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Hereditary Spherocytosis

Hereditary Spherocytosis. Definition of Hereditary Spherocytosis (HS). A genetic disorder of the red blood cell membrane Characterized by: Anemia Jaundice Splenomegaly. Incidence of HS. Most common hereditary hemolytic anemia Northern European descent have more cases

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Hereditary Spherocytosis

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  1. Hereditary Spherocytosis

  2. Definition of Hereditary Spherocytosis (HS) • A genetic disorder of the red blood cell membrane • Characterized by: • Anemia • Jaundice • Splenomegaly

  3. Incidence of HS • Most common hereditary hemolytic anemia • Northern European descent have more cases • 1:5000 people in US • “silent” carrier state in 1.4% of population • Occurs worldwide but at an unknown rate of incidence

  4. Incidence of HS • Typically it is autosomal dominant trait • Autosomal recessive mode also occurs • Apparently health parents have more than one child affected • 20-25% of all HS cases • Often associated with severe hemolytic anemia

  5. Etiology of HS • Genetic defect causes defects in membrane proteins • Hemolysis results from • Interplay of intact spleen • Intrinsic membrane protein defect • Abnormal RBC morphology

  6. Pathophysiology • HS erythrocytes are caused by membrane protein defects resulting in cytoskeleton instability • Spectrin deficiency leads to loss of erythrocyte surface area, which produces spherical RBCs • Spherocytic RBCs are culled rapidly from the circulation by the spleen. • Splenomegaly occurs

  7. Pathophysiology • 4 abnormalities of red cell membrane proteins have been identified • Spectrin deficiency • Most common • Combined spectrin and ankyrin deficiency • Band 3 deficiency • Protein 4.2 defects Each has a variety of mutations which determines clinical presentation

  8. Spectrin Deficiency • Mutations of alpha-spectrin associated with recessive forms of HS • Occurs 3 times more often than beta-spectrin • Mutations of beta-spectrin associated with autosomal dominant forms of HS

  9. Ankyrin Defects • HS is described in patients with translocation of chromosome 8 or deletion of the short arm of chromosome 8 • Ankyrin gene located here • Principal binding site for Spectrin on RBC membrane • 75-80% of HS patients with autosomal dominant type have combined spectrin and ankyrin deficiency and the 2 proteins are diminished equally

  10. Band 3 Deficiency • 10-20% of patients with mild-moderate autosomal dominant HS • Deficiency is greater in older RBC’s • Suggests that Band 3 protein is unstable

  11. Protein 4.2 deficiency • Complete deficiency noted in patients with hereditary hemolytic anemia • This type of deficiency that leads to HS significant in Japan

  12. Clinical Presentation • Anemia • Usually mild-moderate • Can be severe • Not at all • Jaundice • Most prominent in newborns • Exchange transfusion required at times • Icterus is intermittent • Occurs with fatigue, cold exposure, stress, pregnancy • Splenomegaly • Detected in more than 75% of cases

  13. Diagnosis • Based on clinical findings and history • Pallor • Jaundice • Splenomegaly • RUQ pain • Family History of HS • history of a family member having had a splenectomy or cholecystectomy before the fourth decade of life • Any patient who presents with profound and sudden anemia and reticulocytopenia with the aforementioned physical findings also should have HS in the differential diagnosis

  14. Diagnosis • Lab work would show • Anemia • Reticulocytosis • Elevated MCHC • Low MCV • Incubated osmotic fragility test • Most sensitive • Complete hemolysis occurs of HS cells • RUQ US • r/o cholecystitis or cholelithiasis

  15. Treatment • Neonates with severe hyperbilirubinemia d/t HS • Risk for kernicterus • Phototherapy • Exchange transfusion as clinically indicated • Folic Acid-1mg/day for life • Sustains erythropoiesis • Splenectomy • Curative, but not always • Indicated for children over 6 years old • Fatal sepsis 200 x greater in kids less than 6 • Partial splenectomy possible • Retains immunologic function • Reduces rate of hemolysis

  16. Prognosis • After splenectomy, RBC survival improves dramatically, enabling most patients with HS to maintain a normal hemoglobin level

  17. References Emedicine from webMD (2010). Hereditary Spherocytosis. Retrieved from http://emedicine.medscape.com/article/206107-overview. March 29, 2010. MedicineNet.com (2010). Hereditary Spherocytosis. Retrieved March 29, 2010 from http://www.medterms.com/script/main/art.asp?articlekey=3724

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