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Diagnosing Iron Deficiency Is Not Always Straightforward
Bone marrow aspiration with iron staining is the gold standard for diagnosing iron deficiency anemia. However, because it is invasive, clinicians instead usually rely on iron markers, such as serum iron, iron binding capacity, transferrin saturation, ferritin, mean corpuscular volume (MCV), and occasionally, soluble transferrin receptor. To identify the best-performing parameter, investigators retrospectively compared results of these tests and bone marrow aspiration in 6610 patients with hematologic disorders.
Ferritin correlated best with bone marrow iron stores and was superior to transferrin saturation, soluble transferrin receptor, transferrin, hemoglobin, and MCV. A ferritin cutoff of 30 µg/L was highly specific for iron deficiency anemia in men (99%) and women (97%) but poorly sensitive (35% and 54%, respectively). No combination of tests performed better than ferritin alone. The lowest ferritin cutoffs allowing for 95% negative predictive value were 1750 µg/L for women and 4967 µg/L for men.
Comment
When ferritin is low, a diagnosis of iron deficiency is straightforward, although reference ranges vary, and “low” is defined differently across labs and institutions. This study confirms high specificity and positive predictive value when ferritin is below 30 µg/L. Unfortunately, however, there is no feasible ferritin cutoff for ruling out iron deficiency with high negative predictive value.
A common clinical conundrum arises when we try to identify which patients with inflammatory disease — with low transferrin saturation and normal to increased ferritin — have concurrent iron deficiency anemia. Although many hematologists use a ferritin level >100 µg/L as an indicator of sufficient iron stores, the accuracy of this cutoff is unclear. In these cases, we must use clinical judgement based on risk factors for iron deficiency (e.g., bleeding, malabsorption) and less-utilized tests (soluble transferrin receptor), which unfortunately can underperform.
Citation(s)
Author:
Lahtiharju T et al.
Title:
Ferritin outperforms other biomarkers in predicting bone marrow iron stores in patients with hematologic disorders.
Source:
Blood Adv
2025
Apr
8; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Brady L. Stein, MD, MHS