Hemostasis Proteins in Invasive Meningococcal and Nonmeningococcal Infections: A Prospective Multicenter Study

Nienke N Hagedoorn*, Navin P Boeddha, Daniela S Kohlfuerst, Suzanne Anderson, Enitan D Carrol, Paul Agapow, Michiel van der Flier, Jan Hazelzet, Jethro Herberg, Taco Kuijpers, Michael Levin, Federico Martinon-Torres, Angelique van Rijswijk, Luregn J Schlapbach, Clementien Vermont, Werner Zenz, Willem A Dik, Gertjan Driessen, Marieke Emonts, EUCLIDS Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)E543-E554
Number of pages12
JournalPediatric critical care medicine
Volume23
Issue number12
Early online date31 Aug 2022
DOIs
Publication statusPublished - Dec 2022

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