How is iron deficiency anemia classified and treated?

Classification and Diagnosis of Iron Deficiency Anemia

Iron deficiency anemia is classified using a combination of hemoglobin/hematocrit (to confirm anemia), serum ferritin (to assess iron stores), and transferrin saturation or TIBC (to evaluate iron availability), with interpretation dependent on the presence or absence of inflammation. 1

Diagnostic Approach Based on Inflammation Status

Without Inflammation (No Active Disease)

• Serum ferritin <30 μg/L confirms iron deficiency in patients without clinical, endoscopic, or biochemical evidence of active disease 1
• This threshold provides high specificity (93% in women of childbearing age, 92% in children aged 1-5 years) for ruling out iron deficiency 1
• A serum ferritin <12 μg/L is diagnostic of iron deficiency regardless of other factors 1

With Inflammation (Active Disease Present)

• Serum ferritin up to 100 μg/L may still indicate iron deficiency in the presence of inflammation, as ferritin acts as an acute phase reactant 1
• Transferrin saturation <20% with ferritin >100 μg/L suggests anemia of chronic disease rather than true iron deficiency 1
• Ferritin 30-100 μg/L indicates likely combined iron deficiency and anemia of chronic disease 1

Essential Laboratory Parameters

Complete Blood Count (CBC) Findings

• Hemoglobin and hematocrit are late indicators that only become abnormal after iron stores are depleted, but they remain essential for confirming anemia 1, 2
• Anemia is defined as hemoglobin <5th percentile for age, sex, and pregnancy stage 1
• Microcytic anemia (low MCV) is characteristic but may be absent in combined deficiencies (e.g., concurrent folate deficiency) 1
• Elevated red cell distribution width (RDW) suggests iron deficiency when distinguishing from other causes of microcytosis 1

Iron Studies Beyond Ferritin

• TIBC/transferrin saturation <16-20% supports iron deficiency when ferritin interpretation is unclear 1, 3
• Total iron-binding capacity increases in iron deficiency as the body attempts to capture more circulating iron 1
• Serum iron alone is unreliable due to diurnal variation and should not be used in isolation 1

Critical Diagnostic Pitfalls

Common Misclassification Errors

• CBC parameters alone (hemoglobin, hematocrit, MCV) without iron studies miss early iron deficiency before anemia develops 4
• Individuals may have normal RBC count, hemoglobin, hematocrit, and MCV while having depleted iron stores on ferritin testing 4
• Anemia screening effectiveness has decreased in high-income countries where iron deficiency prevalence is lower, leading to more false positives from other causes 1, 2

Inflammation Confounders

• Ferritin >100 μg/L almost certainly excludes iron deficiency even with inflammation 1
• In inflammatory bowel disease, chronic kidney disease, heart failure, and malignancy, standard ferritin cutoffs are unreliable 1, 3
• CRP, ESR, and leukocyte count should be checked to assess for inflammation when interpreting ferritin 1

Confirmatory Testing When Diagnosis Remains Unclear

• Therapeutic trial of oral iron for 3 weeks with hemoglobin increase >1.0 g/dL confirms iron deficiency retrospectively 1
• Bone marrow aspiration showing absent iron stores is definitive but rarely necessary in clinical practice 1
• Transferrin receptor/ferritin ratio shows promise for distinguishing iron deficiency from anemia of chronic disease but is not yet widely available 1

Classification Algorithm

1. Confirm anemia exists: Check hemoglobin/hematocrit against age/sex-specific cutoffs 1
2. Assess MCV and reticulocyte count: Microcytic with normal/low reticulocytes suggests iron deficiency or chronic disease 1
3. Check inflammatory markers: CRP, ESR to determine which ferritin threshold to apply 1
4. Measure serum ferritin: Use <30 μg/L cutoff without inflammation, <100 μg/L with inflammation 1
5. Add transferrin saturation if ferritin 30-100 μg/L: <20% supports iron deficiency component 1, 3
6. Consider therapeutic trial: If diagnosis uncertain after above workup 1