Hemolytic Anemia

Hemolytic Anemia

• Definition: Premature destruction of RBCs, resulting in anemia due to shortened survival of RBCs.
• Normal lifespan of RBCs: 100-120 days.
• Normally, 1% of RBCs are removed from circulation each day and replaced by equal numbers of new cells from the bone marrow.

General Features

• Anemia: Degree of anemia depends on rate of hemolysis and efficiency of bone marrow.
• Jaundice: Unconjugated hyperbilirubinemia due to bilirubin overload, usually mild as liver can increase conjugation capacity.
• Hepatosplenomegaly: Due to hemosiderosis and extramedullary hematopoiesis.
• Skeletal manifestations: Hyperplasia of erythropoietic tissue, leading to expansion of medullary spaces in skull and hands, abnormal mongoloid facies, prominence of malar eminences, frontal bossing, and depression of the nose and exposure of upper central teeth.

Investigations

• Indirect evidences of hemolysis:
  • Sustained reticulocytosis with low hemoglobin level.
  • Lowering or reversal of myeloid/erythroid ratio in bone marrow due to erythroid hyperplasia.
  • Blood chemistry: unconjugated hyperbilirubinemia, increased serum iron, decreased iron binding capacity, and decreased plasma concentration of haptoglobin and hemopexin.
  • Stool: increased stercobilinogen.
  • Urine: increased urobilinogen.
  • X-ray findings: hair-on-end appearance on skull radiograph, loss of waist of metacarpal bones, and rarefaction.
• Direct evidences of hemolysis:
  • Determination of RBC life span using radioactive chromium (51Cr) tagged RBCs.
  • Identification of free hemoglobin in plasma and urine.

Complications of Hemolytic Anemia

• Hemosiderosis and increased body iron: due to shortened life span of RBCs, frequent blood transfusion, and increased intestinal iron absorption.
• Manifestations of hemosiderosis:
  • Myocardium: uncontrolled heart failure.
  • Liver: liver cirrhosis.
  • Endocrinal dysfunction: pancreatic dysfunction, pituitary affection, gonadal dysfunction, adrenal gland affection, thyroid and parathyroid dysfunction.
• Gallstones: pigmented gallstones formed of calcium bilirubinate, usually developing after age 4.
• Anemic heart failure.
• Complications of blood transfusion: hepatitis, AIDS.
• Aplastic crisis: episodes of bone marrow failure, usually precipitated by viral infection.
• Hypersplenism: enlarged spleen with increasing demand for blood transfusion, depression of one or more cellular elements of blood.

Hereditary Spherocytosis

• Etiology: autosomal dominant trait, due to genetic abnormality of proteins (spectrin or ankyrin) responsible for RBC shape.
• Deficiency of these proteins results in loss of membrane surface area, increased cation permeability, and decreased deformability of spherocytic RBCs.
• Clinical features:
  • Positive family history.
  • Presents in newborn with anemia and jaundice.
  • Other manifestations of chronic hemolytic anemia.
  • Splenomegaly.
• Investigations:
  • Laboratory data of chronic hemolytic anemia.
  • Anemia, usually mild to moderate.
  • Reticulocytosis.
  • Peripheral blood smear: spherocytes.
  • Osmotic fragility test.

Glucose 6 Phosphate Dehydrogenase (G6PD) Deficiency

• Sex-linked recessive mode of inheritance.
• G6PD enzyme is necessary to prevent oxidant damage of RBCs.
• Hemolysis does not occur spontaneously, but after exposure to certain drugs, ingestion of fava beans, inhalation of fava plant pollens, and infections.
• Agents precipitating hemolysis in G6PD deficiency:
  • Antibacterials.
  • Vitamin K analogs.
  • Acetylsalicylic acid.
  • Chemicals: naphthalene and benzene.
  • Illness: DM and 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 occur.