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PowerPoint Presentation - Week 3: Hemoglobinopathies

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  • 1. Week 3: Hemoglobinopathies  HemoglobinopathiesHemoglobinopathies  Thalassemia geneticsThalassemia genetics  Hb synthesisHb synthesis  Hb A, A2, FHb A, A2, F  Hb ELPHb ELP  Hb Constant-SpringHb Constant-Spring  Hb Bart’sHb Bart’s  Hb HHb H  Hb LeporeHb Lepore  Hb EHb E  Hb SHb S  Hb CHb C  Hb SC diseaseHb SC disease  HPFHHPFH
  • 2. Hemoglobinopathies  Decrease, lack of, or abnormal globinDecrease, lack of, or abnormal globin  May be severe hemolytic anemiaMay be severe hemolytic anemia  Abnormal Hb with low functionalityAbnormal Hb with low functionality  Mutation may be deletion, substitution,Mutation may be deletion, substitution, elongationelongation  Hb electrophoresis may be helpfulHb electrophoresis may be helpful
  • 3. Hemoglobin  HemeHeme  Porphyrin ring and FePorphyrin ring and Fe  GlobinsGlobins  Alpha family on chromosome 16Alpha family on chromosome 16 −−[ζ−−[ζ]--//--[]--//--[α2]−−[α1]−−α2]−−[α1]−−  Beta family on chromosome 11Beta family on chromosome 11 −−[ε−−[ε]--//--[]--//--[γγ]--[]--[γ]−−γ]−−[[δ]−−[β]−−δ]−−[β]−−
  • 4. Thalassemia  1925: Described by Dr. Thomas Cooley and Dr. Pearl1925: Described by Dr. Thomas Cooley and Dr. Pearl Lee of DetroitLee of Detroit  1920’s: Osmotic fragility test1920’s: Osmotic fragility test  1932: Dr. George Whipple of Rochester coined the1932: Dr. George Whipple of Rochester coined the name “thalassa anemia” from Greek story aboutname “thalassa anemia” from Greek story about Xenophon’s army returning from PersiaXenophon’s army returning from Persia  1930’s: Familial pattern recognized1930’s: Familial pattern recognized  1950’s: Alkali denaturation test for Hb F, Hb ELP1950’s: Alkali denaturation test for Hb F, Hb ELP  1956: Coulter model A1956: Coulter model A  1960’s: RBC indices1960’s: RBC indices  1980’s: Histogram, DNA analysis, PCR1980’s: Histogram, DNA analysis, PCR
  • 5. Signs and Symptoms  HemolyticHemolytic  Bone changes (hair on end)Bone changes (hair on end)  Ethnicity: Mediterranean, Africa, SoutheastEthnicity: Mediterranean, Africa, Southeast AsiaAsia  Hypo-Micro, PoikilocytosisHypo-Micro, Poikilocytosis  NRBC’s, reticulocytosis, basophilicNRBC’s, reticulocytosis, basophilic stipplingstippling  Siderocytes (with repeated transfusions)Siderocytes (with repeated transfusions)
  • 6. Thalassemia Blood Smears
  • 7. X-ray of scull in Thalassemia: “Hair-on-end”
  • 8. Perl’s iron stain (Prussian blue) with potassium ferrocyanide Siderocyte Sideroblasts
  • 9. α Thalassemia  Deletion of one or more alpha genes fromDeletion of one or more alpha genes from chromosome 16chromosome 16  --αα//αααα: silent career with little signs: silent career with little signs  --/--/αααα: cis double deletion more common in SEA: cis double deletion more common in SEA  --αα/-/-αα: trans double deletion: trans double deletion  --/---/-αα: Hb H disease: Hb H disease  --/--: Hb Bart’s hydrops fetalis--/--: Hb Bart’s hydrops fetalis  Hb Constant-Spring: elongation (discovered inHb Constant-Spring: elongation (discovered in Kingston, Jamaica; 2% of Thai have it)Kingston, Jamaica; 2% of Thai have it)
  • 10. α Thalassemia Lab Changes  High RBCHigh RBC  Low H&H and indicesLow H&H and indices  High RDWHigh RDW  May need to rule out IDAMay need to rule out IDA  Hb ELP not useful except in Hb HHb ELP not useful except in Hb H  BCB prep for Hb HBCB prep for Hb H
  • 11. Hb H Prep with Brilliant cresyl blue α thalassemia Hydrops fetalis
  • 12. Peripheral blood smear: Hb H disease
  • 13. β Thalassemia  Usually point mutation in the control regionUsually point mutation in the control region  ββ++ has minimal productionhas minimal production  ββoo has no productionhas no production  ββ++ //ββ++ oror ββoo //ββoo isis ββ thal major or Cooley’s anemiathal major or Cooley’s anemia  Often not apparent at birth untilOften not apparent at birth until ββ chain takes overchain takes over γγ chain productionchain production  High Hb A2, Hb FHigh Hb A2, Hb F  Related: Hb Lepore (Related: Hb Lepore (δ−βδ−β fusion), HPFHfusion), HPFH
  • 14. Hb F preparation with Kleihauer-Betke Fetal Hb resists acid elution
  • 15. Hb S  Sickling HbSickling Hb  AutosomalAutosomal  Sickle crisis in low oxygen conditionSickle crisis in low oxygen condition  ββ6 glutamate to valine substitution6 glutamate to valine substitution  Prevalent in Eastern AfricaPrevalent in Eastern Africa  Solubility testSolubility test  Sickling test (meta-bisulfite)Sickling test (meta-bisulfite)
  • 16. Other Hemoglobinopathies  Hb C (Hb C (ββ6 Glu-Lys) in Western Africa6 Glu-Lys) in Western Africa  Cigar-like crystalsCigar-like crystals  Billiard ball cellsBilliard ball cells  Folded cellsFolded cells  Hb SC diseaseHb SC disease  Washington monument cellsWashington monument cells  Mitten shapeMitten shape  Hb E (Hb E (ββ26 Glu-Lys) in SEA26 Glu-Lys) in SEA  Moves with Hb A2 in Hb ELP and A2 columnMoves with Hb A2 in Hb ELP and A2 column (ie, false elevated Hb A2)(ie, false elevated Hb A2)
  • 17. Hb SC diseaseHb C disease
  • 18. Unusual Hemoglobins in the World