Thalassemia

Question 1

Normal Hemogblobin
HbF (alpha2gamma2)
HbA (alpha2beta2)
HbA2 (alpha2delta2)

proportions at birth and 2yr

Answer 1

Birth
HbF 60-90%
HbA 10-40%
HbA2 95%
HbA2

Question 2

Why is it important to be able to diagnose a bambino with sickle cell even though they can use fetal until around 6 mos?

Answer 2

Because they frequently have infarcts - which messes up their spleen - so even though bambinos with sickle may not show sickle traits until 6mos they can have infections

Question 3

How do you prevent infections in bambinos with sickle?

Answer 3

Give penicillin

Question 4

Qualitative hemoglobinopathies

Answer 4

HbS
HbC
HbE

Question 5

All qualitative hemoglobinopathies are a consequence of ?

Answer 5

Beta chain issues

Question 6

Quantitative hemoglobinopathies

Answer 6

alpha thalassemia
beta thalassemia

gamma
delta

Question 7

Hemoglobin S
Homozygous?
Heterozygous?
Syndromes?

Answer 7

Homo = SS disease
Hetero = AS, sickle trait
Sickle syndromes
- Hemoglobin SC hemoglobinopathy 
- SBo thalassemia
- SB+ thalassemia

Question 8

Hemoglobin C

3

Answer 8

Homozygous CC hemoglobinopathy
Heterozygous C, e.g. AC, or C trait
C-beta thalassemia

Question 9

Hemoglobin E

Answer 9

Homozygous E
Heterozygous AE
Combination: E-beta thalassemia

Question 10

What is hemoglobin E

Answer 10

one of the most common mutated forms of hemoglobin in SE Asia
Asymptomatic unless express with beta thalassemia

Question 11

Hemoglobinopathies

Carriers in world

Answer 11

269 million

0.5%ish

Question 12

What percent of Africans are S carriers?

Answer 12

15

Question 13

What percent of SE Asians are E carriers?

Answer 13

7%

Question 14

What percent of SE Asian and Mediterranean are beta thal carriers?

Answer 14

4-5%

Question 15

How many babies are born with major hemoglobin disorder / year?

Answer 15

350,000

Majority die undiagnosed, untreated, or undertreated

Question 16

Where is SS distributed?

Answer 16

Mid Africa

Question 17

Where is HbC?

Answer 17

West Africa

Question 18

Where is thalassemia

Answer 18

Southern Eurasia / North Africa

Question 19

Where is HbE

Answer 19

SE Asia

Question 20

Why the distribution of Hemoglobinopathies?

Answer 20

Protect against malaria

Question 21

Hemoglobin mutations by region

SE Asia?

Answer 21

alpha thalassemia
beta thalassemia
and HbE

Question 22

Mutations by region

Africa?

Answer 22

HbS
HbC
alpha thalassemia
beta thalassemia

Question 23

Mutations by region

West Pacific

Answer 23

alpha thalassemia
beta thalassemia
HbE

Question 24

Mutations by region

East Meditteranean

Answer 24

Beta thalassemia

HbS

Question 25

Thalassemia | Definition

Answer 25

a disorder in which a reduced rate of one or more of the globin chain synthesis lead to imbalanced globin chain production, defective hemoglobin production, and damage to RBCs and their precurssors

Question 26

Thalassa | emia

Answer 26

Thalassa - sea | emia - blood

Question 27

5 types of alpha thalassemia

Answer 27

alpha thalassemia major (no alpha globin) alpha thalassemia 3 gene deletion (HgbH disease) alpha thalassemia 2 gene deleation (alpha thalassemia trait) alpha thalassemia 1 gene deletion (clinically insignificant) alpha thalassemia + Hgb constant spring

Question 28

Beta thalassemia (5)

Answer 28

Beta thalassemia major (Cooley's anemia) beta thalassemia intermedia bet thalassemia trait SBo thalassemia SB+ thalassemia

Question 29

2 Mechanisms of RBC destruction in thalassemia?

Answer 29

Ineffective erythropoeisis | Hemolysis

Question 30

Ineffective erythropoeisis

Answer 30

can't make good RBCs (intramedullary) excess of alpha or beta chains --> inclusion bodies (protein aggregate) --> apopotosis

Question 31

Hemolysis

Answer 31

abnormal RBCs targetet for destruction

Question 32

beta thalassemia minor (beta thalassemia trait) | 2 beta genes?

Answer 32

1 normal | 1 abnormal

Question 33

beta thalassemia minor | degree of anemia?

Answer 33

none-mild

Question 34

beta thalassemia minor | MCV?

Answer 34

Low-normal | low

Question 35

Beta thalassemia minor | Transfusion dependent?

Answer 35

No

Question 36

Beta thalassemia intermedia | 2 beta genes?

Answer 36

2 mildly-moderately abnormal genes

Question 37

Beta thalassemia intermedia degree of anemia? MCV? Transfusion?

Answer 37

degree = mild-moderate MCV = low Transfusion? - sometimes

Question 38

Beta thalassemia major (Cooley's anemia) | 2 beta genes?

Answer 38

2 severely abnormal or absent

Question 39

Beta thalassemia major (Cooley's anemia) degree of anemia? MCV? Transfusion?

Answer 39

degree of anemia - severe MCV = low Transfusion - always

Question 40

Clinical features of Cooley's anemia? (

Answer 40

``` Dense skull / marrow expansion - Enlarged spleen Osteopenia / bone changes Iron overload Growth and endocrine failure ```

Question 41

Treatment for Cooley's

Answer 41

``` Red cell transfusions Iron chelators Vitamin C Splenectomy/cholecystectomy Bone marrow transplant ```

Question 42

If you see FABarts (abnormal tetratmer made by 4 gamma chains) what should you think of?

Answer 42

Alpha thalassemia | excess of gamma chains (not enough alpha to pair up with)

Question 43

When you see HbA2, what should you think of?

Answer 43

Beta thalassemia | Not beta to pair up with

Question 44

``` alpha thalassemia trait (silent carrier) genotype degree of anemia MCV Transfusion? ```

Answer 44

``` genotype = - a / a a anemia = none MCV = normal Transfusion = no ```

Question 45

``` alpha thalassemia trait (2 genet deletion) genotype degree of anemia MCV Transfusion? ```

Answer 45

``` genotype = - - / a a or - a / - a Anemia = none-mild MCV = low normal / low Transfusion = no ```

Question 46

``` Hemoglobin H disease genotype degree anemia MCV Transfusion ```

Answer 46

``` genotype = - - / - a anemia = moderate - severe MCV = low Transfusion = sometimes ``` EXCESS OF BETA tetramers

Question 47

``` Hydrops fetalis genotype degree anemia MCV Transfusion? ```

Answer 47

genotype - - / - - | incompatible with life

Question 48

which chromosome codes alpha?

Answer 48

16