What lab work is recommended to diagnose and manage iron deficiency?

Laboratory Workup for Iron Deficiency

The minimum initial laboratory workup for diagnosing iron deficiency should include a complete blood count (CBC), serum ferritin, transferrin saturation (TSAT), and C-reactive protein (CRP). 1, 2

Initial Screening Tests

Start with these core tests:

• Complete Blood Count (CBC) with red cell indices including hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) 1, 2
• Serum ferritin as the primary marker of iron stores 1, 2
• Transferrin saturation (TSAT) to assess iron immediately available for erythropoiesis 1, 2
• C-reactive protein (CRP) to detect inflammation that may affect ferritin interpretation 1

Why These Tests Matter

Hemoglobin is preferred over hematocrit because it is more reproducible across laboratories and not affected by storage time or patient variables like serum glucose. 2 However, hemoglobin and hematocrit are late indicators of iron deficiency—they only become abnormal after iron stores are depleted and erythropoiesis is impaired. 2

RDW is particularly useful: an elevated RDW (>14.0%) combined with microcytosis strongly suggests iron deficiency anemia. 2 A high RDW can also help identify situations where microcytosis and macrocytosis coexist and neutralize each other, resulting in a falsely normal MCV. 1

Diagnostic Thresholds

Without Inflammation Present

• Ferritin <30 ng/mL indicates iron deficiency 1, 2
• Ferritin <15 ng/mL has 99% specificity for iron deficiency 2
• Ferritin <45 ng/mL provides 92% specificity and is the recommended cutoff by the American Gastroenterological Association 1, 2
• TSAT <20% confirms iron deficiency 1, 2

With Inflammation or Chronic Disease

This is a critical distinction: Ferritin is an acute-phase reactant and can be falsely elevated in the presence of inflammation, infection, chronic disease, hepatitis, cirrhosis, neoplasia, or arthritis. 2, 3

• Ferritin <100 ng/mL should be used as the diagnostic threshold when inflammation is present 1, 2
• TSAT <20% remains a reliable indicator as it is less affected by inflammation than ferritin 2, 3

For patients with inflammatory bowel disease specifically, if ferritin is between 30-100 ng/mL, this suggests a combination of true iron deficiency and anemia of chronic disease. 1

Additional Tests for Unclear Cases

When the diagnosis remains uncertain after initial testing, add:

• Reticulocyte count to assess bone marrow response to anemia 1

  • Low or "normal" reticulocytes indicate inability to respond properly, suggesting deficiencies or bone marrow disease
  • Increased reticulocytes indicate increased red cell formation and exclude deficiencies; instead consider hemolysis 1

• Vitamin B12 and folic acid if macrocytosis is present or suspected 1

• Haptoglobin, lactate dehydrogenase, and bilirubin if hemolysis is suspected (elevated reticulocytes) 1

• Soluble transferrin receptor (sTfR) reflects cellular iron deficits and is less affected by inflammation, though not routinely available at most hospitals 2

• Reticulocyte hemoglobin content provides direct assessment of functional iron availability but requires specialized equipment 2

Monitoring Frequency

For Inflammatory Bowel Disease Patients

• Every 6-12 months for patients in remission or with mild disease 1
• Every 3 months for outpatients with active disease 1

After Starting Iron Supplementation

Do not check iron parameters within 4 weeks of receiving IV iron—circulating iron interferes with assays and gives falsely elevated results. 2

• Recheck iron parameters at 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

Common Pitfalls to Avoid

Do not rely solely on hemoglobin and hematocrit for diagnosis—these are late indicators that only become abnormal after iron stores are depleted. 2

Do not ignore inflammatory markers when interpreting ferritin levels. Chronic disease, infection, or inflammation can mask true iron deficiency by elevating ferritin independent of iron status. 2

Do not test iron parameters too soon after IV iron administration—wait at least 4 weeks to avoid spurious 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 These patients require bidirectional endoscopy. 1

Recognize that serum iron has significant diurnal variation and increases after meals, making it less reliable as a standalone test. 2

Underlying Cause Investigation

Once iron deficiency is confirmed, test for underlying causes:

• Non-invasive H. pylori testing (conditional recommendation for asymptomatic patients with iron deficiency anemia) 1
• Celiac disease serologic testing (tissue transglutaminase antibodies) before proceeding to small bowel biopsy 1, 2
  • Check for IgA deficiency if TTG is negative but clinical suspicion remains, as IgA deficiency causes falsely negative TTG readings 2
• Bidirectional endoscopy is strongly recommended for postmenopausal women and men with iron deficiency anemia 1