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Suspecting Hyperferritinemic Sepsis in Iron-Deficient Population: Do We Need a Lower Plasma Ferritin Threshold?
Swarup Ghosh1, Arun K Baranwal2, Prateek Bhatia1
1Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Insights
In iron-deficient children with septic shock, plasma ferritin levels rise significantly, correlating with inflammation and organ dysfunction. Elevated ferritin may predict higher mortality, suggesting a need to re-evaluate diagnostic thresholds.
Area of Science:
- Pediatric critical care medicine
- Hematology
- Infectious diseases
Background:
- Hyperferritinemia is a potential biomarker for sepsis-induced macrophage activation syndrome.
- Data on ferritin in iron-deficient children with sepsis is limited.
- This study investigates plasma ferritin behavior in iron-deficient children with septic shock.
Purpose of the Study:
- To explore plasma ferritin behavior in children with septic shock and iron deficiency.
- To assess the association between ferritin levels and outcomes in pediatric septic shock.
- To evaluate the utility of ferritin as a biomarker in this specific population.
Main Methods:
- Prospective observational study in a South Asian tertiary care hospital.
- Included 42 children (6 months–12 years) with septic shock and 36 healthy siblings as controls.
- Measured plasma ferritin at enrollment, 1 month post-discharge, and in controls, excluding those with recent transfusions or chronic diseases.
Main Results:
- Septic shock patients exhibited significantly elevated ferritin despite iron deficiency.
- Ferritin levels correlated positively with Pediatric Logistic Organ Dysfunction score and C-reactive protein.
- Elevated ferritin (≥500 or ≥1,000 ng/mL) was associated with increased mortality risk, though not independently.
- Follow-up ferritin in survivors decreased significantly but remained higher than controls.
Conclusions:
- Plasma ferritin rises significantly in pediatric septic shock, even with iron deficiency, indicating inflammation and organ dysfunction.
- Lower ferritin thresholds (500 or 1,000 ng/mL) may predict higher mortality in this group.
- Re-evaluation of ferritin thresholds for hyperferritinemic sepsis and macrophage activation syndrome in iron-deficient children is warranted.
- Further research with frequent ferritin measurements is needed to validate these findings.
Objectives:
Hyperferritinemia is being suggested to identify patients with sepsis-induced macrophage activation syndrome for early intervention. However, data among iron-deficient children are scarce. This study was planned to explore the biological behavior of plasma ferritin in children from communities with a high frequency of iron deficiency with septic shock and its association with the outcome.
Design:
Prospective observational study.
Setting:
Tertiary care teaching hospital in a low-middle income economy of South Asia.
Patients Or Subjects:
Patients (6 mo to 12 yr) (n = 42) with septic shock and their healthy siblings as controls (n = 36). Patients/controls with blood transfusion/iron supplement during last 6 months or with any chronic disease were excluded.
Interventions:
None.
Measurements And Main Results:
Ferritin was measured in patients at enrollment and then at 1 month of hospital discharge while they were not on iron supplementation and in controls as indicative of baseline level. Patients' median age was 30 months (13.5-87 mo), 31% were malnourished, majority (86%) had anemia, and two thirds had microcytic hypochromic red cells. Ferritin at admission was 763 ng/mL (480-1,820 ng/mL) in nonsurvivors, whereas 415 ng/mL (262-852 ng/mL) in survivors (p = 0.11). Pediatric Logistic Organ Dysfunction score and C-reactive protein correlated positively with plasma ferritin (p = 0.03 and p = 0.01, respectively) at enrollment. Elevated ferritin of greater than 500 ng/mL (relative risk, 2.48; 95% CI, 0.95-6.43) and greater than 1,000 ng/mL (relative risk, 1.94; 95% CI, 0.94-4.02) were associated with higher mortality but not independently. Among survivors, the 1-month follow-up ferritin fell significantly to 97 ng/mL (16-118 ng/mL) (p = 0.001). However, it was still significantly higher than that in sibling controls (19 ng/mL [10-54 ng/mL]) (p = 0.003).
Conclusions:
Ferritin rises significantly in septic shock patients despite iron deficiency and seems to correlate with the severity of inflammation and organ dysfunction. Even a lower threshold (of 500 or 1,000 ng/mL) could predict higher mortality. It may suggest the need for redefining the plasma ferritin threshold for suspecting hyperferritinemic sepsis and sepsis-induced macrophage activation syndrome in these patients. Larger studies with frequent ferritin measurements are desirable to validate these initial observations.
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