Spherocytosis is a condition where red blood cells, normally disc-shaped and flexible, become abnormally spherical. These altered cells, called spherocytes, are less pliable and more susceptible to premature destruction within the body. The fundamental issue in spherocytosis lies in the fragility and shortened lifespan of these unusually shaped red blood cells.
Understanding Spherocytes
Normal red blood cells have a biconcave disc shape, resembling a doughnut with an indented center. This structure and their flexible membrane allow them to easily navigate narrow blood vessels, delivering oxygen to tissues and carrying carbon dioxide away. Their flexibility enables them to change shape without breaking as they pass through tiny capillaries.
Spherocytes, in contrast, are sphere-shaped and lack the central pallor seen in healthy red blood cells. This spherical form results from defects in the red blood cell membrane, making them less deformable and more rigid. Consequently, these less flexible spherocytes struggle to pass through the spleen’s narrow passages, where they become trapped and prematurely destroyed. This accelerated destruction, known as hemolysis, leads to a shortage of red blood cells, contributing to anemia.
Causes of Spherocytosis
Spherocytosis can arise from two primary categories: hereditary and acquired. Hereditary spherocytosis (HS) is a genetic disorder resulting from mutations in genes responsible for producing proteins essential for the red blood cell membrane’s structure. These proteins include ankyrin, spectrin, band 3, and protein 4.2, and defects in them weaken the cell membrane, causing the spherical shape. Approximately 75% of hereditary spherocytosis cases are inherited in an autosomal dominant pattern, meaning only one copy of the altered gene is needed to cause the condition. About 25% are autosomal recessive or result from new spontaneous mutations.
Acquired spherocytosis develops later in life due to other underlying conditions. One common cause is autoimmune hemolytic anemia (AIHA), where the body’s immune system mistakenly produces antibodies that attack and damage its own red blood cells. Other conditions include severe burns, certain infections such as Clostridium perfringens sepsis, or transfusion reactions like ABO incompatibility.
Recognizing Spherocytosis
Symptoms of spherocytosis are linked to the premature destruction of red blood cells. Individuals may experience signs of anemia, such as persistent fatigue, pale skin, and shortness of breath, due to the reduced number of oxygen-carrying red blood cells. Jaundice, a yellowing of the skin and eyes, can also occur from the buildup of bilirubin, a yellow pigment released when red blood cells break down. An enlarged spleen (splenomegaly) is another frequent finding, as the spleen works overtime to filter out the abnormal spherocytes.
Diagnosis involves a physical examination and specific laboratory tests. A complete blood count (CBC) may indicate anemia, and a microscopic examination of a peripheral blood smear can reveal the characteristic spherical red blood cells. Further diagnostic tests include the osmotic fragility test, which assesses the spherocytes’ increased susceptibility to bursting in diluted solutions. The eosin-5-maleimide (EMA) binding test, a flow cytometry method, helps detect membrane protein deficiencies common in hereditary forms. Genetic testing can confirm specific gene mutations for hereditary spherocytosis, especially in cases where diagnosis remains uncertain.
Managing Spherocytosis
Management of spherocytosis focuses on alleviating symptoms and preventing complications. For mild cases, regular monitoring by a healthcare provider may be sufficient, as some individuals experience few or no symptoms. Folic acid supplementation is often recommended for all patients, as it supports the increased production of red blood cells needed to compensate for their premature destruction.
Blood transfusions are used for severe anemia or during acute aplastic crises, periods when red blood cell production significantly drops, often triggered by infections. For more severe cases, removal of the spleen (splenectomy) can significantly reduce hemolysis and improve anemia, as the spleen is the primary site where spherocytes are destroyed. Splenectomy carries risks, including increased susceptibility to certain infections, and is often delayed in children until after age five or six years to allow for immune system development. Untreated complications include severe anemia, gallstones due to chronic bilirubin excess, and recurrent aplastic crises.