Hemolytic Anemia: Definition, Diagnosis, and Complications

Hemolytic Anemia

• Hemolytic anemia is a type of anemia that results from the shortened survival of RBCs.
• Normally, the life span of RBCs is 100-120 days, with about 1% of RBCs being removed from the circulation each day and replaced by an equal number of new cells from the bone marrow.

General Features of Hemolytic Anemia

• Anemia: the degree of anemia depends on the rate of hemolysis and the efficiency of bone marrow.
• Jaundice: unconjugated hyperbilirubinemia due to bilirubin overload, usually mild as the liver can increase its capacity to conjugate bilirubin several folds.
• Hepatosplenomegaly: occurs due to hemosiderosis and extramedullary hematopoiesis, with the liver and spleen being enlarged.
• Characteristic skeletal manifestations:
  • Expansion of the medullary spaces of the skull and hands.
  • Abnormal mongoloid facies.
  • Prominence of malar eminences.
  • Frontal bossing.
  • Depression of the nose and exposure of the upper central teeth.

Investigations of Chronic Hemolytic Anemia

• Indirect evidences of hemolysis:
  • Sustained reticulocytosis with low hemoglobin level.
  • Lowering or reversal of the myeloid/erythroid ratio in the bone marrow.
  • Blood chemistry:
    • Unconjugated hyperbilirubinemia.
    • Increased serum iron.
    • Diminished iron binding capacity.
    • Decreased plasma concentration of haptoglobin and hemopexin.
  • Stool: increased stercobilinogen.
  • Urine: increased urobilinogen.
  • Characteristic X-ray findings:
    • Hair-on-end appearance on skull radiograph due to widening of the diploic spaces.
    • Loss of the waist of the metacarpal bones (balloning) with rarefaction.
• Direct evidences of hemolysis:
  • Determination of RBCs life span by injection of radioactive chromium (51Cr) tagged RBCs into the circulation.
  • Identification of free hemoglobin in the plasma and urine (indicates intravascular hemolysis after saturation of the binding proteins).

Complications of Hemolytic Anemia

• Hemosiderosis and increased body iron:
  • Short life span of RBCs.
  • Frequent blood transfusion.
  • Increased intestinal iron absorption.
• Manifestations of hemosiderosis:
  • Myocardium: uncontrolled heart failure.
  • Liver: liver cirrhosis.
  • Endocrinal dysfunction:
    • Pancreatic dysfunction: diabetes mellitus.
    • Pituitary affection: growth retardation.
    • Gonadal dysfunction: delayed puberty.
    • Adrenal gland: adrenal failure.
    • Thyroid and parathyroid dysfunction.
• Gallstones:
  • Pigmented gallstones formed of calcium bilirubinate.
  • Develops usually after the age of 4 years.
• Anemic heart failure.
• Complications of blood transfusion: hepatitis, AIDS.
• Aplastic crisis:
  • Episodes of bone marrow failure manifest by severe anemia and reticulocytopenia.
  • Usually precipitated by viral infection.
• Hypersplenism:
  • An enlarged spleen with increasing demand for blood transfusion.
  • Depression of one or more of cellular elements of blood.
  • Active formation of that element in the bone marrow.

Hereditary Spherocytosis

• Etiology:
  • Autosomal dominant trait.
  • Genetic abnormality of proteins (spectrin or ankyrin) responsible for RBCs shape.
• Clinical features:
  • Positive family history.
  • Presents in newborn (50% of cases) with anemia and jaundice that may need exchange transfusion and phototherapy.
  • Other manifestations of chronic hemolytic anemia.
  • Pigment stones may lead to obstructive jaundice.
  • Splenomegaly.
• Investigations:
  • Laboratory data of chronic hemolytic anemia.
  • Anemia: mild to moderate.
  • MCV: usually normal.
  • MCH: raised.
  • Reticulocytosis.
  • Peripheral blood smear: shows spherocytes.
  • Osmotic fragility test: shows increased fragility of spherocytes in hypotonic saline.

Treatment of Hereditary Spherocytosis

• Splenectomy: recommended after age 5-6 years to avoid the risk of postsplenectomy sepsis in younger children.
• Folic acid supplement: 1mg/day.
• With severe anemia, aplastic crisis, and poor growth: repeated transfusions are necessary.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

• Etiology:
  • Sex-linked recessive mode of inheritance.
  • G6PD enzyme is necessary to prevent oxidant damage of the RBCs.
  • Hemolysis does not occur spontaneously but after exposure to certain drugs, ingestion of fava beans, inhalation of pollens of fava plant (favism), and infections.
• Agents precipitating hemolysis:
  • Antibacterials.
  • Vitamin K analogs.
  • Acetylsalicylic acid.
  • Chemicals: Naphthalene and benzene.
  • Illness: DM, hepatitis.
• Clinical manifestations:
  • Acute onset of pallor, jaundice, red urine, and fever within 48 hours of exposure to precipitating factors.
  • Anemic heart failure or acute renal failure may also occur.
• Diagnosis:
  • Indirect evidences of hemolysis.
  • Marked anemia.
  • Supravital preparation of the red cells: reveals Heinz bodies.
  • Reticulocytosis during recovery.
  • Unconjugated hyperbilirubinemia.
  • Hemoglobinuria.
  • Direct measurement of the enzyme activity.

Treatment of G6PD Deficiency

• Prevention of hemolysis by avoiding the offending agents.
• Acute attack:
  • Blood transfusion.
  • Fluid and alkali therapy to avoid renal failure.