What are the diagnostic criteria for iron deficiency anemia (IDA) in an adult patient?

Diagnostic Criteria for Iron Deficiency Anemia (IDA)

Iron deficiency anemia is diagnosed when hemoglobin falls below 13 g/dL in men or below 12 g/dL in non-pregnant women, combined with laboratory evidence of iron deficiency—most reliably a serum ferritin <15 μg/L (highly specific) or <30-45 μg/L in clinical practice. 1, 2

Hemoglobin Thresholds for Anemia

The World Health Organization defines anemia as: 1, 2

• Men: Hemoglobin <13.0 g/dL (130 g/L)
• Non-pregnant women: Hemoglobin <12.0 g/dL (120 g/L)
• Pregnant women: Hemoglobin <11.0 g/dL (110 g/L)

While these are standard thresholds, it is reasonable to use your local laboratory's lower limit of normal range to define anemia, as normal ranges vary between populations. 1 However, men with hemoglobin <12 g/dL and postmenopausal women with hemoglobin <10 g/dL should be investigated more urgently, as lower levels suggest more serious underlying disease. 1

Serum Ferritin: The Primary Diagnostic Test

Serum ferritin is the single most specific and powerful test for diagnosing iron deficiency. 1, 2, 3

Ferritin Interpretation Algorithm:

• Ferritin <15 μg/L: Highly specific for iron deficiency (specificity 0.99), indicating complete absence of iron stores 1, 2
• Ferritin <30 μg/L: Generally indicates low body iron stores in patients without inflammation 2, 3
• Ferritin <45 μg/L: Optimal clinical cutoff providing good specificity (0.92), especially when inflammatory processes are suspected 1, 2
• Ferritin <100 μg/L: May still indicate iron deficiency in the presence of inflammatory conditions 4
• Ferritin >150 μg/L: Makes absolute iron deficiency unlikely, even with inflammation 1, 2

Critical caveat: Ferritin is an acute phase reactant and rises with inflammation, infection, liver disease, and malignancy. 1 In patients with chronic inflammatory conditions (heart failure, chronic kidney disease, inflammatory bowel disease), standard ferritin cutoffs become unreliable and higher thresholds must be used. 1, 2

Transferrin Saturation: Supporting Evidence

Transferrin saturation <20% supports the diagnosis of iron deficiency when ferritin is equivocal. 4, 3 This is calculated as: (serum iron/total iron binding capacity) × 100. 3

In patients without inflammation, a ferritin level of 46-99 ng/mL plus transferrin saturation <20% is diagnostic of iron deficiency. 5

Red Blood Cell Indices

Mean corpuscular hemoglobin (MCH) is more reliable than mean corpuscular volume (MCV) for diagnosing iron deficiency, as it is less dependent on storage conditions and equipment, and is reduced in both absolute and functional iron deficiency. 2

Typical findings include: 4

• Microcytosis: MCV <80 fL
• Hypochromia: Reduced MCH
• Elevated red cell distribution width (RDW), particularly in combined deficiencies

Additional Laboratory Markers

When standard tests are equivocal or inflammation is present: 1, 2

• Total iron binding capacity (TIBC): Raised in iron deficiency (>370 μg/dL)
• Soluble transferrin receptor (sTfR): Good marker in healthy subjects, but elevated with increased erythropoietic drive (hemolytic anemias, thalassemias)
• [sTfR/log₁₀ ferritin] ratio: May provide superior discrimination, particularly in chronic disease
• Red cell zinc protoporphyrin: Raised in iron deficiency
• Reticulocyte hemoglobin content: Provides early indication of functional iron deficiency

Therapeutic Trial as Diagnostic Tool

A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even when iron study results are equivocal. 2, 4 This represents a practical diagnostic approach when laboratory findings are borderline or confounded by inflammation.

Clinical Context: Who to Test

Testing for iron deficiency is indicated for: 3

• Patients with anemia of any degree
• Symptoms of iron deficiency (fatigue, pica, restless legs syndrome, dyspnea, exercise intolerance)
• Risk factors: heavy menstrual bleeding, pregnancy, inflammatory bowel disease, chronic kidney disease, heart failure, gastrointestinal bleeding, use of NSAIDs, post-bariatric surgery

In premenopausal women with non-anemic iron deficiency (low ferritin but normal hemoglobin), gastrointestinal investigation is generally not warranted unless there are GI symptoms or family history of GI pathology, as menstrual blood loss is the likely cause. 1 However, the threshold for investigation should be low in men, postmenopausal women, and those with GI symptoms. 1

Mandatory Screening Tests at Presentation

Once IDA is confirmed, initial investigation should include: 1, 4

• Urinalysis or urine microscopy to exclude renal tract blood loss
• Coeliac disease screening (tissue transglutaminase antibody), as it is found in 3-5% of IDA cases
• Bidirectional endoscopy (gastroscopy and colonoscopy) in men and postmenopausal women, as gastrointestinal blood loss is the most common cause in these populations