What is hypochromic anemia?

Hypochromic Anemia: Diagnosis and Management

Hypochromic anemia is characterized by red blood cells with reduced hemoglobin concentration (less than 28 g/dL per cell), appearing pale on microscopy, and is most commonly caused by iron deficiency, but can also result from chronic disease, thalassemia, or other conditions affecting hemoglobin synthesis. 1

Types and Causes of Hypochromic Anemia

Hypochromic anemia is typically microcytic (small red blood cells with MCV <80 fL) and has several potential causes:

1. Iron Deficiency Anemia (IDA)

   • Most common cause worldwide (~80% of all anemia cases) 2
   • Results from inadequate iron for hemoglobin synthesis
   • High-risk populations: infants, toddlers, premenopausal women, pregnant women, elderly

2. Anemia of Chronic Disease (ACD)

   • Caused by functional iron deficiency (iron trapped in storage)
   • Common in hospitalized patients and elderly
   • Associated with chronic inflammation, infection, or malignancy

3. Thalassemia

   • Genetic disorder affecting hemoglobin chain synthesis
   • Typically very low MCV with normal ferritin levels

4. Sideroblastic Anemia

   • Defective heme synthesis
   • May respond to vitamin B6 (pyridoxine) supplementation 1

5. Other Causes

   • Aluminum toxicity (particularly in dialysis patients) 3
   • Lead poisoning
   • Hemoglobin E disorders

Diagnostic Approach

Initial Testing

• Complete blood count (CBC) with differential
• Red cell indices (MCV, MCH, RDW)
• Peripheral blood smear examination
• Serum ferritin
• Transferrin saturation (TSAT)
• Serum iron and total iron-binding capacity (TIBC)
• C-reactive protein (CRP) to assess inflammation 4, 1

Laboratory Differentiation

Parameter	Iron Deficiency	Anemia of Chronic Disease	Thalassemia
MCV	Low (<80 fL)	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
Hypochromic RBCs	>2.5%	Variable	Present

Additional Testing Based on Clinical Suspicion

• Hemoglobin electrophoresis (for thalassemia)
• Free erythrocyte protoporphyrin (elevated in IDA, ACD, and lead toxicity)
• Reticulocyte count (low in IDA and ACD, normal in thalassemia)
• Bone marrow examination (gold standard for confirming iron deficiency) 5
• Percentage of hypochromic red cells (>2.5% indicates iron deficiency) 4, 6

Management Approach

Iron Deficiency Anemia

1. Oral Iron Supplementation

   • Ferrous sulfate 200 mg twice daily
   • Continue for 3 months after hemoglobin normalizes
   • Add ascorbic acid (250-500 mg twice daily) to enhance absorption 1

2. Intravenous Iron

   • For inadequate response to oral therapy (<1.0 g/dL increase after 14 days)
   • For patients with malabsorption or inflammatory bowel disease
   • For patients with chronic kidney disease 1

3. Investigate Underlying Cause

   • GI bleeding (stool guaiac test recommended) 4
   • Malabsorption
   • Increased requirements (pregnancy, growth)
   • Blood loss

Anemia of Chronic Disease

• Treat underlying inflammatory condition
• Consider erythropoiesis-stimulating agents (ESAs) for persistent anemia
• Intravenous iron may be beneficial despite normal or elevated ferritin 1, 2

Monitoring Response

• Repeat CBC in 2-4 weeks to assess response
• Target hemoglobin rise of ≥10 g/L within 2 weeks indicates good response
• Monitor ferritin and transferrin saturation
• Continue follow-up to prevent recurrence 1

Special Considerations

Chronic Kidney Disease

• Regular screening for anemia is required
• Hypochromic red cells >2.5% suggests iron deficiency
• Consider erythropoietin therapy for EPO deficiency
• Higher ferritin targets may be needed (>100 ng/mL) 4

Pregnancy

• Higher iron requirements (30 mg/day)
• Increase to 60-120 mg/day for anemia during pregnancy 1

Common Pitfalls to Avoid

1. Relying solely on MCV or MCH without confirming iron status
2. Misinterpreting ferritin levels in inflammatory states (ferritin is an acute phase reactant)
3. Failing to investigate underlying causes of iron deficiency
4. Overlooking concurrent deficiencies (B12, folate)
5. Excessive iron supplementation in conditions with elevated ferritin 1

Hypochromic anemia requires thorough investigation to determine the underlying cause, as treatment approaches differ significantly between iron deficiency anemia and other conditions like anemia of chronic disease or thalassemia.