What is the definition of absolute iron deficiency (ferropenia)?

Definition of Absolute Ferropenia (Iron Deficiency)

Absolute iron deficiency (ferropenia) is defined by depleted iron stores indicated by serum ferritin <100 ng/mL and impaired iron delivery to erythroid marrow evidenced by transferrin saturation (TSAT) <20% in patients with chronic kidney disease, while in otherwise healthy individuals it is defined as serum ferritin <12 ng/mL and TSAT <16%. 1

Diagnostic Thresholds by Population

The definition of absolute ferropenia varies significantly based on clinical context and patient population:

In Chronic Kidney Disease Patients

• Serum ferritin <100 ng/mL 1
• TSAT <20% 1
• These higher thresholds account for the altered iron metabolism in CKD patients receiving erythropoiesis-stimulating agents 1

In Otherwise Healthy Individuals

• Serum ferritin <12 ng/mL 1
• TSAT <16% 1
• More recent evidence suggests ferritin <30 ng/mL is appropriate for healthy males and females aged >15 years 2

In Pediatric Populations

• Children 6-12 years: ferritin <15 µg/L 2
• Adolescents 12-15 years: ferritin <20 µg/L 2
• Adolescents >15 years: ferritin <30 µg/L 2

In Cancer Patients

• Absolute iron deficiency refers to depleted iron stores, primarily due to bleeding 1
• Specific thresholds align with general population values but must be interpreted in context of inflammation 1

Key Distinguishing Features from Functional Iron Deficiency

Absolute iron deficiency represents true depletion of body iron stores, whereas functional iron deficiency occurs when iron stores are adequate but iron cannot be mobilized rapidly enough to meet erythropoietic demands. 1, 3

Laboratory Pattern in Absolute Iron Deficiency:

• Low serum ferritin (reflecting depleted stores) 1
• Low TSAT (reflecting inadequate circulating iron) 1
• Both parameters are concordantly low 1

Laboratory Pattern in Functional Iron Deficiency:

• Normal or elevated serum ferritin (100-700 ng/mL) 1, 3
• Low TSAT (<20%) 1, 3
• Discordant pattern between storage and circulating iron 3

Critical Clinical Considerations

The gold standard for diagnosing absolute iron deficiency is absent stainable bone marrow iron, though this invasive test is rarely performed in clinical practice. 1

Impact of Inflammation:

• Serum ferritin behaves as an acute phase reactant and can be falsely elevated during inflammation 1, 2
• C-reactive protein should be measured to exclude acute phase reaction when interpreting ferritin levels 2
• In inflammatory conditions, higher ferritin thresholds may be needed to diagnose true iron deficiency 4

Combined Assessment:

• The combined interpretation of ferritin and TSAT is essential for accurate diagnosis 1
• This combination distinguishes absolute iron deficiency from functional iron deficiency and inflammatory iron block 1
• High TSAT with high ferritin suggests parenchymal iron loading, which is more toxic than reticuloendothelial iron overload 1

Additional Diagnostic Markers

While ferritin and TSAT are the primary diagnostic tests, supplementary markers include:

• Red cell indices: Increased RDW, decreased MCV and MCH indicate iron-deficient erythropoiesis 1
• Zinc protoporphyrin/heme ratio: Elevated in iron deficiency, useful for screening studies 1
• Soluble transferrin receptor (sTfR): Considerably elevated in iron deficiency anemia, particularly useful when inflammation complicates diagnosis 1