Hereditary Spherocytosis

Hereditary spherocytosis is characterized by a membrane defect within red blood cells resulting in a shortened survival time. The red cells have low amounts of lipid within the bilayer membrane that lead to an abnormally small amount of surface area. Because the red blood cells are spherocytic, flow through the spleen is difficult, resulting in hemolysis. It is caused by an inherited metabolic defect.

Congenital Spherocytic Anemia; Minkowski-Chauffard Syndrome; Spherocytosis.

Hemolytic anemia caused by red blood cell membrane defect. Although a spectrin deficiency is seen in most hereditary spherocytosis patients, the principal defect is an abnormality of the RBC membrane protein ankyrin.

1:5000 in the general population; mainly in white populations originating from areas around the Mediterranean sea.

Autosomal dominant in most cases, but autosomal recessive forms exist (spectrin deficiency). Four subsets can be defined by the protein defect: (1) partial spectrin deficiency (mutations of alpha-spectrin are associated with recessive forms, whereas mutations of beta-spectrin produce autosomal dominant forms); (2) combined partial spectrin/ankyrin deficiency; (3) partial band 3 protein deficiency; and (4) protein 4.2 deficiency.

The protein abnormality causes defects in vertical stabilization of the phospholipid bilayer of the red cell membrane, which causes a separation of the spectrin-phospholipid bilayer. As a consequence, portions of the phospholipid bilayer form vesicles and thus are lost from the red blood cell (RBC) surface—the surface area is decreased and spherocytes are formed. These abnormal RBCs are retained in the spleen and destroyed, leading to anemia.

Based on clinical signs of anemia, analysis of the peripheral smear (numerous spherocytes), moderate anemia with reticulocyte count greater than 10%, and osmotic fragility test (which reflects the decreased surface-to-volume ratio of red blood cells). Erythrocytes also have increased autohemolysis, increased metabolic depletion of glucose, and increased mechanical fragility.

Symptoms can be quite variable. The erythrocytic fragility and hepatic enzyme immaturity may cause significant neonatal jaundice. Whether or not occasional acute aplastic crises (especially after parvovirus infection) is revealing; the clinical picture is mainly that of an anemia that may vary from mild to severe. Hyperbilirubinemia, predisposing to cholelithiasis, elevated plasma lactate dehydrogenase, splenomegaly, endocrine dysfunctions, and acute renal failure following hemolytic crisis, is not unusual. Splenectomy markedly improves anemia.

Obtain a complete cell blood count (CBC) and coagulation profile. In case of severe anemia, elective surgical procedures should be delayed until hemoglobin level has been corrected. For surgical procedures with the potential for large blood loss and fluid shift, preoperative blood cross-match must be obtained.

Oxygen-carrying capacity is the most important consideration associated with this medical condition. It is essential to prevent red cell hemolysis often caused by hyperdynamic cardiovascular responses. The prevention of hypothermia is also important to limit venous stasis, red cells fragility, and hemolysis. Glucose intravenous solutions must be administered to maintain red cells energy across the membrane and limit the possibility of spherocytosis.

No specific pharmacological implications associated with this medical condition.

Hereditary Elliptocytosis: Autosomal dominant hemolytic disease in which erythrocytes are elongated into either an oval or a bizarre poikilocytic shape as a consequence of mutation disrupting the formation of spectrin tetramers; at least four loci are implicated.

Hereditary Stomatocytosis: Series of inherited red blood cell disorders in which the outer membrane of the cell “leaks” sodium and potassium.

Hereditary Pyropoikilocytosis: Autosomal dominant hemolytic medical condition in which erythrocytes have a bizarre morphology similar to that seen in thermal burns. It is probably the result of co-inheritance of a mutation impairing spectrin association (and causing hereditary elliptocytosis) and a second mutation that results in quantitative spectrin deficiency.