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

Diagnostic Criteria for Iron Deficiency Anemia in Adults

Iron deficiency anemia is diagnosed by demonstrating both anemia (hemoglobin below normal range) and iron deficiency (serum ferritin <45 ng/mL in patients without inflammation, or <100 ng/mL in those with inflammatory conditions), with transferrin saturation <20% providing additional confirmation when ferritin is equivocal. 1

Defining Anemia

Hemoglobin thresholds for anemia: 1, 2

• Men over 15 years: Hb <130 g/L
• Non-pregnant women over 15 years: Hb <120 g/L
• Pregnant women (2nd/3rd trimester): Hb <110 g/L

The WHO-defined thresholds should guide laboratory reference ranges, though local population variations exist. 1 Investigation should be considered at any level of anemia when iron deficiency is present, as higher hemoglobin cutoffs (such as <110 g/L in men or <100 g/L in non-menstruating women) will miss cases of serious pathology including colorectal cancer. 1

Confirming Iron Deficiency

Primary Diagnostic Test

Serum ferritin is the single most useful and specific marker for iron deficiency: 1, 2

• Ferritin <15 μg/L: Diagnostic of absent iron stores
• Ferritin <30 μg/L: Generally indicates low body iron stores
• Ferritin <45 ng/mL: Recommended diagnostic threshold by the American Gastroenterological Association for optimal sensitivity and specificity 1, 3

Critical caveat: Ferritin is an acute phase protein and can be falsely elevated in inflammatory conditions (infection, chronic disease, malignancy). 1 In patients with inflammation, ferritin <100 μg/L may still indicate iron deficiency. 2, 3

Supplementary Iron Studies

When ferritin is equivocal (46-99 ng/mL) or inflammation is suspected: 1

• Transferrin saturation <20%: Supports iron deficiency diagnosis 2, 3
• Low serum iron
• Elevated total iron-binding capacity
• Elevated serum transferrin receptor

Red Blood Cell Indices

Mean corpuscular hemoglobin (MCH) is more reliable than MCV as it is less dependent on storage conditions and counting machines, and remains reduced in both absolute and functional iron deficiency. 1 MCH may be more sensitive than MCV for detecting iron deficiency. 1

Mean corpuscular volume (MCV) typically shows microcytosis, though both MCH and MCV lose sensitivity in the presence of: 1

• Chronic disease
• Thalassemia (MCV reduced disproportionately to anemia level)
• Vitamin B12/folate deficiency

Important pitfall: In patients with microcytosis and normal iron studies, particularly those of appropriate ethnic background, hemoglobin electrophoresis is recommended to exclude thalassemia and prevent unnecessary gastrointestinal investigation. 1

Therapeutic Diagnostic Test

A hemoglobin rise ≥10 g/L within a 2-week timeframe after starting iron therapy is highly suggestive of absolute iron deficiency, even when iron study results are equivocal. 1, 2 This represents a strong recommendation with 100% consensus from the British Society of Gastroenterology. 1

Algorithmic Approach to Diagnosis

1. Measure hemoglobin to confirm anemia using population-specific thresholds 1

2. Check serum ferritin as the primary diagnostic test 1, 2

   • If <45 ng/mL without inflammation: Iron deficiency confirmed 1, 3
   • If 46-99 ng/mL: Add transferrin saturation 1, 3
     • If transferrin saturation <20%: Iron deficiency confirmed 2, 3
   • If ferritin <100 ng/mL with inflammation present: Iron deficiency likely 2, 3

3. Review red cell indices (MCH, MCV) for supporting evidence of iron deficiency 1, 2

4. If iron studies are equivocal: Consider therapeutic trial of iron with hemoglobin reassessment in 2 weeks 1

   • Rise ≥10 g/L confirms iron deficiency 1, 2

5. Once iron deficiency anemia is confirmed, investigate underlying cause with urinalysis, celiac disease screening, and bidirectional endoscopy in at-risk populations (men and postmenopausal women). 1, 2