97. Congenital hemolytic anemias - classification, etiology, pathogenesis, clinical manifestations.

Congenital Hemolytic Anemias

Classification, Etiology, Pathogenesis, and Clinical Manifestations

Definition

Congenital hemolytic anemias are inherited disorders in which red blood cells (RBCs) are destroyed prematurely (hemolysis) due to intrinsic defects in their membrane, enzymes, or hemoglobin structure.

Classification

Etiology

Genetic mutations inherited in autosomal dominant or recessive patterns. Commonly found in populations where malaria was or is endemic (e.g., thalassemia, G6PD deficiency).

Pathogenesis

Membrane Defects (e.g., hereditary spherocytosis)

1. Mutation in spectrin, ankyrin, or band proteins → unstable membrane.
2. RBCs lose membrane fragments → become spherocytes.
3. These are less deformable → trapped and destroyed in spleen.

Enzyme Deficiencies (e.g., G6PD)

1. Defective enzymes reduce protection against oxidative stress.
2. Hemoglobin gets oxidized → Heinz body formation → RBC lysis.
3. Hemolysis is often episodic, triggered by infections or certain drugs/foods (e.g., fava beans).

Hemoglobinopathies (e.g., sickle cell anemia)

1. Mutation in β-globin gene → abnormal hemoglobin (HbS).
2. Under deoxygenation, HbS polymerizes → RBC sickling.
3. Sickled RBCs are rigid → obstruct capillaries → hemolysis and ischemic complications.

Clinical Manifestations

Laboratory Findings

• ↑ Reticulocyte count (compensatory response)
• ↑ LDH, indirect (unconjugated) bilirubin
• ↓ Haptoglobin

Peripheral smear: Spherocytes, elliptocytes, sickled cells, target cells (depending on the type)

Summary Table