An Exploratory Analysis of Routine Ferritin Measurement Upon Admission and the Prognostic Implications of Low-Grade Ferritinemia During Inflammation

Abstract

Serum ferritin is usually measured in the presence of anemia or in suspected iron overload syndromes. Ferritin is also an acute-phase protein that is elevated during systemic inflammation. However, the prognostic value of routinely measuring ferritin upon admission to a medical facility is not clear. Therefore, we examined the association between ferritin concentrations measured at the time of hospital admission with 30-day and long-term mortality. We obtained routine ferritin measurements taken within 24 hours of admission in 2859 patients hospitalized in an internal medicine department. Multiple clinical and laboratory parameters were used to assess the association between ferritin and overall mortality during a median follow-up of 15 months (interquartile range [IQR] 8-22). Ferritin levels were associated with increased 30-day mortality rates (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.03-1.06) for each 100 ng/mL increase. Patients with intermediate (78-220 ng/mL) and high (>221 ng/mL) ferritin concentrations (2nd and 3rd tertiles) had higher 30-day mortality rates even after adjustment for age, sex, and existing comorbidities (OR 2.05, 95% CI 1.70-2.5). Long-term overall mortality rates demonstrated a similar pattern across ferritin tertiles (hazard ratio [HR] 1.54, 95% CI 1.39-1.71). Routine admission ferritin concentrations are linearly and independently correlated with excess mortality risk in hospitalized patients, even those with apparently "normal" ferritin concentrations (<300 mg/mL). Thus, low-grade ferritinemia might not be an innocent finding in the context of the inflammatory response. Its potential biological and therapeutic implications warrant future research.