What are the initial lab studies for a patient with suspected iron deficiency anemia?

Initial Laboratory Studies for Iron Deficiency Workup

Begin with a complete blood count (CBC) and serum ferritin level—these two tests form the essential foundation for diagnosing iron deficiency anemia. 1, 2

Core Laboratory Tests

Hemoglobin and Ferritin (Required)

• Measure hemoglobin to confirm anemia: <13 g/dL in men, <12 g/dL in non-pregnant women, or <11 g/dL in pregnant women 2
• Measure serum ferritin to confirm iron deficiency: Use a cut-off of <45 ng/mL, which provides optimal sensitivity and specificity 1, 2
• This ferritin threshold is superior to the older 15 ng/mL cut-off and should be used preferentially 1

Complete Blood Count Parameters

• Obtain mean corpuscular volume (MCV): Microcytic anemia (MCV <80 fL) typically indicates iron deficiency 1
• Review red blood cell distribution width (RDW): Elevated RDW suggests iron deficiency 1
• Examine mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC): Low values support iron deficiency diagnosis 1, 3

Additional Tests in Specific Contexts

When Inflammation or Chronic Disease is Present

• Measure transferrin saturation if ferritin is 30-100 μg/L: This range suggests possible combined iron deficiency and anemia of chronic disease 1
• In patients with clinical or biochemical inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 1
• Calculate transferrin saturation (<20%) in patients with chronic kidney disease or inflammatory conditions: Ferritin acts as an acute-phase reactant and can be falsely elevated despite true iron deficiency 1, 2

Distinguishing Iron Deficiency from Anemia of Chronic Disease

• When ferritin is >100 μg/L AND transferrin saturation is <20%, this indicates anemia of chronic disease rather than iron deficiency 1
• Ferritin between 30-100 μg/L suggests a mixed picture of both conditions 1

Critical Pitfalls to Avoid

Do not order serum iron or total iron-binding capacity (TIBC) as initial tests—these have poor predictive value and high day-to-day variation compared to ferritin 1. The serum ferritin is the most specific indicator of depleted iron stores 1.

Do not perform fecal occult blood testing—it provides no benefit in the investigation of iron deficiency anemia 2.

Remember that ferritin is an acute-phase reactant: In patients with infection, inflammation, hepatitis, cirrhosis, or malignancy, ferritin may be elevated independent of iron status, masking true iron deficiency 1, 4. In these cases, use the higher ferritin threshold of 100 μg/L or add transferrin saturation to your assessment 1, 2.

Algorithmic Approach

1. Order CBC with hemoglobin and serum ferritin simultaneously 2
2. If hemoglobin is low AND ferritin <45 ng/mL: Diagnose iron deficiency anemia and proceed with evaluation for underlying cause 1, 2
3. If ferritin is 30-100 μg/L with evidence of inflammation: Add transferrin saturation to distinguish pure iron deficiency from mixed picture 1
4. If ferritin >100 μg/L with transferrin saturation <20%: Diagnose anemia of chronic disease 1
5. Review MCV from CBC: MCV <75-80 fL strongly supports iron deficiency (83% predictive value), while MCV >86 fL makes iron deficiency unlikely 3, 5