Etiology

Macrocytic (MCV >100)

• Megaloblastic anemia: folic acid or Vitamin B12 deficiency
• Liver disease (target cells)
• Alcoholism
• Reticulocytosis
• Hypothyroidism
• Myelodysplastic syndrome
• Antiretrovirals, eg, AZT

Microcytic (MCV < 80)

• Iron deficiency
• Thalassemia
• Anemia of chronic disease
• Sideroblastic anemia
• Lead poisoning

Normocytic (MCV 80-100)

• Low reticulocyte count
• Iron deficiency (especially early)
• Anemia of chronic disease
• Chronic renal disease (low erythropoietin)
• Hypothyroidism, adrenal insufficiency, or hypopituitarism
• Primary bone marrow disorder
  • Aplastic anemia
  • Malignancy, eg, multiple myeloma, leukemia, metastases
  • Myelofibrosis
  • Myelodysplastic syndrome
  • Infection, eg, parvovirus B19 (causes red cell hypoplasia or aplastic anemia)
• High reticulocyte count
• Blood loss
• Hemolysis
  • Coombs positive (immune): autoimmune, drugs, infection, lymphoproliferative disease, Rh or ABO incompatibility
  • Coombs negative: intrinsic red cell disease
    1. Abnormal hemoglobin: sickle cell disease, thalassemia, methemoglobinemia
    2. Membrane defect: hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria
    3. Enzyme defect: G6PD deficiency, pyruvate kinase deficiency
  • Coombs negative: extrinsic disease
    1. Microangiopathic hemolytic anemia, eg, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, prosthetic valve hemolysis
    2. Splenic sequestration
    3. Infection: malaria, Clostridium, Borrelia
    4. Burns