What lab findings are associated with iron deficiency?

Laboratory Findings in Iron Deficiency

Iron deficiency is diagnosed through a combination of complete blood count showing microcytic hypochromic anemia (late finding) and serum ferritin <15-30 μg/L (most specific early marker), with transferrin saturation <20% providing confirmatory evidence when ferritin is equivocal. 1, 2

Initial Screening Tests

Complete Blood Count (CBC) should be the first test ordered, as it provides multiple parameters that evolve as iron deficiency progresses 2:

• Hemoglobin and hematocrit are reduced only in late-stage iron deficiency when anemia has developed, making them insensitive for early detection 1, 2
• Mean Cell Hemoglobin (MCH) shows hypochromia and is more reliable than MCV because it is less dependent on storage conditions and the specific analyzer used 1
• Mean Cell Volume (MCV) demonstrates microcytosis, though this is a late finding that loses sensitivity in the presence of chronic disease, thalassemia, or B12/folate deficiency 1
• Red Cell Distribution Width (RDW) >14.0% combined with microcytosis strongly suggests iron deficiency anemia 2

Serum Iron Studies (Most Diagnostic)

Serum ferritin is the single most specific test for iron deficiency and should be measured in all suspected cases 1, 2:

• Ferritin <15 μg/L indicates absent iron stores with 99% specificity in the absence of inflammation 1, 2
• Ferritin <30 μg/L generally indicates low body iron stores 1
• Ferritin <45 μg/L provides optimal balance between sensitivity (captures more cases) and specificity (92%) for practical diagnosis 1
• Ferritin >150 μg/L essentially rules out absolute iron deficiency, even with concurrent inflammation 1

Transferrin saturation (TSAT) provides complementary information 2:

• TSAT <16-20% confirms iron deficiency, particularly when combined with low ferritin 2
• TSAT is calculated as (serum iron × 100)/total iron-binding capacity 2
• TSAT is less affected by inflammation than ferritin alone, making it valuable when inflammatory conditions coexist 2
• Among nonpregnant women, TSAT <16% has 93% specificity for iron deficiency 2

Total iron-binding capacity (TIBC) increases when iron stores are depleted, reflecting the body's attempt to capture more circulating iron 2

Serum iron is the least reliable marker due to significant diurnal variation (higher in morning, increases after meals) and substantial day-to-day fluctuation 2

Diagnostic Algorithm by Clinical Context

In otherwise healthy individuals without inflammation:

• Measure serum ferritin first 2
• If ferritin <15 μg/L: iron deficiency confirmed 1
• If ferritin 15-45 μg/L: add transferrin saturation; if TSAT <20%, iron deficiency likely 2
• If ferritin >45 μg/L: iron deficiency unlikely unless inflammation present 1

In patients with chronic inflammation, kidney disease, heart failure, or inflammatory bowel disease:

• Use ferritin <100 μg/L as the diagnostic threshold instead of <30 μg/L, because ferritin acts as an acute phase reactant and is falsely elevated 2
• Transferrin saturation becomes more important in these patients as it is less affected by inflammation 2
• Consider serum transferrin receptor (sTfR) if available, though most hospitals do not routinely offer this test 1

Advanced or Specialized Tests

• Erythrocyte protoporphyrin concentration detects early changes in iron status before anemia develops 2
• Serum transferrin receptor (sTfR) reflects cellular iron deficits and is less affected by inflammation, but is not widely available 1, 2
• Reticulocyte hemoglobin content provides information about recent iron availability for red blood cell production 1, 2
• Percent hypochromic red blood cells 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 diagnosis, as these only become abnormal after iron stores are completely depleted and erythropoiesis is impaired—missing the opportunity for early intervention 1, 2, 3

Do not ignore inflammatory markers when interpreting ferritin levels, as chronic disease, infection, hepatitis, cirrhosis, malignancy, or arthritis can raise ferritin independent of actual iron status 1, 2

Do not test iron parameters within 4 weeks of IV iron administration, as circulating iron interferes with assays and produces falsely elevated results 2

In men and postmenopausal women with confirmed iron deficiency, do not assume dietary insufficiency—approximately 62% have gastrointestinal bleeding from lesions (including malignancy) that require endoscopic investigation 2, 4

Do not assume microcytosis always means iron deficiency—obtain hemoglobin electrophoresis in patients with microcytosis and normal iron studies, particularly those of Mediterranean, African, or Southeast Asian descent, to exclude thalassemia 1

Timing of Reassessment

• 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 iron replacement is effective 2
• If hemoglobin does not increase appropriately, consider malabsorption of oral iron, continued bleeding, or an unidentified lesion 4