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Difficulty: MediumInterpreting Laboratory Results

A physician is reviewing laboratory results for several patients presenting with microcytic anemia (Mean Corpuscular Volume < 80 fL). Match the following serum iron and hematologic profiles to their most likely diagnostic etiology.

Reference ranges:
Serum iron: 60-170 µg/dL
Total iron-binding capacity (TIBC): 240-450 µg/dL
Ferritin: 15-200 ng/mL
Transferrin saturation: 20-50%
Red Cell Distribution Width (RDW): 11.5-14.5%

  • Serum iron: 35 µg/dL, TIBC: 480 µg/dL, Ferritin: 8 ng/mL, Transferrin saturation: 7%Iron deficiency anemia
  • Serum iron: 40 µg/dL, TIBC: 210 µg/dL, Ferritin: 350 ng/mL, Transferrin saturation: 19%Anemia of chronic inflammation
  • Serum iron: 185 µg/dL, TIBC: 280 µg/dL, Ferritin: 450 ng/mL, Transferrin saturation: 66%Sideroblastic anemia
  • Serum iron: 95 µg/dL, TIBC: 310 µg/dL, Ferritin: 110 ng/mL, Transferrin saturation: 30%, RDW: 12%Beta-thalassemia minor

Answer

Profile 1 matches Iron deficiency anemia; Profile 2 matches Anemia of chronic inflammation; Profile 3 matches Sideroblastic anemia; Profile 4 matches Beta-thalassemia minor.
Interpreting microcytic anemias requires analyzing the interplay between serum iron, TIBC, and ferritin. Iron deficiency is characterized by depleted stores (low ferritin) and compensatory increased transferrin (high TIBC). Anemia of chronic inflammation is driven by hepcidin, which sequesters iron in macrophages (high ferritin) and decreases transferrin synthesis (low TIBC). Sideroblastic anemia involves an inability to incorporate iron into protoporphyrin, leading to systemic iron accumulation (high serum iron, high ferritin). Beta-thalassemia is a primary globin defect; therefore, iron studies remain normal, and patients typically present with uniform microcytosis (normal RDW).

Step-by-Step Solution

1
Evaluate ferritin levels as the primary indicator of total body iron stores.
A distinctly low ferritin uniquely identifies iron deficiency, while high or normal levels point to chronic disease, sideroblastic anemia, or thalassemia.
Ferritin is the most specific initial test to differentiate true systemic iron deficiency from other causes of microcytic anemia.
2
Assess TIBC and transferrin saturation in patients presenting with normal or high ferritin levels.
A low TIBC with high ferritin indicates anemia of chronic inflammation. Conversely, high transferrin saturation with high ferritin points to sideroblastic anemia or iron overload.
Hepcidin upregulation in chronic inflammation decreases transferrin (TIBC), whereas defective heme synthesis in sideroblastic anemia leaves excess iron unbound in serum.
3
Review the red cell distribution width (RDW) in the context of entirely normal iron studies.
Normal iron studies accompanied by a normal RDW in the setting of isolated microcytosis is indicative of thalassemia trait.
Thalassemia is a primary globin chain synthesis defect, meaning iron metabolism remains unaffected, and red cell sizing is uniformly microcytic without the size variation seen in early iron deficiency.

Key Concept

Differential diagnosis of microcytic anemia using serum iron studies.
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Interpreting Laboratory Results

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