![]() Reprinted with permission from Gallagher PG. The pathogenesis of the formation of elliptocytes in these syndromes is unknown.Ībbreviations: HS, hereditary spherocytosis HE, hereditary elliptocytosis HPP, hereditary pyropoikilocytosis NIHF, nonimmune hydrops fetalis SAO, Southeast Asian ovalocytosis. Glycophorin variants are also deficient in protein 4.1. Structural and functional defects of protein 4.1 appear to disrupt spectrin-actin contacts in the membrane skeleton. Spectrin integrity is critical for erythrocyte membrane stability and erythrocyte shape and function. Spectrin is composed of heterodimers of the related but nonidentical proteins α and β spectrin that self-associate into tetramers and higher-order oligomers. The majority of defects occur in spectrin, the principal structural protein of the erythrocyte membrane skeleton ( Figure 1). 1, 4, 18 These include α and β spectrin, protein 4.1 and glycophorin C. 2 Similar to HS, study of erythrocyte membrane proteins in these disorders has identified qualitative and/or quantitative abnormalities of various erythrocyte membrane proteins. The principal defect in HE/HPP erythrocytes is mechanical weakness or fragility of the erythrocyte membrane skeleton. Megaloblastic crisis occurs in patients with increased folate demands, e.g., the pregnant patient, growing children, or the elderly. ![]() Aplastic crisis may also be the event that brings an HS individual to medical attention, particularly the asymptomatic one with normally compensated hemolysis. In patients with severe HS, aplastic crisis may lead to severe anemia with serious complications including congestive heart failure or even death. Aplastic crises occur after virally induced bone marrow suppression, most commonly parvovirus B19. Common in children, they are typically associated with viral illness and rarely require intervention. Hemolytic crises are characterized by anemia, jaundice, increased splenomegaly, and reticulocytosis. 6 Hemolytic, aplastic, and megaloblastic crises may occur. 5 As in other inherited hemolytic anemias, recent studies have shown that co-inheritance of Gilbert syndrome increases the risk of neonatal jaundice and cholelithiasis in HS patients. Many of these patients are transfusion dependent.Ĭomplications of HS include cholelithiasis and associated problems including biliary obstruction, cholecystitis and cholangitis. These patients may develop complications of severe uncompensated anemia including growth retardation, delayed sexual maturation, and extramedullary “tumors,” skin ulcers, or thalassemic facies. Finally, a small group of HS patients have poorly compensated hemolysis and severe anemia. Most of these patients are asymptomatic except during times of increased erythroid stress, compensating for their hemolysis with increased erythropoiesis. ![]() About a quarter of HS patients have compensated hemolysis and little or no anemia. Splenomegaly is detectable in most older children and adults. Jaundice is seen at some time in about half of patients, usually in association with viral infections. The anemia is often asymptomatic except for pallor and/or fatigue. Most HS patients have incompletely compensated hemolysis and mild to moderate anemia. The degree of hemolysis varies widely, from asymptomatic patients who are diagnosed incidentally to severe, transfusion-dependent patients. “Typical” HS is marked by evidence of hemolysis with anemia, reticulocytosis, splenomegaly, jaundice, and gallstones, evidence of spherocytosis with spherocytes on peripheral smear and increased erythrocyte osmotic fragility, and a positive family history. Recent management guidelines acknowledge these important considerations when entertaining splenectomy and recommend detailed discussion between health care providers, patient, and family.Ĭlinical manifestations of the spherocytosis syndromes vary widely. Growing recognition and understanding of the long-term risks and complications of splenectomy, including cardiovascular disease, thrombotic disorders, and pulmonary hypertension, and the emergence of penicillin-resistant pneumococci, a concern for infection in overwhelming postsplenectomy infection, have led to reevaluation of the role of splenectomy. Splenectomy via a laparoscopic approach has become the surgical method of choice. Treatment with splenectomy is curative in most patients. This is particularly true for the spherocytosis syndromes where each kindred has a private mutation in one of the spherocytosis genes. Recent molecular studies have revealed that there is also significant genetic heterogeneity in these disorders. ![]() These syndromes are characterized by marked clinical and laboratory heterogeneity. Disorders of the erythrocyte membrane, including hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, and hereditary stomatocytosis, comprise an important group of inherited hemolytic anemias.
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