What labs should I order for a patient with hypoferritinemia (low iron count)?

Laboratory Evaluation for Low Iron Count (Hypoferritinemia)

For patients with hypoferritinemia, a comprehensive laboratory panel should include serum ferritin, transferrin saturation, complete blood count with indices, and screening for celiac disease to accurately diagnose iron deficiency and identify underlying causes. 1

Initial Laboratory Assessment

Core Iron Studies

• Serum ferritin: The most specific test for iron deficiency

  • <15 μg/L: Highly specific for iron deficiency (specificity 0.99)
  • <30 μg/L: Generally indicative of low body iron stores
  • <45 μg/L: Provides optimal trade-off between sensitivity and specificity 1

• Transferrin saturation: Reflects immediately available iron for hemoglobin synthesis

  • <16% suggests iron deficiency 1

• Serum iron and total iron-binding capacity (TIBC):

  • Low serum iron and raised TIBC are markers of iron deficiency 1, 2

Complete Blood Count Parameters

• Hemoglobin and hematocrit: To determine presence of anemia
• Mean cell hemoglobin (MCH): More reliable marker of iron deficiency than MCV
• Mean cell volume (MCV): To detect microcytosis
• Red blood cell count: Values below 4.04 × 10¹²/L may indicate iron deficiency anemia 3
• Percentage of hypochromic red cells: Normally <2.5% 1

Additional Testing Based on Clinical Context

For Suspected Inflammatory Conditions

• C-reactive protein (CRP): To exclude acute phase reactions that may falsely elevate ferritin 1, 4
• Erythrocyte sedimentation rate (ESR): Additional marker of inflammation 5

For Suspected Gastrointestinal Causes

• Celiac disease screening: Found in 3-5% of cases of iron deficiency anemia 1
• Stool guaiac test: To detect occult gastrointestinal bleeding 1

For Suspected Hemoglobinopathies

• Hemoglobin electrophoresis: Recommended in those with microcytosis and normal iron studies, particularly with appropriate ethnic background 1

Advanced Testing (When Available)

• Reticulocyte hemoglobin (Ret-He): Good predictor of bone marrow iron stores with a cut-off value of 22.4 pg (sensitivity 98.88%, specificity 84.21%) 6
• Serum transferrin receptor (sTfR): Good marker of iron deficiency in otherwise healthy subjects 1
• sTfR/log10 ferritin ratio: Superior discrimination, particularly in chronic disease 1

Interpretation of Results

Iron Deficiency Without Anemia

• Normal hemoglobin with low ferritin (<30 μg/L in adults >15 years)
• May present with fatigue despite normal hemoglobin 4

Iron Deficiency Anemia

• Low hemoglobin (<110 g/L in men, <100 g/L in non-menstruating women)
• Low ferritin (<30 μg/L)
• Microcytosis and hypochromia typically present 1

Important Considerations

1. False normal ferritin: In inflammatory conditions, ferritin (an acute phase protein) may appear normal despite iron deficiency 1

2. CBC alone is insufficient: Studies show individuals may have normal CBC parameters but reduced serum iron and ferritin, making them susceptible to developing iron deficiency anemia 7

3. Risk assessment: Age, sex, hemoglobin concentration, and mean cell volume are all independent predictors of risk of GI cancer in iron deficiency anemia 1

4. Special populations: In chronic kidney disease, additional markers may be needed as ferritin may not accurately reflect iron stores 5

By following this comprehensive laboratory evaluation, you can accurately diagnose iron deficiency, determine its severity, and guide appropriate treatment decisions to improve patient outcomes.