How do you interpret iron labs in an adult patient with a history of anemia?

Interpreting Iron Labs in Anemia

Serum ferritin is the single most useful test for diagnosing iron deficiency, with a threshold of <45 ng/mL providing optimal sensitivity and specificity in most clinical contexts. 1

Defining Anemia

Start by confirming anemia is present:

• Men: Hemoglobin <13 g/dL 1, 2
• Non-pregnant women: Hemoglobin <12 g/dL 1
• Pregnant women (2nd/3rd trimester): Hemoglobin <11 g/dL 1

Use your laboratory's lower limit of normal if it aligns with these WHO-defined thresholds. 1

Primary Iron Studies Interpretation

Ferritin Thresholds

Without inflammation present:

• <15 ng/mL: Highly specific for absent iron stores (specificity 99%) 1
• <30 ng/mL: Generally indicates low body iron stores 1
• <45 ng/mL: Optimal cutoff for iron deficiency (specificity 92%) 1
• >150 ng/mL: Unlikely to represent absolute iron deficiency, even with inflammation 1

With inflammation or chronic disease:

• <100 ng/mL: Diagnostic of iron deficiency 3
• <45 ng/mL: Still warrants investigation for iron deficiency, especially with concurrent anemia 1

Critical caveat: Ferritin is an acute phase reactant and rises with inflammation, chronic kidney disease, liver disease, malignancy, and infection. A "normal" ferritin may mask true iron deficiency in these conditions. 1

Transferrin Saturation (TSAT)

• <20%: Supports iron deficiency diagnosis 4, 3
• Calculated as: (serum iron ÷ total iron binding capacity) × 100 4
• Particularly useful when ferritin is equivocal (46-99 ng/mL in non-inflammatory states) 3
• In patients without inflammation: ferritin 46-99 ng/mL plus TSAT <20% confirms iron deficiency 3

Red Blood Cell Indices

• Mean Cell Hemoglobin (MCH): More reliable than MCV for detecting iron deficiency; less affected by storage conditions and machine variability 1
• Mean Cell Volume (MCV): Reduced in iron deficiency (microcytosis), but loses sensitivity with chronic disease, thalassemia, or B12/folate deficiency 1
• Both MCH and MCV: Can be normal in early iron deficiency or when coexisting conditions are present 1

Algorithmic Approach to Interpretation

Step 1: Confirm Iron Deficiency

Use ferritin as your primary test, adjusting thresholds based on inflammatory status as outlined above. 1

Step 2: When Iron Studies Are Equivocal

If ferritin is borderline (30-100 ng/mL) or you suspect false-normal ferritin due to inflammation:

• Check transferrin saturation (<20% supports iron deficiency) 1, 3
• Consider a therapeutic trial: Hemoglobin rise ≥10 g/L within 2 weeks of iron therapy strongly suggests absolute iron deficiency, even with equivocal labs 1

Step 3: Rule Out Alternative Causes of Microcytosis

If MCV is low but iron studies are normal:

• Consider thalassemia (MCV disproportionately low relative to anemia degree) 1
• Order hemoglobin electrophoresis, especially in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 1
• Consider anemia of chronic disease, sideroblastic anemia, or hemoglobinopathies 1

Step 4: Identify the Underlying Cause

Once iron deficiency is confirmed, investigate the source:

• Premenopausal women: Heavy menstrual bleeding is the most common cause 4, 5
• Men and postmenopausal women: Gastrointestinal blood loss until proven otherwise—warrants bidirectional endoscopy 1, 2, 3
• All patients: Test for celiac disease (tissue transglutaminase IgA with total IgA) and H. pylori (stool antigen or urea breath test) before endoscopy 1, 2

Common Pitfalls to Avoid

Pitfall 1: Relying on Hemoglobin/Hematocrit Alone

Normal hemoglobin and hematocrit do not exclude iron deficiency—these only decrease with severe depletion. 6 Always check ferritin and/or TSAT to detect early iron deficiency. 6

Pitfall 2: Missing Iron Deficiency in Inflammatory States

Ferritin can be falsely elevated in chronic kidney disease, heart failure, inflammatory bowel disease, cancer, and infections. 1, 4 In these patients, use lower ferritin thresholds (<100 ng/mL) or add TSAT to your interpretation. 1, 3

Pitfall 3: Over-Interpreting MCV

Microcytosis is not always present in iron deficiency, especially early on or when coexisting B12/folate deficiency or chronic disease exists. 1 MCH is more sensitive and reliable. 1

Pitfall 4: Ignoring Non-Anemic Iron Deficiency

Patients can have depleted iron stores (low ferritin) without anemia. 1 While GI investigation is generally not warranted in premenopausal women with non-anemic iron deficiency, it should be considered in men and postmenopausal women. 1

Special Populations

Chronic Kidney Disease

Functional iron deficiency is common. 1 Ferritin and TSAT interpretation requires adjustment per renal-specific guidelines, as standard thresholds may not apply. 1

Elderly Patients

Iron deficiency is often multifactorial (poor diet, reduced absorption, medications, chronic disease). 1 Ferritin interpretation is complicated by coexisting inflammatory conditions. 1 Consider transferrin saturation and therapeutic trial when ferritin is equivocal. 1

Pregnancy

Up to 84% of pregnant women in the third trimester have iron deficiency. 4 Use hemoglobin <11 g/dL as the anemia threshold in the second and third trimesters. 1

Additional Laboratory Tests (Less Commonly Used)

• Soluble transferrin receptor (sTfR): Good marker in healthy subjects, but elevated in hemolytic anemias and thalassemias 1
• sTfR/log ferritin ratio: May improve discrimination in chronic disease, but not widely available 1
• Reticulocyte hemoglobin, zinc protoporphyrin, % hypochromic red cells: Useful in specialized settings but not routinely performed 1