Thalassemias

Question 1

When does alpha chain production begin?

Answer 1

Immediately, as it is required for fetal survival

Question 2

How long after birth does beta globin take over for gamma globin?

Answer 2

3-6 months

Question 3

Where is the alpha chain gene located?

Answer 3

Chrom 16

Question 4

Where is the beta chain gene located?

Answer 4

Chrom 11

Question 5

What type of Hb is common in alpha-thal?

Answer 5

Hb H

Hb Barts

Question 6

What type of Hb is common in beta-thal?

Answer 6

Increase F or A2

Question 7

What chain is defected in thal major usually?

Answer 7

Beta

Question 8

Where is beta-thal very common inthe world?

Answer 8

mediterranean

Question 9

Why does thal lead to anemia?

Answer 9

The poorly-produced beta chains cannot pair with the alpha chains. thus, the alpha chain is unpaired and forms hemichromes, which then mean the cell will undergo apoptosis.

Question 10

What are the three types of thal?

Answer 10

Major
Inmdt - 7-10g Hb that are normal
Minor - may have mild anemia

Question 11

What are signs of a person with thal major?

Answer 11

Very active bm, mishappen limbs, improper teeth formation, abnormal facial features (flat nose), massive hepatosplenomegaly (due to hemolytic anemia). Excessive pigmentation of skin

Question 12

How long do the RBCs live in thal?

Answer 12

30 days. So liver and spleen are enlarged bc it’s clearing wasted cell parts.

Question 13

Why does thal lead to increased susceptibility to bacterial infxns?

Answer 13

The iron is helpful to bacteria. Also, decreased healing due to impaired blood flow. Leg ulcers common in all types of hemolytic anemia, such as thal and sickle cell)

Question 14

Why is there iron overload in thal?

Answer 14

1. Transfusion iron
2. Increased iron absorption (ineffective erythropoeisis, decreased hepcidin, increased absorption and release of iron from macrophages)

Question 15

Why are people with thal hypercoagulable?

Answer 15

The normal RBC has phosphatidylserine on inside of cell membrane. When the membrane is damaged by alpha hemichromes and oxidant stress, the PS flilps to the outside, triggering apoptosis. Also, there is increased plasma free hb and platelet activation

Question 16

Why is thal associated with endocrine and bone disease?

Answer 16

Hypogonadism, pituitary insufficiency, osteopenia (bone marrow expansion, endocrine dysfunction, iron chelators)

Question 17

What are the clinical presentations of thal so variable?

Answer 17

The specific mutation leads to variable amounts of beta hemaglobin (B0 vs B+). Also, iron metabolism, bilirubin metabolsim and alpha hemoglobin stablizing protein. Many idfferent factors.

Question 18

What blood type is elevated in thal?

Answer 18

A2 Hb will be above 3.5%

Question 19

What is different above the microscopic appearance of cells in thal?

Answer 19

microcytic, hypochromatic, anisocytosis, poikilocytosis, (all like fe deficiency). also, increased basophilic staining because rapid abnormal blood production. Not exclusive to thal.

Question 20

Where do we see basophilic stippling?

Answer 20

Thal
hemolytic anemia
myelodysplastic syndrome/sideroblastic anemia
megalobastic anemia
heavy metal poisoning

Question 21

What are the most common diagnosis methods of thal?

Answer 21

HPLC or Electrophoresis. These cannot be used for alpha-thal however, which requires pcr

Question 22

What is hereditary persisntece of fetal hb?

Answer 22

Marked decreased in beta globin synthesis compensatecd by increase in gamma chain. S/HPFH OCCURS 1% as often as SS, and produced a favorable sickle syndrome.

Question 23

What is E/Beta-thal?

Answer 23

One beta globin gene with a thal gene and one carrying hb E gene. SE asian popular. Considered intermediate.

Question 24

What is hemoglobin lepore?

Answer 24

a dminished amount of non alpha chains under the control of the delta promoter which is much less vigorous than the beta promotrer, resulting in reduction of non alpha chains by 85-95% , leading to thal inter or major.

Question 25

What is alpha-thal?

Answer 25

Usually caused by gene deletion
Usually 4 copies of the alpha gene
Lose of 4 hydrops fetalis
3 Hb H disease
2 traits
1 silent carrier

Question 26

Describe Hb H?

Answer 26

Very high oxygen affinity, like CO. Some increased epo but no as extreme as beta-thal.

Question 27

What is Hb Constant Spring?

Answer 27

mRNA copies another 31 AAs, making unstable mRNA, leading to marked decraese in translation of alpha gene.