Spherocytosis

Overview
Spherocytosis is an auto-hemolytic anemia (a disease of the blood) characterized by the production of red blood cells (RBCs), or erythrocytes, that are sphere-shaped, rather than donut-shaped or, more specifically, bi-concave disk shaped. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton (usually ankyrin, sometimes spectrin). Because the cell skeleton has a defect, the blood cell contracts to its most surface-tension efficient and least flexible configuration, a sphere, rather than the more flexible donut-shape. The sphere-shaped red blood cells are known as spherocytes.

Though the spherocytes have a smaller surface area through which oxygen and carbon dioxide can be exchanged, they in themselves perform adequately to maintain healthy oxygen supplies. However, they have a high osmotic fragility--when placed into water, they are more likely to burst than normal red blood cells. These cells are more prone to physical degradation. They are most commonly found in immunologically-mediated hemolytic anemias and in hereditary spherocytosis, but the former would have a positive direct Coombs test and the latter would not. The misshapen but otherwise healthy red blood cells are mistaken by the spleen for old or damaged red blood cells and it thus constantly breaks them down, causing a cycle whereby the body destroys its own blood supply (auto-hemolysis).

Symptoms
The spleen's hemolysis results directly in varying degrees of anemia and hyperbilirubinemia, which in turn result in symptoms of fatigue, pallor, and jaundice.

Acute cases can threaten hypoxemia through anemia and acute kernicterus through hyperbilirubinemia, particularly in newborns.

Chronic symptoms include anemia and splenomegaly, or enlargement of the spleen due to its increased activity. In some cases the spleen continues to change sizes. Yet in other cases the spleen just continues growing which puts the patient at a greater risk for rupture, which can cause death. Furthermore, the detritus of the broken-down blood cells--bilirubin--accumulates in the gallbladder, and can cause gallstones or "sludge" to develop. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis.

Diagnosis
In peripheral blood smears, many of the red blood cells will appear abnormally small and will lack the central pallor--the lighter area in the middle of a RBC as seen under a microscope.

The CBC (cell blood count) laboratory values will show elevated MCHC.

The splenic cords are congested with red blood cells to be destroyed and macrophages of the spleen will show signs of actively destroying erythrocytes (erythrophagocytosis). This will result in an elevated bilirubin level.

The bone marrow in its role of manufacturing red blood cells will display hyperplasia, the increased activity of replacing RBCs. As a result, immature red blood cell-or reticulocyte-counts will appear elevated.

Treatment of acute symptoms
Acute symptoms of anemia and hyperbilirubinemia can indicate treatment with blood transfusions or exchanges. Transfusions treat anemia by adding healthy donor blood to the patient's own, providing needed red blood cells. As the transfused blood does not contain elliptocytes, it will not be hemolysed per se, but the overactive spleen may still break down a significant proportion of the transfused blood. Exchanges treat hyperbilirubinemia by replacing some portion of the patient's blood with healthy donor blood, thus removing some portion of the toxic bilirubin.

Treatment of chronic symptoms
Chronic symptoms of anemia and splenomegaly typically indicate dietary supplementation of iron and eventual treatment by splenectomy, the surgical removal of the spleen.

Iron supplementation supports the increased production of red blood cells, but in longstanding cases in which patients have taken supplemental iron or received numerous blood transfusions, iron overload may be a significant problem, being a potential cause of cardiomyopathy and liver disease. If there is iron overload, chelation therapy with agents such as desferrioxamine may be necessary.

While splenectomy does not affect the shape of the blood cells, it does remove the more obvious physical symptoms of the disorder, as the blood cells are no longer constantly broken down. Though it offers near-immediate relief from symptoms, splenectomy is often not performed until the patient is in late childhood, so as not to hinder the patient's ability to fight off childhood infections. Currently, the surgery is often performed laparoscopically; this results in a shorter recovery time and a much smaller scar. Given that surgery is preplanned, it is highly recommended that patients receive prior Pneumovax-II pneumococcus, conjugated-C meningococcus & Haemophilus influenzae type b vaccinations to combat the patient's new lower tolerance against overwhelming post-splenectomy infection. The Pneumovax needs repeating every six years and the patient should have a yearly flu vaccine. Prophylactic antibiotics are also given. (See asplenia for further details on these measures).

Treatment of the disorder
Both measures described above treat the symptoms, not the cause of the disorder. Non-hereditary spherocytosis has several causes, each treated differently. Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans and because of the risks involved in human gene therapy, it may never be. See also Hereditary spherocytosis.