Hemoglobin disorders

Splenic Infarction and Complications

• Splenic infarction leads to an initially enlarged spleen, which becomes small and fibrotic with repeated infarctions, resulting in functional hyposplenism and increased susceptibility to infection.
• Ischemic damage can cause retinopathy, delayed puberty, avascular necrosis of the femoral head and humerus.
• Priapism can occur.

Sequestration Crisis

• A large amount of blood becomes acutely pooled in the liver and spleen, causing massive enlargement of these organs and signs of collapse.
• This crisis is a frequent cause of death in young infants.

Aplastic Crisis

• Parvovirus B19 infection can cause red cell aplasia, fever, pain, splenic sequestration, acute chest syndrome, glomerulonephritis, and strokes.

Hyperhemolytic Crisis

• Severe hemolysis, particularly with concomitant G6PD deficiency, can be precipitated by ingestion of an oxidant.

General Manifestations

• Chronic hemolytic anemia
• Liver impairment
• Spleen initially enlarged, then becomes small and fibrotic
• Increased susceptibility to infection (e.g., Salmonella osteomyelitis and H. influenzae meningitis)

Diagnosis

• Moderate to severe normochromic, normocytic anemia with reticulocytosis
• Indirect evidence of hemolysis
• Blood smear: sickle cells, nucleated red cells
• α-globin tetramers form, leading to red cell damage and hemolysis

Clinical Manifestations

• Onset usually in the 2nd half of the first year
• General features of chronic hemolytic anemia
• Failure to thrive in early childhood
• Pallor, jaundice, and gallstones
• Hepatosplenomegaly and hypersplenism
• Abnormal facies: prominence of malar eminence, frontal bossing, depression of bridge of nose, and exposure of upper central teeth
• Manifestation of hemosiderosis

Pathophysiology

• Single amino acid substitution: valine for glutamic acid in the beta-polypeptide chain
• HbS is less soluble than HbA
• Sickle cells are prematurely destroyed, causing hemolytic anemia
• Sickle cells result in increased blood viscosity and impaired blood flow, leading to thrombi

Crisis Types

• Vaso-occlusive or symptomatic crisis
• Sequestration crisis
• Aplastic crisis
• Hyperhemolytic crisis