Hematopoietic Systems: Hemolytic Anemia II

Anemia Classification

• Hemolytic anemias result from increased destruction of red blood cells (RBCs).
• Intrinsic abnormalities include hereditary disorders affecting RBC membrane, enzymes, and hemoglobin synthesis.
• Extrinsic abnormalities involve antibody-mediated destruction, mechanical trauma, and infections.

Intrinsic Abnormalities of RBCs

• Hereditary Conditions:

  • Disorders of RBC membrane cytoskeleton include spherocytosis and elliptocytosis.
  • Enzyme deficiencies such as glycolytic enzymes (pyruvate kinase, hexokinase) and those in the hexose monophosphate shunt (G6PD, glutathione synthetase).
  • Hemoglobin synthesis disorders like thalassemia syndromes (deficient globin synthesis) and sickle cell anemia (abnormal globin synthesis).

• Acquired Conditions:

  • Membrane defects like paroxysmal nocturnal hemoglobinuria.

Extrinsic Abnormalities

• Antibody Mediated:

  • Isohemagglutinins causing transfusion reactions and erythroblastosis fetalis (Rh disease).
  • Autoantibodies resulting from idiopathic causes, drug association, or systemic lupus erythematosus.

• Mechanical Trauma:

  • Microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura and disseminated intravascular coagulation (DIC).

• Infections:

  • Malaria can lead to hemolytic anemia.

Thalassemia

• Characterized by quantitative abnormalities in hemoglobin synthesis, categorized into:
  • α-thalassemia: Decreased synthesis of α-globin chains.
  • β-thalassemia: Either absent (β0) or reduced (β+) synthesis of β-globin chains.

Inheritance and Clinical Presentation

• Inherited as autosomal codominant traits.

  • Heterozygous (thalassemia minor): Generally asymptomatic or mild symptoms.
  • Homozygous (thalassemia major): Severe symptoms with hemolytic anemia.

• Commonly affects populations from Mediterranean, African, and Asian descent.

Normal Hemoglobin Structure

• Normal hemoglobin (HbA) is composed of 2 α and 2 β chains.
• α chains are produced by genes on chromosome 16; β chains are from a single gene on chromosome 11.

Clinical Classification of Thalassemias

• Thalassemia Major:

  • Homozygous β0-thalassemia requires regular blood transfusions.
  • Homozygous β+-thalassemia displays increased levels of fetal hemoglobin (HbF).

• Thalassemia Minor:

  • Heterozygous conditions are usually asymptomatic, with mild anemia and increased HbA2 production.

β-Thalassemia

• β0-thalassemia leads to total absence of β-globin chains.
• β+-thalassemia presents reduced, detectable β-globin synthesis with numerous mutations typically involving single base changes.

Pathogenesis of β-Thalassemia Major

• Results in hemolytic anemia due to reduced β-globin synthesis.
• Low overall hemoglobin formation, leading to hypochromic RBCs and hemolysis from excess α-globin.
• Ineffective erythropoiesis with destruction of immature RBCs in bone marrow and iron overload from increased dietary absorption.

Diagnosis of Thalassemia Major

• Peripheral Blood Smear:

  • Severe microcytic hypochromic RBCs, target cells, poikilocytosis, anisocytosis, and reticulocytosis.

• Hb Electrophoresis:

  • Shows reduced or absent HbA, elevated HbF, and normal or increased HbA2.

• Prenatal Diagnosis:

  • Achieved through DNA analysis.

Treatment Options

• Blood transfusions to alleviate skeletal deformities and prolong survival.
• Iron chelators used to manage iron overload.
• Early bone marrow transplantation is a potentially curative option.

This quiz covers Lecture III on Hemolytic Anemia, focusing on RBC disorders. It discusses classifications of anemia according to production mechanisms and the intrinsic abnormalities affecting red blood cells. Test your understanding of these critical hematological concepts.