Laboratory Tests for Microcytic Anemia with Low Hemoglobin, Hematocrit, MCV, and MCHC
For microcytic anemia with low hemoglobin, hematocrit, MCV, and MCHC, iron studies should be ordered first, including serum ferritin, transferrin saturation, serum iron, and total iron-binding capacity to confirm iron deficiency anemia. 1
Initial Laboratory Evaluation
Essential Iron Studies:
- Serum ferritin: Most specific test for iron deficiency; levels <15 μg/L indicate absent iron stores, <30 μg/L indicate low iron stores 1
- Transferrin saturation: Helps identify available iron for erythropoiesis; low values indicate iron deficiency 1
- Serum iron: Typically low in iron deficiency 1
- Total iron-binding capacity (TIBC): Usually elevated in iron deficiency 1
Additional Recommended Tests:
- Reticulocyte count: Assesses bone marrow response to anemia; low count suggests iron deficiency or impaired erythropoiesis 1
- Red cell distribution width (RDW): Typically elevated in iron deficiency anemia; helps distinguish from other causes of microcytic anemia 1, 2
- C-reactive protein (CRP): Important to identify inflammation that may affect ferritin interpretation 1
Differential Diagnosis Considerations
The pattern of low hemoglobin, hematocrit, MCV, and MCHC strongly suggests iron deficiency anemia, but other conditions must be ruled out:
For Thalassemia:
- Hemoglobin electrophoresis: Essential if thalassemia is suspected, especially with microcytosis disproportionate to anemia severity or normal iron studies 1
- Family history: Important for hereditary anemias 2
For Anemia of Chronic Disease:
- Ferritin may be normal or elevated (>100 μg/L) despite functional iron deficiency 1
- Transferrin saturation is typically low 1, 2
For Combined Deficiencies:
- Vitamin B12 and folate levels: To rule out concurrent deficiencies 1
Interpretation Guide
| Parameter | Iron Deficiency | Anemia of Chronic Disease | Thalassemia |
|---|---|---|---|
| MCV | Low (<80 fL) | Low or normal | Very low |
| MCH | Low | Low or normal | Very low |
| Serum Ferritin | Low (<15 μg/L) | Normal or high (>100 μg/L) | Normal |
| TSAT | Low | Low | Normal |
| RDW | Elevated | Normal or slightly elevated | Normal |
Important Clinical Considerations
- In the presence of inflammation, serum ferritin up to 100 μg/L may still be consistent with iron deficiency 1
- A therapeutic trial of iron can be both diagnostic and therapeutic - a hemoglobin rise ≥10 g/L within 2 weeks strongly suggests iron deficiency, even with equivocal iron studies 1
- For patients with inflammatory conditions, additional markers like percent hypochromic red cells or reticulocyte hemoglobin content may be helpful if available 1
Common Pitfalls to Avoid
- Relying solely on hemoglobin/hematocrit: These are late indicators of iron deficiency 1
- Misinterpreting ferritin in inflammation: Ferritin is an acute phase reactant and may be falsely normal or elevated in inflammatory states 1
- Overlooking combined deficiencies: Iron deficiency can coexist with B12/folate deficiency, potentially neutralizing MCV changes 1
- Inadequate follow-up: Persistent anemia despite iron therapy warrants further investigation for malabsorption or ongoing blood loss 3, 4
Following this systematic approach will help identify the cause of microcytic anemia and guide appropriate treatment to improve patient outcomes.