbances in childhood bacterial infections are not limited to meningococcal sepsis but occur with a comparable severity across nonmeningococcal infections. High thrombomodulin and high ADAMTS-13 had good discriminative ability for mortality. Our results emphasize the importance of hemostatic disturbances in meningococcal and nonmeningococcal pediatric bacterial infections.
Date Issued
2022-12
Online Publication Date
2022-09-12T10:39:28Z
Date Acceptance
2022-08-01
ISSN
1529-7535
Publisher
Lippincott, Williams & Wilkins
Start Page
e543
End Page
e554
Journal / Book Title
Pediatric Critical Care Medicine
Volume
23
Issue
12
Copyright Statement
© 2022 The Author(s).
Published by Wolters Kluwer Health,
Inc. on behalf of the Society of
Critical Care Medicine and the World
Federation of Pediatric Intensive
and Critical Care Societies. This
is an open-access article distributed under the terms of the
Creative Commons Attribution-Non
Commercial-No Derivatives License
4.0 (CCBY-NC-ND), where it is permissible to download and share the
work provided it is properly cited. The
work cannot be changed in any way
or used commercially without permission from the journal.
Published by Wolters Kluwer Health,
Inc. on behalf of the Society of
Critical Care Medicine and the World
Federation of Pediatric Intensive
and Critical Care Societies. This
is an open-access article distributed under the terms of the
Creative Commons Attribution-Non
Commercial-No Derivatives License
4.0 (CCBY-NC-ND), where it is permissible to download and share the
work provided it is properly cited. The
work cannot be changed in any way
or used commercially without permission from the journal.
Sponsor
European Commission
Identifier
https://journals.lww.com/pccmjournal/Fulltext/9900/Hemostasis_Proteins_in_Invasive_Meningococcal_and.76.aspx
https://www.ncbi.nlm.nih.gov/pubmed/36044313
00130478-990000000-00076
Grant Number
279185
Subjects
European Union Childhood Life-threatening Infectious Disease (EUCLIDS) Consortium
Pediatrics
1110 Nursing
1114 Paediatrics and Reproductive Medicine
Publication Status
Published
Country
United States
Date Publish Online
2022-12