Thalassemias Anemia pt2

Question 1

Describe the basic overview of Thalassemias
lifetime has ….

Answer 1

decreased production of one more more globulin chains (alpha or beta)

Lifetime has 6 normal hgb - 2 families of glob chains

Question 2

What is included in the Alpha chain family?

Beta chain family?

Answer 2

Alpha chain family: Alpha - zeta chains

Beta family: Beta, delta, gamma, epsilon

Question 3

What genes code for Hgb? what are their respective chains

Answer 3

Chromosome 16(alpha) and Chromosome 11 (Beta chains)

Question 4

T/F B chains are needed to form adult hgb

Answer 4

false, alpha chains are needed

Question 5

Describe Thalassemia
What is affected?
Increased?
Uncoup…

Disease states?

Answer 5

B chain production affected, Hgb A population affected

Increased Hgb A2/Hgb F to compensate

Uncoupling of A/B chain synthesis

Iron overload/bone deform

Question 6

Describe B chain Decreasing and what this causes

Answer 6

total Hgb is decreased and there is an accumulation of free A chains/denaturation and destroyed in BM

Question 7

Describe the genetic design in B thalassemia

B/B
B0
B+
B++S

Answer 7

B/B normal gene from each parent
B0 - abn no B chains produced
B+ - abn some/abn production of B chains
B++S - production >50% B chains (silent carriers)

Question 8

Describe B++s heterozygous
Mutation causes?
ratio

Answer 8

abnormal gene from one parent
Heterozygous Beta mutation only small decrease in B chain production

Normal A/B ratio

Question 9

Describe Homozygous B++s/B++s slient carrier
increased?

Answer 9

increased HgbA2/Hgb F

Question 10

Describe Beta Thalassemia minor
Genotype
anemia

increased what?

HIGH

Answer 10

Heterozygous B+/B B+/B0
One affected one normal
Mild/mod anemia

Increased HgbA2/Hgb F

HIGH BILIRUBIN/JAUNDICE
inc retics

Question 11

Describe Beta Thalassemia Major
Genotype
What types of Cells
Changes?

Hemolysis?

Answer 11

Homozygous B+/B+ B+/B0 B0/B0
B minor but more severe
Many nRBC
Marked bone changes/Expanded BM cavity

Hemolysis - free alpha chains (schistocytes)

Question 12

Describe Beta Thal Major Lab findings

Hematopoesis
Increased what?
inc hgb?

Prognosis
transfusions?
Drugs?

Answer 12

Extramedullary hematopoesis
Increased serum iron/ferritin
Increased Hgb A2/Hgb F

Grave prognosis
Transfusions/Iron overload/organ toxicity

Drugs with gamma genes

Question 13

Delta Beta Thalassemia
Similar to?

What can not be produced?

Increased?

Answer 13

Similar to Beta thalassemia intermediate
Hgb A/Hgb A2 can not be produced

Incr gamma chains/Hgb F

Question 14

Describe Hereditary Persist of fetal Hgb (HPFH)

Answer 14

Rare but similar to delta/beta thalassemia
Continued synthesis of high levels of Hgb F in adult life

Question 15

Describe Gamma-Delta-Beta-Thalassemia

Answer 15

Very rare, only in two families
ONLY HETEROZYGOTES
HOMO LETHAL

Question 16

Describe Hgb E

Answer 16

B chain defect with diminished production

Question 17

Describe Hgb lepore

Answer 17

Delta-Beta chain fusion with decreased production

Question 18

Describe Alpha chain family defects briefly

Answer 18

Alpha thalassemia
Alpha chain defect for alll adult Hgb. two genetic codes for production
Inherit 4 genes - two from each parent

Question 19

Describe Alpha thalassemia Silent Carrier (-X/XX)

Answer 19

One out of four alpha genes is defective
most patients are asymptomatic

Question 20

Describe Alpha thalassemia Minor (–/xx)(-x/-x)
Genotype
Appearance

Answer 20

Heterozygous 2 out of 4 alpha chain defects
Mild micro/hypo
Similar appearance/clinically to B-thal minor

Question 21

Describe Hgb H disease (–/-x)
Similar to?

Decreased/increased?

Answer 21

3/4 alpha chains defective
similar to Beta thal Major - tends to be milder

Decreased alpha chain production
Increased free beta chains - can form tetrameres

Question 22

Describe the Gamma4 tetramer (y4)

Beta4 Tetramer (B4)

Answer 22

Y4 - Hgb barts (trace amounts in adults)

B4 - Hgb H (unstable-forms heinz bodies, supravital stain “golf balls” Hgb H inclusions)

Question 23

Describe Hydrops Fetalis

Answer 23

All four genes are defective
Incompatible with life
Child is born w Hydrops Fetalis
VERY HIGH HGB BARTS (Y4) high affinity 02, child dies from hypoxia

Question 24

Alpha thal treatment

Answer 24

Blood transfusions/drugs/folic acid

Question 25

Describe Hgb Constant Spring

Answer 25

Alpha chain defects w/ diminished production

Question 26

Describe Thalassemia associated W/ structure Hgb varients

Hgb S
Hgb S
Hgb C

Answer 26

Thalassemia can be inherited w/ hemoglobinpathy

Hgb S/ B thal
Hgb S/ Alpha thal
Hgb C/ B thal

Question 27

Thalassemia Lab findings
Osm Frag
Suprav

Hgb Electro
Dec

What about Alpha thal

Answer 27

Osm fragility decreased
Supravital stain - heinz bodies
Hgb electrophoresis (critical for B thal diag)
(Dec Hgb A/ Incr Hgb A2)

more diff to detect Alpha thal
All norm hgb decreased