Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis
Main finding · MortalityResult — go to the resultOdds ratio 4.85 95% CI 2.55–9.60Authors' conclusion
These findings establish hyperferritinemic sepsis as a high-risk condition characterized by increased cytokinemia, viral DNAemia, thrombotic microangiopathy, immune depression, macrophage activation syndrome, and death.
Study context
- Population
- Children with sepsis
- Participants
- 117 vs 280
- Exposure
- Hyperferritinemic sepsis vs sepsis without hyperferritinemia
- Hyperferritinemic sepsisn = 117
- Sepsis without hyperferritinemian = 280reference
- Outcome
- Mortality
Methodological detailsmulticentre pediatric research network
- Multicentre pediatric research network
Main finding
As reported in the abstract
Odds ratio
4.85
95% CI 2.55–9.60
P < 0.0001
Events by group
Hyperferritinemic sepsis vs Sepsis without hyperferritinemia
OR 4.85 (95% CI 2.55–9.60); P < 0.0001
Observational data: associations, not effects.
Further findings
Cytokines, biomarkers, viral DNAemia, macrophage activation syndrome (MAS)
- Hyperferritinemic sepsis had higher CRP, sCD163, IL-18, MCP-1/CCL2, IL-6, TNF and other cytokines; lower ADAMTS13 activity, sFasL, ex vivo TNF response to endotoxin and TRAIL; more Adenovirus, BK virus and multiple virus DNAemias; and more MAS (P-value < 0.05)
Causal inference analysis
- Only MCP-1/CCL2, MAS and ferritin levels directly causally associated with mortality
- MCP-1/CCL2 and hyperferritinemia directly causally associated with depressed ex vivo whole blood TNF response to endotoxin
- MCP-1/CCL2 a mediator of MAS; MCP-1/CCL2 and MAS mediators of hyperferritinemia
Original publication
Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis. Crit Care. Published 6 September 2023. doi:10.
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