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TRANSCRIPT
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Week 3: Hemoglobinopathies
Hemoglobinopathies
Thalassemia genetics
Hb synthesis Hb A, A2, F
Hb ELP
Hb Constant-Spring
Hb Barts Hb H
Hb Lepore
Hb E
Hb S
Hb C
Hb SC disease
HPFH
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Hemoglobinopathies
Decrease, lack of, or abnormal globin
May be severe hemolytic anemia
Abnormal Hb with low functionality
Mutation may be deletion, substitution,
elongation
Hb electrophoresis may be helpful
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Hemoglobin
Heme
Porphyrin ring and Fe
Globins
Alpha family on chromosome 16
]--//--[
Beta family on chromosome 11
]--//--[]--[[
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Thalassemia
1925: Described by Dr. Thomas Cooley and Dr. PearlLee of Detroit
1920s: Osmotic fragility test
1932: Dr. George Whipple of Rochester coined thename thalassa anemia from Greek story aboutXenophons army returning from Persia
1930s: Familial pattern recognized
1950s: Alkali denaturation test for Hb F, Hb ELP
1956: Coulter model A
1960s: RBC indices
1980s: Histogram, DNA analysis, PCR
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Signs and Symptoms
Hemolytic
Bone changes (hair on end)
Ethnicity: Mediterranean, Africa, SoutheastAsia
Hypo-Micro, Poikilocytosis
NRBCs, reticulocytosis, basophilicstippling
Siderocytes (with repeated transfusions)
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Thalassemia Blood Smears
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X-ray of scull
in Thalassemia:
Hair-on-end
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Perls iron stain (Prussian blue)
with potassium ferrocyanide
Siderocyte
Sideroblasts
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Thalassemia
Deletion of one or more alpha genes fromchromosome 16
-/: silent career with little signs
--/: cis double deletion more common in SEA
-/-: trans double deletion
--/-: Hb H disease
--/--: Hb Barts hydrops fetalis
Hb Constant-Spring: elongation (discovered inKingston, Jamaica; 2% of Thai have it)
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Thalassemia Lab Changes
High RBC
Low H&H and indices
High RDW
May need to rule out IDA
Hb ELP not useful except in Hb H
BCB prep for Hb H
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Hb H Prep with
Brilliant cresyl blue
thalassemia
Hydrops fetalis
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Peripheral blood smear: Hb H disease
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Thalassemia
Usually point mutation in the control region
+has minimal production
ohas no production +/+or o/ois thal major or Cooleys anemia
Often not apparent at birth until chain takes over
chain production High Hb A2, Hb F
Related: Hb Lepore (fusion), HPFH
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Hb F preparation with Kleihauer-Betke
Fetal Hb resists acid elution
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Hb S
Sickling Hb
Autosomal
Sickle crisis in low oxygen condition
6 glutamate to valine substitution
Prevalent in Eastern Africa
Solubility test
Sickling test (meta-bisulfite)
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Other Hemoglobinopathies
Hb C (6 Glu-Lys) in Western Africa
Cigar-like crystals
Billiard ball cells Folded cells
Hb SC disease
Washington monument cells
Mitten shape
Hb E (26 Glu-Lys) in SEA
Moves with Hb A2 in Hb ELP and A2 column
(ie, false elevated Hb A2)
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Hb SC diseaseHb C disease
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Unusual Hemoglobins in the World