1 / 17

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

kenna
Télécharger la présentation

Hereditary Spherocytosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related