How does iron deficiency anemia present on laboratory tests?

Laboratory Presentation of Iron Deficiency Anemia

Iron deficiency anemia presents on laboratory tests with low hemoglobin/hematocrit, low serum ferritin (<30 μg/L), low transferrin saturation (<20%), elevated total iron-binding capacity, and typically microcytic hypochromic red blood cells, though normal MCV can occur in early stages. 1, 2

Initial Screening Tests

Complete blood count (CBC) is the essential first step, measuring hemoglobin, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). 2, 3

Hemoglobin and Hematocrit

• Hemoglobin <13 g/dL in men or <12 g/dL in non-pregnant women defines anemia (WHO criteria: <130 g/L men, <120 g/L non-pregnant women). 1, 2
• Hemoglobin is preferred over hematocrit because it is more reproducible across laboratories and unaffected by storage time or patient variables like serum glucose. 2
• These are late indicators—they decrease only after iron stores are depleted and erythropoiesis is impaired, making them unreliable for detecting early iron deficiency. 1, 3, 4

Red Cell Indices

• MCV (mean corpuscular volume): Typically decreased (<80 fL) showing microcytosis, but normal MCV does not exclude iron deficiency as it is a late finding. 1, 2
• MCH (mean corpuscular hemoglobin): Reduced, indicating hypochromia; MCH may be more sensitive than MCV for iron deficiency as it detects both absolute and functional iron deficiency. 1
• RDW (red cell distribution width): Elevated (>14.0%) with microcytosis strongly suggests iron deficiency anemia. 2

Iron Studies: The Definitive Tests

Serum ferritin is the single most sensitive and specific test for iron stores and must be ordered to confirm iron deficiency. 1, 2

Serum Ferritin Interpretation

• <15 μg/L: 99% specificity for iron deficiency—diagnostic of depleted iron stores. 1, 2
• <30 μg/L: Generally indicates low body iron stores and confirms iron deficiency in the absence of inflammation. 1, 2, 3
• <45 μg/L: Provides 92% specificity and warrants investigation, especially in chronic inflammatory conditions. 2, 5
• <100 μg/L: Use this threshold when inflammation or chronic disease is present (chronic kidney disease, heart failure, inflammatory bowel disease, infection, hepatitis, cirrhosis, neoplasia, arthritis), as ferritin is an acute-phase reactant and can be falsely elevated. 1, 2, 5

Transferrin Saturation (TSAT)

• TSAT <20% confirms iron deficiency and reflects iron immediately available for hemoglobin synthesis. 2, 3, 5
• Calculated as: (serum iron × 100) / total iron-binding capacity (TIBC). 2, 5
• TSAT is less affected by inflammation than ferritin alone, making it valuable when inflammatory conditions are present. 1, 2
• Among nonpregnant women, TSAT <16% has 93% specificity for iron deficiency. 2

Serum Iron and TIBC

• Serum iron: Decreased in iron deficiency, but has significant diurnal variation and increases after meals, making it unreliable as a standalone test. 2, 5
• TIBC (total iron-binding capacity): Elevated in iron deficiency as the body attempts to maximize iron binding capacity. 2, 5

Diagnostic Algorithm

Order CBC with serum ferritin and transferrin saturation as the initial iron panel. 2, 3

1. If ferritin <15 μg/L (or <30 μg/L): Iron deficiency is confirmed. 2
2. If ferritin 15-45 μg/L: Add serum iron and TIBC to calculate TSAT; if TSAT <20%, iron deficiency is confirmed. 2
3. If inflammation is present: Use ferritin <100 μg/L as the diagnostic threshold. 1, 2
4. Good response to iron therapy (hemoglobin rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even if iron studies are equivocal. 1

Advanced or Specialized Tests

When standard iron studies are inconclusive, additional tests may be considered:

• Erythrocyte protoporphyrin concentration: Detects early changes in iron status. 1, 2
• Soluble transferrin receptor (sTfR): Reflects cellular iron deficits and is less affected by inflammation, though not routinely available in most hospitals. 1, 2
• Reticulocyte hemoglobin content (CHr or RET-He): Provides direct assessment of functional iron availability for erythropoiesis. 1, 2
• Percent hypochromic red blood cells (PHRBC): Can identify functional iron deficiency but requires specialized equipment and is time-sensitive. 2

Critical Pitfalls to Avoid

• Do not rely solely on hemoglobin and hematocrit for diagnosing iron deficiency—they are late indicators that only become abnormal after iron stores are depleted. 1, 2, 3, 4
• Do not ignore inflammatory markers when interpreting ferritin levels—chronic disease, infection, hepatitis, cirrhosis, neoplasia, or arthritis can raise ferritin independent of iron status, masking true iron deficiency. 1, 2, 5
• Do not assume normal MCV excludes iron deficiency—microcytosis is a late finding and normal MCV can occur in early iron deficiency. 1, 2
• Do not test iron parameters within 4 weeks of receiving IV iron—circulating iron interferes with assays and gives falsely elevated results. 2
• In men and postmenopausal women with iron deficiency anemia, do not assume dietary insufficiency—approximately 62% have gastrointestinal bleeding from lesions requiring further investigation. 2, 6
• Recognize that serum iron has substantial day-to-day variation, greater than hemoglobin or hematocrit, limiting its diagnostic utility when measured in isolation. 2

Monitoring Response to Treatment

• Recheck iron parameters 4-8 weeks after starting supplementation to assess response. 2
• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks if treatment is working. 2
• A hemoglobin rise ≥10 g/L within a 2-week timeframe is highly suggestive of iron deficiency. 1