What labs should be ordered for a patient suspected of having iron deficiency anemia?

Laboratory Testing for Iron Deficiency Anemia

Order hemoglobin/hematocrit AND serum ferritin as your initial diagnostic tests, with ferritin <45 ng/mL plus hemoglobin <13 g/dL in men or <12 g/dL in non-pregnant women confirming iron deficiency anemia. 1

Essential Initial Tests

Complete Blood Count (CBC)

• Hemoglobin thresholds for anemia: <13 g/dL in men, <12 g/dL in non-pregnant women, <11 g/dL in pregnant women 1
• Red cell indices provide supporting evidence:
  • Mean corpuscular volume (MCV): microcytosis suggests iron deficiency but loses sensitivity with concurrent chronic disease or thalassemia 1
  • Mean corpuscular hemoglobin (MCH): more reliable than MCV as it's less machine-dependent and detects both absolute and functional iron deficiency 1
  • Red cell distribution width (RDW): elevated in iron deficiency, helpful when microcytosis and macrocytosis coexist 1
• Reticulocyte count: low or normal indicates inappropriate erythropoiesis from deficiency; elevated suggests hemolysis 1

Serum Ferritin

• Most specific single test for iron deficiency 1
• Diagnostic cutoffs:
  • <15 µg/L indicates absent iron stores 1
  • <30 µg/L indicates low body iron stores 1, 2
  • <45 ng/mL is the optimal threshold when combined with anemia criteria 1
• Critical caveat: Ferritin is an acute phase reactant and can be falsely elevated with inflammation, chronic kidney disease, or infection 1

Additional Iron Studies

Transferrin Saturation (TSAT)

• Calculate as: (serum iron ÷ total iron binding capacity) × 100 2
• <20% indicates iron deficiency 2
• <30% may support diagnosis when ferritin is equivocal 1
• Particularly useful when ferritin may be falsely normal due to inflammation 1

Complete Iron Panel Components

When diagnosis remains unclear, order: 1

• Serum iron
• Total iron binding capacity (TIBC)
• Transferrin
• Transferrin saturation

Expanded Workup for Specific Scenarios

When Ferritin is Equivocal or Inflammation Suspected

• Serum transferrin receptor (sTfR): elevated in true iron deficiency, normal in anemia of chronic disease 1
• C-reactive protein (CRP): helps interpret ferritin in inflammatory states 1
• Percentage of hypochromic red cells: >2.5% suggests iron deficiency 1
• Reticulocyte hemoglobin content: early indicator of functional iron deficiency 1

When Microcytosis Present with Normal Iron Studies

• Hemoglobin electrophoresis: rule out thalassemia, particularly in appropriate ethnic backgrounds 1

When Macrocytosis Present

• Vitamin B12 and folate levels: exclude megaloblastic anemia 1

Additional Testing for Underlying Causes

• Celiac serology (tissue transglutaminase antibody): 2-5% of iron deficiency anemia patients have celiac disease 1
• Stool guaiac test: screen for gastrointestinal blood loss 1
• H. pylori testing: non-invasive testing recommended before endoscopy 1

Diagnostic Confirmation Strategy

If iron studies are equivocal, a therapeutic trial of oral iron can be both diagnostic and confirmatory: 1

• Hemoglobin rise ≥10 g/L within 2 weeks strongly suggests absolute iron deficiency 1
• This approach is particularly useful when ferritin interpretation is complicated by inflammation 1

Common Pitfalls to Avoid

• Do not rely on hemoglobin alone: isolated hemoglobin has low sensitivity and specificity for iron deficiency 3
• Do not assume dietary deficiency explains the anemia: borderline iron-deficient diets are common but full gastrointestinal evaluation is still required 1
• Do not stop investigation at ferritin >45 ng/mL if clinical suspicion is high: consider inflammatory conditions elevating ferritin and check transferrin saturation 1
• Do not skip celiac testing: even asymptomatic patients warrant screening given 2-5% prevalence 1

Monitoring After Treatment

• Target ferritin >100 ng/mL to confirm iron store restoration 1
• Continue hemoglobin monitoring after resolution of anemia 1