How do you differentiate anemia based on lab values, specifically complete blood count (CBC) and other relevant tests such as serum iron, ferritin, vitamin B12, and folate levels?

Differentiating Anemia Based on Laboratory Values

The most effective approach to differentiating anemia is through systematic laboratory analysis starting with complete blood count (CBC), reticulocyte count, and iron studies, followed by specific tests based on initial findings to determine the underlying cause and guide appropriate treatment.

Initial Laboratory Assessment

• Complete Blood Count (CBC) should be the first test performed for all patients with suspected anemia, including hemoglobin levels which define anemia as <12 g/dL for women and <13 g/dL for men 1
• Red Blood Cell Indices particularly Mean Corpuscular Volume (MCV) and Red Cell Distribution Width (RDW) are essential for initial classification of anemia 1
• Reticulocyte Count helps distinguish between production defects and increased destruction/loss of red blood cells 1

Classification Based on MCV and Reticulocyte Count

Microcytic Anemia (Low MCV)

• Iron Deficiency Anemia (IDA):

  • Low serum ferritin (<30 μg/L in non-inflammatory states) 1
  • Low transferrin saturation 1
  • Elevated RDW 1
  • In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency 1

• Thalassemia:

  • Normal or elevated ferritin 1
  • Requires hemoglobin electrophoresis for confirmation 1

Normocytic Anemia (Normal MCV)

• Anemia of Chronic Disease (ACD):

  • Elevated serum ferritin (>100 μg/L) 1
  • Low transferrin saturation (<20%) 1
  • Normal or low MCV and MCH 1
  • Elevated inflammatory markers (CRP) 1

• Mixed Deficiency Anemia:

  • Ferritin between 30-100 μg/L with inflammation 1
  • May have normal MCV due to counterbalancing effects of different deficiencies 1, 2
  • High RDW indicates coexisting deficiencies 1

Macrocytic Anemia (High MCV)

• Vitamin B12 Deficiency:

  • Low serum vitamin B12 levels 1
  • Elevated methylmalonic acid and homocysteine 1
  • May present with neurological symptoms 3

• Folate Deficiency:

  • Low serum folate or red cell folate 1
  • Elevated homocysteine 1

• Medication-Induced:

  • History of medications like azathioprine, methotrexate 1
  • May occur with alcohol abuse or hypothyroidism 1

Advanced Diagnostic Approach

Reticulocyte Response Analysis

• Low/Normal Reticulocytes: Indicates production defect (deficiencies, bone marrow failure) 1
• Elevated Reticulocytes: Suggests hemolysis or blood loss 1
  • Further investigate with haptoglobin, LDH, and bilirubin 1

Iron Studies Interpretation

• Serum Ferritin: Most sensitive marker for iron stores 1

  • <30 μg/L: Iron deficiency without inflammation 1
  • 30-100 μg/L with inflammation: Possible iron deficiency 1

  • 100 μg/L with low transferrin saturation: Anemia of chronic disease 1

• Transferrin Saturation: Represents iron available for erythropoiesis 1

  • <20% indicates functional or absolute iron deficiency 1

Special Considerations

• Mixed Anemia: When multiple deficiencies coexist, MCV may be normal despite underlying abnormalities 2

  • CHr (reticulocyte hemoglobin content) and CHCMr (reticulocyte hemoglobin concentration) can help differentiate mixed anemias 2

• Inflammatory Conditions: Alter interpretation of iron studies 1

  • CRP should be measured to assess inflammation 1
  • Soluble transferrin receptor levels may help distinguish IDA from ACD 1

Common Pitfalls to Avoid

• Relying solely on MCV for classification—coexisting conditions may neutralize MCV changes 1
• Misinterpreting ferritin without considering inflammatory status 1
• Overlooking mixed deficiency states which require comprehensive testing 2
• Failing to consider hemolysis when reticulocyte count is elevated 1
• Not investigating underlying causes of deficiencies (e.g., GI bleeding in iron deficiency) 1

When to Consult Hematology

• When cause of anemia remains unclear after extensive workup 1
• In cases of suspected bone marrow failure or malignancy 3
• With abnormalities in multiple cell lines (white cells, platelets) 1
• For refractory anemias not responding to appropriate supplementation 3