New hematology criteria aim to detect early iron depletion in patients

The American Society of Hematology (ASH) has released its 2026 evidence-based guidelines for diagnosing iron deficiency, recommending higher serum ferritin thresholds for several patient populations. Published in the journal Blood Advances, the updated criteria aim to help clinicians identify depleted iron stores earlier, even when hemoglobin levels remain normal.

Why current cutoffs miss deficiencies

Iron deficiency is a leading cause of anemia and can trigger symptoms such as fatigue, irritability, headaches, and restless legs syndrome. Young children, women of reproductive age, and individuals in lower socioeconomic strata face the highest risk. Additional factors include celiac disease, inflammatory bowel disease, prior bariatric surgery, restricted diets, blood loss, heart failure, rheumatologic conditions, and chronic kidney disease.

Deficiency can exist without anemia, yet screening gaps in high-risk groups and inconsistent laboratory reference ranges often lead to underdiagnosis. The ASH panel reviewed systematic evidence up to July 2025 using the GRADE approach, with methodological support from the University of Kansas Health System.

Serum ferritin’s diagnostic role

Ferritin accurately reflects iron status in healthy individuals without inflammation and remains the most widely available indirect measure of total body iron. However, because it is an acute-phase reactant, inflammation can elevate ferritin concentrations despite depleted stores. Consequently, normal or elevated levels do not rule out deficiency in inflamed patients.

The panel debated whether existing thresholds were artificially low due to inclusion of iron-deficient subjects in "healthy" reference populations. They also noted limitations regarding non-standardized results across different laboratory platforms. To address this, the guidelines propose clinically relevant decision-making thresholds rather than relying solely on the lower limit of normal (LLN).

Updated thresholds by patient group

For children aged 9 months to 4 years, the recommended cutoff rises to ≤20 ng/mL from the previous ≤12 ng/mL, assuming no known or suspected inflammation. Evidence supports extending this threshold through adolescence for non-menstruating youths, where <30 ng/mL is suggested.

In adults excluding menstruating or pregnant individuals, the threshold increases to ≤30 ng/mL from ≤15 ng/mL. If signs of deficiency or ongoing risk factors are present, a cutoff of ≤50 ng/mL may apply. For menstruating individuals, ≤30 ng/mL is recommended, though heavy bleeding or abnormal uterine bleeding warrants a higher threshold of ≤50 ng/mL.

Pregnancy recommendations suggest ≤30 ng/mL, strongly advising against the former ≤15 ng/mL standard. Anemia during pregnancy may justify a ≤50 ng/mL threshold. For adults with anemia of inflammation, the guidelines recommend evaluating both serum ferritin and transferrin saturation (TSAT). Deficiency is considered if ferritin is <100 ng/mL or TSAT is <20%.

Implementation and clinical balance

The committee emphasizes that these thresholds guide clinical assessment rather than automatically triggering supplementation. Treatment decisions must weigh underlying causes, patient condition, and potential harms. Raising cutoffs in children risks false positives, unnecessary testing, and iron overload, while adult thresholds must balance overdiagnosis against equitable recognition of deficiency.

Most recommendations rely on low-certainty evidence, with the guidance for anemia of inflammation based on very-low-certainty data. The panel identified research gaps, including the need for prospective studies comparing thresholds and assessing cost-effectiveness. These guidelines will be updated regularly and adapted to local circumstances, serving as tools for policymakers and healthcare providers rather than rigid standards of care.