Suspecting Hyperferritinemic Sepsis in Iron-Deficient Population: Do We Need a Lower Plasma Ferritin Threshold?

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. This study was performed at Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: baranwal1970@gmail.com ©2018The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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