Thalassemia Flashcards
How many alpha-globin genes are there?
What chromosome are they on?
4 genes (two on each)
Chromosome 16
How many beta-globin genes are there?
What chromosome are they on?
2 genes (one on each)
Chromosome 11
What is the major hemoglobin in a child of 6 months?
Hemoglobin A1
Is alpha thalassemia most often cause by dysfuctional gene or absence of gene?
Absence of gene
Having a two gene deletion in an alpha hemoglobin gene can be cis or trans. Which one is most commonly found in people of Asian descent?
Cis is most often found in people of Asian descent
Trans is most often found in people of African American descent
Why is hydrops fetalis more often found in people of Asian descent?
Because people of Asian descent are more often carriers of cis mutations. Two carriers of cis mutations have a 25% chance of having a fetus with hydrops fetalis –/–
Fill in the following characteristics for alpha-thalassemia trait:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
-a/–
No anemia
No MCV change
No
Fill in the following characteristics for alpha-thalassemia trait (2-gene deletion):
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
–/aa OR -a/-a
None-MIld
Low-Normal or Low
No
Fill in the following characteristics for Hemoglobin H Disease:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
–/a-
Moderate-Severe
Low
Sometimes
Fill in the following characteristics for Hydrops fetalis:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
–/–
Incompatible with life
Is hydrops fetalis curable?
Yes. With an in utero bone marrow transplant
Is beta thalassemia most often cause by dysfuctional gene or absence of gene?
Dysfunctional gene due to point mutations
What is Hemoglobin E?
A structurally abnormal hemoglobin, due to a point mutation in the Beta-globin gene at position 26 from glu–>lys
Is Hemoglobin E stable?
No. It is unstable
In which ethnic group is Hemoglobin in most commonly found?
Persons of southeast Asian descent
Fill in the following characteristics for Beta- Thalassemia minor:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
1 Normal Gene/ 1 Abnormal Gene
None-Mild
Low-Normal or Low
No
Fill in the following characteristics for Beta-Thalassemia Intermedia :
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
2 mildly-moderately abnormal genes
Mild-Moderate
Low
Sometimes
Fill in the following characteristics for Beta-Thalassemia Major (Cooley’s Anemia):
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
2 Severely Abnormal or absent genes
Severe
Low
Always
Fill in the following characteristics for HbEB+ Thalassemia:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
1 mildly-moderately abnormal Beta gene & 1 Hb E gene
Mild-Moderate
Low
Sometimes
Fill in the following characteristics for HbEB0 Thalassemia:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
1 severely abnormal or absent Beta gene & 1 Hb E gene
Severe
Low
Often
Fill in the following characteristics for 2 Hb E genes:
Genes:
Degree of Anemia:
MCV:
Transfusion Dependent?:
2 Hb E genes
Mild
Low
No
What disorders show characteristic low MCV, low MCHC, and target cells?
Alpha Thalassemia
Beta Thalassemia
Hemoglobin E
Iron deficiency
What is Hemoglobin Barts?
It is a tetramer of gamma
Occurs when –/-a
What is Hemoglobin H?
It is a tetramer of beta hemoglobin
Occure when –/-a
What hemoglobins increase in Beta Thalassemias?
Hemoglobin F
Hemoglobin A2
How would an eletroporesis of an individual with alpha-thalassemia appear?
Normal, because all hemoglovins would be underproduced in proportion to each other.
What two hemoglobins travel together in an electrophoresis?
Hemoglobin A2
Hemoglobin E
How would an electroporesis of an individual with beta-hemoglobin major appear?
No Hemoglobin A1 band
Some Hemoglobin A2 band
Some Hemoglobin F band
How would an electroporesis of an individual with HbEB0 appear?
No Hemoglobin A1
More Hemoglobin A2 than beta-thalassemia major (because HgE travel in the same band as Hemoglobin A1)
More Hemoglobin F band than beta-thalassemia major
Why is it important to not solely rely on electroporesis to diagnose iron deficiency anemia?
Because if a patient has beta thalassemia and is also iron deficient then there hemoglobin A2 should appear normal and beta thalassemia could be missed.
What would you find on the peripheral smear of a patient with thalassemia/
- Target cells
- Microcytosis
- Polychromasia
- Mild anisocytosis
What would the chemistry profile of a patient with thalassemia look like?
Increased:
- total/indirect bilirubin
- lactate dehydrogenase (LDH)
- Aspartate aminotransferase (AST)
*all of which are related to lysed RBC
Untreated thalassemia patients can often result in skeletal deformities, including frontal bossing. What is this caused by?
Expanded bone marrow
Untreated thalassemia patients can get enlarged livers, why?
Extramedullary hematopoiesis
Why would a patient with thalassemia be at risk for heart, liver and pituitary dysfunction or failure?
Thalassemia —>Increased iron absorption
Transfusion —> Iron overload
Excess iron will accumulate in the heart, liver and pituitary
Patients with untreated thalassemia can often present with short statue and delayed-onset of puberty. Why?
Ineffective erythropoiesis and endocrinopathies will delay growth and development
What type of thalassemia is characteristic of endocrinopathies?
Cooley’s anemia aka Beta-thalassemia major
Chronic hemolytic anemia patients are also at risk for what lung related issue?
Pulmonary hypertension
What prevents significant cardiac dysfunction development in thalassmenia patients receiving frequent transfusions?
Chelation therapy
What is the most common chelation therapy used for transfusion patients?
Deferoxamine- infused subcutaneously over 8-12 hours usually in the abdominal area 5-7 times a week.
What chelation therapy would you use if you lived in Europe?
Deferiprone- oral used with deferoxamine
What is an oral chelator that is just as effective as deferoxamine and is also available in the US?
Deferasirox (ICL670)
What could you prescribe a beta-thalassemia patient to increase increase the production of fetal hemoglobin?
- Hydroxyurea
- Butyrate
- Decitabine
Can you cure thalassemia?
Yeah with a bone marrow transplant
What can be given to a newborn who screened positive for thalassemia?
Prophylactic penicillin
