Thalassemia (complete) Flashcards
What is the normal structure of Hb?
Made of 2 alpha-globin chains and 2 beta/delta/gamma chains
Hba1: 2a/2b (95%)
Hba2: 2a/2delta (3.5%)
HbF: 2a/2gamma (2%)
Describe how the composition of globin chains in Hb changes during fetal development and after birth
Think of that token graph
Fetal: mainly alpha/gamma, a little alpha/beta
After birth: changes to primarily alpha/beta – a little alpha/delta develops
Describe thalassemia and explain its molecular basis
Definition: underproduction of Hb chains b/c of mutations in globin gene (poor/absent function)
Two common types:
1) alpha-thal
2) beta-thal
What are the consequences of thalassemia generally speaking?
1) Free excess chains binding to RBC membrane
2) Membrane oxidative injury
3) increase membrane rigidity
4) Decreased membrane stability
What is the genetic mutation for alpha-thal?
Absence of 1-4 of 4 genes that control alpha-globin production
Chromosome 16
OVERALL: Alpha-globin underproduced
What is the genetic mutation of beta-thal?
Point mutations that result in dysfunctional gene (either moderate or severe)
Chromosome 11
OVERALL: Beta-globin underproduced
What is thalassemia minor (beta-thal trait)?
Beta gene: 1 normal, 1 moderately abnormal
Anemia: none-mild
MCV: normal-low
Tranfusion dpdt: No
What is thalassemia intermedia?
Beta gene: 2 moderately abnormal
Anemia: Mild-moderate
MCV: Low
Tranfusion dpdt: Sometimes
What is thalassemia major (Cooley’s anemia)?
Beta gene: 2 severely abnormal
Anemia: Severe
MCV: Low
Tranfusion dpdt: Always
What is alpha-thal trait (silent carrier)?
Alpha gene: - a / a a
Anemia: None
MCV: Normal
Transfusion dpdt: No
What is alpha-thal trait (2-gene deletion)?
Alpha gene: - a / - a or - - / a a
Anemia: None - mild
MCV: Normal - low
Transfusion dpdt: No
What is HbH disease?
Alpha gene: - - / - a
Anemia: Moderate - severe
MCV: Low
Transfusion dpdt: Sometimes
What is hydrops fetalis?
Alpha gene: - - / - -
Incompatible w/ life
What are the clinical manifestations of a pt w/ thalassemia?
1) Chronic hemolytic anemia
2) Expand bone marrow and extramedullary hematopoiesis
3) Increase iron absorption
4) Delayed growth and development
5) Pulmonary HTN
What are the abnormalities found on a CBC of a pt w/ thalassemia?
- Increased reticulocyte count
- Low MCV
- Low MCHC
What are the abnormalities found in the chemistry profile of a pt w/ thalassemia?
- Increased bilirubin
- Increased LDH
- Increased AST
B/c of lysed cells
What abnormalities are seen in the peripheral blood smear of a pt w/ thalassemia?
- Microcytosis
- Target cells
- Polychromasia
- mild Anisocytosis
- Sombrero shaped RBCs
Describe chronic hemolytic anemia as it relates to thalassemia
- Fragile RBC has short half-life
- Destroyed in marrow or reduced in spleen
- Splenomegaly b/c of so many damaged RBCs
Describe expanded bone marrow and extramedullary hematopoiesis as it relates to thalassemia
- Bone marrow expands to try and produce enough RBC
- Fills w/ RBC precursors (but they are fragile, easily destroyed)
- Causes frontal bossing, osteopenia, hepatomegaly, splenomegaly
Describe increased iron absorption as it relates to thalassemia
- Iron comes from diet and transfusions (instead of only one)
- Leads to high iron burden/overload
Chelation required
Describe delayed growth and development as it relates to thalassemia
Short stature and delayed puberty
Caused by:
1) anemia
2) increased metabolism
3) endocrinopathies
Describe endocrinopathies as they relates to thalassemia
2/3 of pts w/ Cooley’s anemia have this
Pituitary gland affected —> hypogonadotrophic hypogonadism
Hypothyroidism in 40-60% of pts w/ B-thal major
Describe pulmonary HTN as it relates to thalassemia
chronic hemolytic anemia increases risk for hypertension
Describe geographic distribution of thalassemia.
Most common in SE Asia, Africa, Meditarranean
Heterozygotes protected from malaria
Why are SE Asians w/ a-thal more likely than Africans w/ a-thal to have a child w/ hydrops fetalis?
SE Asians genes: - - / a a
African genes: a - / a -
Think of mode of inheritance
What treatments are available for pts w/ thalassemia?
1) Transfusion support
2) Increase fetal Hb production
3) Bone marrow transplant
Describe transfusion support as a treatment for pts w/ thalassemia
- Used in severe thalassemia
- Start in first 2 yrs
- Maintain normal Hb levels
- Avoids bone marrow expansion and extramedullary hematopoiesis
Chelation used to prevent Fe overload
Describe increased fetal Hb production as a treatment for pts w/ thalassemia
Agents: Hydroxyurea, butyrate, decitabine
- Induce gamma chain formation for excess alpha chains to bind with
- Reduces negative impact on RBCs
Describe bone marrow transplantation as a treatment for pts w/ thalassemia
- Used to cure thalassemia
- Only 30% of pts have been matched w/ an eligible sibling
Which method is used to screen newborns for thalassemia?
Same process/purpose as sickle cell disease screening
Heel prick
