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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

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