What are the key findings and tests for diagnosing microcytic hypochromic anemia on a peripheral smear?

Key Findings and Tests for Diagnosing Microcytic Hypochromic Anemia on Peripheral Smear

The diagnosis of microcytic hypochromic anemia requires evaluation of red blood cell indices, peripheral smear characteristics, and specific laboratory parameters including serum ferritin, iron studies, and in some cases, additional specialized tests to differentiate between the various causes. 1

Peripheral Smear Findings

• Key microscopic features:
  • Small red blood cells (microcytosis) - MCV < 83 μm³ 2
  • Reduced hemoglobin content (hypochromia) - increased central pallor
  • Possible anisocytosis (variation in cell size) - reflected by elevated RDW > 14% in iron deficiency 1
  • Possible poikilocytosis (variation in cell shape)

Essential Laboratory Parameters

The American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) recommend the following laboratory parameters to diagnose and classify microcytic hypochromic anemia 1:

Parameter	Iron Deficiency	Thalassemia Trait	Anemia of Chronic Disease
MCV	Low	Very low (<70 fl)	Low/Normal
RDW	High (>14%)	Normal (≤14%)	Normal/Slightly elevated
Ferritin	Low (<30 μg/L)	Normal	Normal/High
TSAT	Low	Normal	Low
RBC count	Normal/Low	Normal/High	Normal/Low

Diagnostic Algorithm

1. Initial assessment: Complete Blood Count (CBC) with red cell indices

   • Hemoglobin level (primary test for diagnosing anemia)
   • MCV < 83 μm³ indicates microcytosis 2
   • MCH < 27 pg indicates hypochromia 3

2. First-line testing: Serum ferritin

   • If low (<30 μg/L): Suggests iron deficiency anemia 1
   • If normal/elevated: Proceed to additional testing 4

3. Second-line testing:

   • Serum iron and total iron-binding capacity (TIBC)
   • Transferrin saturation (TSAT)
   • Free erythrocyte protoporphyrin (FEP) 4

4. Differential diagnostic tests:

   • Soluble transferrin receptor (sTfR) - elevated in iron deficiency, normal in thalassemia 3
   • sTfR/ferritin ratio - significantly higher in iron deficiency compared to other causes 3
   • Hemoglobin electrophoresis - for suspected thalassemia
   • Lead levels - if lead toxicity is suspected 4

Distinguishing Features Between Common Causes

Iron Deficiency Anemia

• Percentage of hypochromic cells > percentage of microcytic cells 5
• High RDW (>14%) 1
• Low ferritin (<30 μg/L) 1
• Low serum iron and high TIBC 4

Thalassemia Trait

• Percentage of microcytic cells > percentage of hypochromic cells 5
• Normal RDW (≤14%) 1
• Normal ferritin 1
• Normal or elevated RBC count 1
• Very low MCV (<70 fl) 1

Anemia of Chronic Disease

• Low/normal MCV 1
• Normal/slightly elevated RDW 1
• Normal/high ferritin 1
• Low TSAT 1

Important Pitfalls to Avoid

• Overlooking mixed deficiencies: Iron deficiency can coexist with other conditions like thalassemia or anemia of chronic disease 6
• Relying solely on ferritin: In inflammatory conditions, ferritin may be falsely elevated despite iron deficiency 1
• Missing functional iron deficiency: Patients may have functional iron deficiency despite normal or elevated ferritin levels, especially with chronic inflammatory conditions 1
• Inadequate investigation: Accepting anemia without thorough investigation can miss serious underlying pathology 1

Advanced Diagnostic Approaches

• The microcytic-hypochromic ratio (percentage of microcytes divided by percentage of hypochromic cells) can be highly effective in differentiating iron deficiency from thalassemia:

  • Ratio <0.9 suggests iron deficiency
  • Ratio >0.9 suggests thalassemia trait 5

• Bone marrow examination remains the gold standard for diagnosing iron deficiency when other tests are inconclusive, showing absent iron stores 2