What is hypochromic anemia?

Hypochromic Anemia: Definition, Causes, and Management

Hypochromic anemia refers to a condition characterized by red blood cells with reduced hemoglobin concentration, defined as individual cells containing less than 28 g/dL of hemoglobin, with normally less than 2.5% of red blood cells being hypochromic. 1

Definition and Identification

• Hypochromic red blood cells appear pale on microscopic examination due to their reduced hemoglobin content 1
• Hypochromia is typically identified by decreased Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) values on complete blood count 1, 2
• MCH is considered a more reliable marker of iron deficiency than Mean Corpuscular Volume (MCV) as it is less dependent on storage and counting machine variables 1
• Normally, less than 2.5% of red blood cells should be hypochromic 1

Common Causes of Hypochromic Anemia

• Iron deficiency anemia - the most common cause of hypochromic anemia worldwide 1, 3
• Thalassemia - genetic disorders affecting hemoglobin synthesis 1, 4
• Anemia of chronic disease/inflammation - particularly in chronic kidney disease 1
• Sideroblastic anemia - disorders of heme synthesis 1
• Genetic disorders of iron metabolism - including hypotransferrinemia, SLC11A2 defects, and STEAP3 defects 1

Diagnostic Approach

• Complete blood count with red cell indices (MCH, MCHC, MCV) is the initial test for suspected hypochromic anemia 1
• Iron studies should include serum ferritin, transferrin saturation (TSAT), serum iron, and total iron-binding capacity (TIBC) 1
• Serum ferritin <15 μg/L is highly specific for iron deficiency (specificity 0.99) 1
• In chronic inflammatory conditions, ferritin may be falsely normal or elevated despite iron deficiency 1
• Percentage of hypochromic red cells >10% suggests functional iron deficiency, particularly in patients on erythropoietin therapy 5
• Bone marrow assessment of iron stores remains the definitive test for distinguishing iron deficiency from other causes of hypochromic anemia 3, 6

Differential Diagnosis

• Iron Deficiency vs. Thalassemia: In iron deficiency, the percentage of hypochromic cells is typically higher than the percentage of microcytic cells, while in beta-thalassemia trait, the percentage of microcytes is higher than hypochromic cells 7, 4
• Iron Deficiency vs. Anemia of Chronic Disease: Serum ferritin, transferrin saturation, and response to iron therapy help differentiate 1
• Coexistence of Conditions: Multiple causes of hypochromic anemia may coexist in the same patient, particularly iron deficiency with thalassemia trait 4

Management Principles

• Treatment should target the underlying cause rather than just the anemia 1, 3

• For iron deficiency anemia:

  • Oral iron supplementation is first-line therapy (ferrous sulfate 200 mg three times daily or equivalent) 2
  • Monitor response with repeat CBC after 2-4 weeks of therapy 2
  • Continue iron therapy for 3 months total after correction to replenish stores 2
  • Investigate for source of blood loss, particularly gastrointestinal bleeding in non-menstruating patients 1

• For thalassemia:

  • Genetic counseling is recommended 1, 4
  • Avoid unnecessary iron supplementation unless concurrent iron deficiency is confirmed 1

• For chronic kidney disease-related hypochromic anemia:

  • Evaluate iron status before initiating erythropoietin therapy 1
  • Target higher iron parameters (ferritin, TSAT) to support erythropoiesis during erythropoietin therapy 1
  • Monitor percentage of hypochromic red cells as a sensitive marker of functional iron deficiency 5

Monitoring and Follow-up

• For iron deficiency treatment:

  • Monitor hemoglobin, MCH, and MCHC after 2-4 weeks of iron therapy 2
  • After correction, monitor CBC at 3-month intervals for one year 2
  • Investigate persistent or recurrent hypochromic anemia despite adequate treatment 1

• For chronic kidney disease patients:

  • Regular monitoring of iron parameters and percentage of hypochromic red cells is recommended 1, 5
  • Adjust iron supplementation based on response to therapy and iron parameters 1

Important Pitfalls to Avoid

• Don't assume all hypochromic anemia is due to iron deficiency without appropriate testing 3, 6
• Don't start iron therapy without establishing the cause of hypochromic anemia 6
• Don't overlook the possibility of gastrointestinal bleeding in non-menstruating patients with iron deficiency 1
• Don't rely solely on serum ferritin in patients with inflammatory conditions, as it may be falsely elevated 1
• Don't miss coexisting conditions, such as iron deficiency in patients with thalassemia trait 4