Lecture 13 Chapter 25

Question 1

What is the difference/similarity between hemoglobinopathies and thalassemias

Answer 1

Similarity: globulin chains are effected
Difference: hemoglobinopathies = single point mutation
Thalassemias = deletion of genes (genes are being deleted or are not being expressed)

Question 2

How do people with thalassemia have different severities?

Answer 2

It is like a dimmer switch; can have a mutation that you will still produce the globulin chain but at a much lower rate. That mutation will effect the subsequent symptoms. Or you may have the gene intact inplace without a mutation, but you may have a mutation in the promotor of the gene. If promotor cannot do its job, it wont matter that the gene is intact because the gene cannot be expressed. Majority is deletion

Question 3

What is the cause of a-thalassemia and when does it occur

Answer 3

Unable to make the alpha chain
Problems show up in utero

Question 4

What is the cause of b-thalassemia and when does it occur

Answer 4

Unable to make beta chain
Problems occur 6 - 12 months after birth

Question 5

What are thalassemias?

Answer 5

An imbalance in the globulin chains

Question 6

What happens when there is a globulin chain imbalance

Answer 6

Causes globulin chains to precipitate. Macrophages do not like any type of precipitation, so they remove the imbalanced globulin chains, causing anemia

Question 7

What are the two b-thalassemia genes

Answer 7

B-thalassemia minor
B-thalassemia major (100x worse than minor)

Question 8

What are the 4 a-thalassemia genes

Answer 8

A-thalassemia silent (missing 1)
A-thalassemia minor (missing 2)
A-thalassemia intermedia (hgb h) (missing 3)
A-thalassemia major (hydrops fetalis) (missing 4): will die in utero or very soon after birth

Question 9

What kinds of cells are seen in thalassemias

Answer 9

Target cells - thalassemias reduce production of hemoglobin → imbalance between the surface area and volume = less hemoglobin in RBCs means smaller volume in cells with a normal cell’s surface area (too much)

Question 10

What types of cells are seen with thalassemias

Answer 10

Microcytic, hypochronic
RBC inclusions
Basophilic stippling

Question 11

What controls the expression of the gene but is not part of the gene

Answer 11

Enhancers and promoters

Question 12

Name the types of mutation

Answer 12

Question 13

What is the main cause of thalassemias

Answer 13

Deletion

Question 14

What are the 4 syndromes of b-thalassemia and their characteristics

Answer 14

B-thalassemia silent carrier = mutations in genes that do not significantly reduce production of the globulin chain
B-thalassemia minor = No blood transfusion, minor anemia symptoms
B-thalassemia intermedia = Mutation still produces some globulin chains but not a lot
B-thalassemia major = frequent blood transfusions, more likely to get an iron overload

Question 15

What is the reticulocyte count in a thalassemic patient?

Answer 15

It would be elevated if you don’t correct for anemia. If corrected, count would be normal

Question 16

What happens to those born with B-thalassemia major?

Answer 16

They have no Hgb A which are what adults have most of. Expression of Hgb F may prolong they can be given medications to increase the expression of Hgb F. Oxygen must be carried by either delta, A2, gamma, or Hgb F

Question 17

What does this hair-like image on the skull indicate?

Answer 17

The medullary cavity in the bone marrow is expanding in order to accommodate making more cells

Question 18

What kind of hematopoiesis is thalassemia

Answer 18

Ineffective

Question 19

How can you determine the size of a RBC next to a small lymphocyte

Answer 19

Small lymphocyte’s nucleus are typically 7-9 nm and RBCs are typically 6-8 nm

Question 20

What will the blood smear look like for b-thalassemia major

Answer 20

+4 target cells
+4 poikilocytosis (elliptocytes, schistocytes, tear drops, spherocytes)
+4 anisocytosis
nRBCs
Hypochromic, microcytic
Basophilic stippling, HJ bodies, pappenheimer bodies

Question 21

What is the status of iron and ferritin in those with thalassemia

Answer 21

Iron will be normal, gets recycled after cell is destroyed
Ferritin could be elevated

Question 22

What is megaloblastic crisis

Answer 22

Can happen to those with thalassemia that are making a lot of RBCs and run out of folate

Question 23

What is the genotype and no. of genes present normally for alpha

Answer 23

aa/aa
4 genes

Question 24

What is the genotype and no. of genes present for a silent carrier

Answer 24

aa/-a
3 genes

Question 25

What is the genotype and no. of genes present for the a-thalassemia trait

Answer 25

-a/-a or aa/- -
2 genes

Question 26

What is the genotype and no. of genes present for Hgb H

Answer 26

-a/- -
1 gene

Question 27

What is the genotype and no. of genes present for Hgb Barts / hydrops fetalis

Answer 27

• -/- -
  0 genes

Question 28

What develops when you have Hgb H

Answer 28

Beta tetromeres that last 15 days because there is not enough alpha

Question 29

A patient has a problem in utero with creating alpha, what happens to the hgb?

Answer 29

There is no beta in utero, so without alpha, Hgb F becomes a tetromere of gammas, and Bart’s will precipitate. This causes the child to die in utero or die right after birth

Question 30

Label the a-thalassemias

Answer 30

Question 31

What disease and stain

Answer 31

Hemoglobin H
Supravital stain

Question 32

Disease and blood smear type

Answer 32

Mother with hemoglobin H
Severe anemia, poikilocytois, microcytic, hypochromic

Question 33

Disease and blood smear type

Answer 33

Still born fetus with hemoglobin Bart’s
Anisocytosis, Hgb H, RBC inclusions

Question 34

What happens if one parent with the thalassemia trait (B/B0) and one with the sickle cell anemia trait (Bs/B) have a child that inherits both genes (Bs/B0)

Answer 34

The child will have a more severe sickle cell anemia since they do not have one normal B gene

Question 35

What happens if a child is born with the sickle cell trait (B/Bs) on chromosome 11 and is missing 2 alpha genes on chromosome 16

Answer 35

You will have a reduction of production in both alpha and beta, so the symptoms are minimized.
Not transfusion dependent
The degree of difference is now less: no extra beta sitting and no extra alpha precipitating
(Aka compound heterozygous)

Question 36

What is the result if someone has b-thalassemia and Hgb C - thalassemia

Answer 36

Severe anemia

Question 37

What is the result if someone has a-thalassemia and Hgb C - thalassemia

Answer 37

Symptoms are lessened

Question 38

What is the result if someone has Hgb E and Hgb S

Answer 38

Symptoms: very severe anemia

Question 39

What is the result if someone has b-thalassemia and Hgb E - thalassemia (Be/B0)

Answer 39

Presents itself as homozygous E

Question 40

What is the result if someone has a-thalassemia and Hgb E - thalassemia

Answer 40

Symptoms = less

Question 41

Name the disease based on the gel electrophoresis results

Answer 41

Question 42

What is osmotic fragility

Answer 42

Trying to find out now easily we can make a RBC lyse/break apart

Question 43

What are some ways to test between IDA and thalassemia

Answer 43

1. Ferritin levels: IDA = low, thalassemia = elevated (however cannot rely on results b/c ferritin is an acute phase reactant)
2. Free erythrocyte protoporphyrin (FEP) or lead and zinc protoporphyrin (ZnPP) levels: IDA = goes up cause no iron, thalassemia = normal
3. RBC count: thalassemia = increase, IDA = decline
4. Mentzer index = MCV/RBC count (<13 = thalassemia; >13 = IDA)