Etiology

• Defective heme synthesis

  • Iron deficiency anemia (IDA): the most common

  • Lead poisoning

  • Anemia of chronic disease (late phase)

  • Sideroblastic anemia

• Defective globin chain: Thalassemia

The causes of microcytic anemia can be remembered with IRON LAST: IRON deficiency, Lead poisoning, Anemia of chronic disease, Sideroblastic anemia, Thalassemia.

1. Hemolytic anemia

2. Nonhemolytic normocytic anemia

• Intrinsic defects

  • Hemoglobinopathies

    • Sickle cell anemia

    • HbC disease

  • Enzyme deficiencies

    • Pyruvate kinase deficiency

    • G6PD deficiency

  • Membrane defects

    • Paroxysmal nocturnal hemoglobinuria

    • Hereditary spherocytosis

• Extrinsic defects

  • Autoimmune hemolytic anemia

  • Microangiopathic hemolytic anemia

  • Macroangiopathic hemolytic anemia

  • Infections

  • Mechanical destruction

• Blood loss

• Aplastic anemia

• Anemia of chronic kidney disease

• Iron deficiency anemia (early phase)

• Anemia of chronic disease (early phase)

• Dilutional anemia of pregnancy

Although overall blood volume increases in pregnancy, plasma volume expands more than RBC mass, leading to dilutional anemia of pregnancy.

1. Megaloblastic anemia

2. Nonmegaloblastic anemia

• Vitamin B12 deficiency

• Folate deficiency

• Medications

  • Phenytoin

  • Sulfa drugs

  • Trimethoprim

  • Hydroxyurea

  • MTX

  • 6-mercaptopurine

• Fanconi anemia

• Orotic aciduria

• Vitamin B12 stores last up to 3–5 years.

• Folic acid stores last for only about 3 months.

• Impairs absorption of folic acid in the small intestine

Inhibits dihydrofolate reductase

Interferes with DNA synthesis

• Liver disease

• Alcohol use

• Diamond-Blackfan anemia

• Myelodysplastic syndrome

• Multiple myeloma

• Hypothyroidism

The liver plays an important role in lipid synthesis, which is required for cell membranes, including those of RBCs.

Alcohol use alone (i.e., independent of liver disease, folate deficiency, or vitamin B12 deficiency) can cause macrocytic anemia, although the pathophysiology is not completely understood. Alcohol use can also lead to folate and vitamin B12 deficiency, but these deficiencies will cause megaloblastic anemia.