Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by inherited defects in the red blood cell membrane. It is characterized clinically by varying degrees of anemia, jaundice, and splenomegaly. Peripheral blood typically shows an increased number of spherocytes and elevated red blood cell osmotic fragility.
Etiology and Pathogenesis
Approximately 75% of cases follow an autosomal dominant inheritance pattern, while 15% are autosomal recessive. Sporadic cases without a family history may result from gene mutations. The pathological basis lies in genetic abnormalities of red blood cell membrane proteins, leading to defects in cytoskeletal proteins. This results in lipid loss from the cell membrane, a reduction in membrane surface area, and the formation of spherocytes. The deformability and flexibility of spherocytes are diminished, making them more susceptible to destruction as they pass through the spleen, resulting in extravascular hemolytic anemia. The spleen not only sequesters and destroys spherocytes but also creates an inhospitable microenvironment for their survival. Conditions such as low pH, low glucose, reduced ATP levels, and locally high concentrations of reactive oxygen species produced by adjacent macrophages can further damage the cell membrane. This accelerates the destruction of spherocytes in the spleen.
Clinical Manifestations
HS can develop at any age. Anemia, jaundice, and splenomegaly are its most common clinical features. The severity of the manifestations varies due to differences in inheritance patterns and the degree of membrane protein defects. Common triggers include infections, and prolonged strenuous physical activity can worsen hemolysis. Common complications include gallstones (50%), while less common ones include recurrent leg ulcers, chronic erythema nodosum, gout, and extramedullary hematopoietic masses. Severe cases may experience hemolytic crisis or aplastic crisis, often triggered by infection. Additionally, insufficient dietary folate intake or increased folate demand by the body can precipitate megaloblastic anemia crises.
Diagnosis
The diagnosis relies on symptoms, signs, and laboratory findings indicative of chronic extravascular hemolysis. Increased numbers of spherocytes in the peripheral blood (>10%) and elevated red blood cell osmotic fragility, in combination with a positive family history, support a definitive diagnosis. In cases with no family history, secondary spherocytosis caused by conditions such as autoimmune hemolytic anemia must be excluded. For some atypical cases, additional diagnostic tests may be required, such as the eosin-5-maleimide binding test, red blood cell membrane protein component analysis, and membrane protein gene mutation analysis.
Treatment
The primary treatment for HS is splenectomy. After surgery, 90% of patients experience improvement in anemia and jaundice, although spherocytes persist. The most significant complication of splenectomy is infection, particularly pneumococcal sepsis (especially in children under 6 years old). Another potential complication is ischemic heart disease. Consequently, indications for splenectomy require careful consideration, and the procedure should ideally be delayed until after the patient reaches 6 years of age in pediatric cases. Laparoscopic surgery is the preferred approach. Routine pneumococcal vaccination is necessary before and after the operation. For severe anemia, red blood cell transfusions may be required. Folate supplementation is essential to prevent folate deficiency, which could exacerbate anemia or precipitate a crisis.
The prognosis for HS is generally favorable, with only a small number of cases resulting in death from a hemolytic crisis or post-splenectomy complications.