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Hemostasis Proteins in Invasive Meningococcal and Nonmeningococcal Infections: A Prospective Multicenter Study
Nienke N Hagedoorn1, Navin P Boeddha2, Daniela S Kohlfuerst3
1Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Insights
Hemostatic protein levels vary in children with bacterial infections, with thrombomodulin and ADAMTS-13 showing strong predictive value for mortality in both meningococcal and non-meningococcal cases. These findings highlight the critical role of hemostasis in pediatric bacterial infections.
Area of Science:
- Pediatric Infectious Diseases
- Hematology
- Critical Care Medicine
Background:
- Bacterial infections in children can lead to significant hemostatic disturbances.
- Understanding variations in hemostasis proteins across different pathogens is crucial for assessing disease severity and outcomes.
- Previous research has primarily focused on meningococcal sepsis, leaving gaps in knowledge regarding other common pediatric bacterial infections.
Purpose of the Study:
- To investigate the variability of key hemostasis proteins in children with bacterial infections caused by Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus, and group A Streptococcus (GAS).
- To evaluate the association between hemostasis protein levels and in-hospital mortality in pediatric patients with these infections.
- To compare hemostatic protein profiles across different bacterial pathogens.
Main Methods:
- Prospective cohort study involving 241 children admitted with community-acquired bacterial infections across five European countries.
- Measurement of serum fibronectin, plasminogen activator inhibitor type 1 (PAI-1), thrombomodulin, and ADAMTS-13.
- Measurement of plasma von Willebrand factor, protein C, protein S, and factor IX in a subset of patients.
- Analysis of in-hospital mortality, disease severity (ventilation/inotropes), and Pediatric Index of Mortality score.
Main Results:
- Mortality rates were comparable across pathogen groups (8.7% overall).
- Significant differences in fibronectin and thrombomodulin levels were observed between pathogens (p < 0.05).
- Thrombomodulin and ADAMTS-13 demonstrated good discriminative ability for mortality (AUC 0.81 and 0.78, respectively).
Conclusions:
- Hemostatic disturbances are prevalent in pediatric bacterial infections, extending beyond meningococcal sepsis to comparable severity in non-meningococcal infections.
- Elevated levels of thrombomodulin and ADAMTS-13 are significant predictors of mortality in critically ill children with bacterial infections.
- These findings underscore the importance of monitoring hemostasis in managing pediatric bacterial infections, regardless of the causative pathogen.
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.
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