Spherocytosis is a blood disorder characterized by a change in the shape of red blood cells (RBCs). Normally flexible biconcave discs, these cells become abnormally round, or spherical (spherocytes), losing their central pale area. This structural change compromises the cells’ ability to navigate small blood vessels and leads to their premature destruction. This shortened RBC lifespan ultimately causes a form of anemia.
Understanding the Red Blood Cell Defect
The spherical shape results from a flaw in the red blood cell’s membrane skeleton, which acts as the cell’s internal scaffolding. This skeleton is composed of proteins like spectrin, ankyrin, and band 3, which maintain flexibility and surface area. Deficiency or defects in these proteins destabilize the connection between the inner skeleton and the outer lipid bilayer.
This instability causes the cell to shed small pieces of its outer membrane, progressively reducing the surface area. Since the cell’s internal volume remains constant, it assumes the shape with the smallest possible surface area: a sphere. These rigid cells are less able to deform and squeeze through the tight passages within the spleen.
The spleen acts as a quality control filter for the blood. When it encounters rigid spherocytes, splenic macrophages recognize them as flawed and destroy them in a process called extravascular hemolysis. This accelerated destruction shortens the red blood cell lifespan from the normal 120 days to as few as 10 to 30 days, leading to chronic hemolytic anemia.
Causes and Inheritance Patterns
Spherocytosis is most often hereditary (Hereditary Spherocytosis or HS), caused by a genetic mutation affecting red blood cell membrane proteins. The condition’s severity often correlates with the specific protein deficiency. Defects involving spectrin and ankyrin are the most common and lead to the classical presentation of HS.
The disorder is typically inherited in an autosomal dominant pattern, requiring only one copy of the defective gene (75% of cases). Genes like ANK1, SPTB, and SLC4A1 are frequently implicated in this dominant form. A smaller number of cases are inherited in an autosomal recessive pattern, requiring two copies of the defective gene, often involving proteins like band 4.2.
While HS is the most common form, spherocytes can also appear in acquired conditions due to external factors. The most frequent acquired cause is Warm Autoimmune Hemolytic Anemia (AIHA), where the body produces antibodies that coat the red blood cells. When the spleen attempts to remove the antibody-coated membrane, it “bites off” a portion, turning the cell into a spherocyte.
Other, rarer acquired causes include severe burns or certain bacterial infections. The distinction between hereditary and acquired spherocytosis is important for diagnosis. Acquired spherocytosis often resolves when the underlying cause is treated.
Symptoms and Clinical Manifestations
Clinical signs arise directly from chronic red blood cell destruction and the body’s compensation efforts. Anemia is a primary manifestation, presenting as fatigue, pallor, and reduced exercise tolerance due to decreased oxygen capacity. The body counteracts this loss by accelerating production, a process called reticulocytosis.
Another common sign is jaundice, a yellowing of the skin and eyes, which occurs because of the rapid breakdown of hemoglobin. This breakdown releases large amounts of bilirubin, a yellow pigment that the liver struggles to process quickly.
The spleen often becomes noticeably enlarged (splenomegaly) as it is overworked filtering and destroying abnormal spherocytes. High concentrations of bilirubin in the bile increase the risk of forming pigmented gallstones, which can cause episodes of severe abdominal pain.
Patients are also susceptible to aplastic crises, typically triggered by an infection like Parvovirus B19, which temporarily halts red blood cell production in the bone marrow. In a person with a shortened red blood cell lifespan, this temporary stop can lead to a sudden and severe drop in hemoglobin levels.
Diagnosis and Confirmation
Suspicion of spherocytosis often begins with a routine blood test and a peripheral blood smear. The smear allows visual identification of the characteristic small, dense, spherical red blood cells that lack central pallor. An important clue is an elevated Mean Corpuscular Hemoglobin Concentration (MCHC), reflecting the cell’s reduced surface area relative to its volume.
A traditional confirmatory test is the Osmotic Fragility Test, which measures how easily red blood cells lyse when placed in a diluted saline solution. Because spherocytes have lost membrane surface area and are already swollen, they are much more fragile and burst more readily than normal red blood cells.
A more modern and specific method is the Eosin-5-Maleimide (EMA) binding test, which uses flow cytometry to confirm the membrane protein defect. This fluorescent dye binds specifically to the band 3 protein on the red cell surface. In spherocytosis, the defective membrane structure leads to a reduced number of band 3 binding sites, causing a measurably lower fluorescence intensity compared to normal cells, thereby confirming the diagnosis.
Treatment and Long-Term Management
Management depends on the severity, ranging from simple monitoring for mild cases to surgical intervention for severe disease. Supportive care involves daily supplementation with Folic Acid, a B vitamin necessary for DNA synthesis. Since the bone marrow constantly produces new red blood cells, the high demand for folate requires supplementation to prevent a deficiency that could worsen anemia.
For patients with moderate to severe symptoms (chronic anemia, recurrent crises, or painful splenomegaly), the most definitive treatment is a splenectomy (surgical removal of the spleen). Removing the spleen eliminates the primary site of red blood cell destruction, significantly increasing the lifespan of spherocytes and usually resolving the anemia.
The procedure carries risks, so total splenectomy is typically deferred until the child is over six years of age. This delay allows the immune system to develop sufficiently, as the spleen plays an important role in fighting certain types of infection.
Post-splenectomy patients face a lifelong, elevated risk of Overwhelming Post-Splenectomy Infection (OPSI) from encapsulated bacteria, such as Streptococcus pneumoniae. This requires prophylactic antibiotics and comprehensive vaccinations. Splenectomy also increases the long-term risk of developing thromboembolic events, specifically venous thrombosis, due to changes in blood composition.