Are Current Serum and Plasma Ferritin Cut-offs for Iron Deficiency and Overload Accurate and Reflecting Iron Status? A Systematic Review.

BACKGROUND: Serum or plasma ferritin concentration is recommended by WHO as a biomarker to assess iron status in individuals and populations.
METHODS: A systematic review was undertaken to summarise the evidence for ferritin reflecting iron status and to assess the cut-off points in different populations. Electronic databases were searched for studies evaluating ferritin concentrations compared against bone marrow aspirates for iron deficiency and to liver biopsies for risk of iron overload.
RESULTS: From 18822 records, 298 studies were assessed in full-text, including 72 studies on iron deficiency and 36 on iron overload in the quantitative analysis. All studies were observational. For iron deficiency, the mean ferritin concentration in healthy individuals was 15.1 μg/L (9 studies, 390 participants) when bone marrow iron content was 0, and 70.4 μg/L (3 studies, 151 participants) when bone marrow iron was 1+ or higher. In non-healthy populations, mean ferritin concentrations were 82.43 μg/L for iron depletion (38 studies, 1023 participants) and 381.61 μg/L for iron sufficiency (38 studies, 1549 participants) with wide variations depending on the pathology. For iron overload the results point out to a cut-off close to 500 μg/L although the data was very limited.
CONCLUSION: Ferritin concentration is low in iron deficient individuals and high in iron-loaded individuals, regardless of confounding clinical conditions. Current WHO thresholds for healthy populations appear valid but the data is limited for different age groups or physiological conditions. For iron overload, ferritin concentration would only help in the presumptive diagnosis and guide the need for further assessment.