Thalassemias Flashcards
When does alpha chain production begin?
Immediately, as it is required for fetal survival
How long after birth does beta globin take over for gamma globin?
3-6 months
Where is the alpha chain gene located?
Chrom 16
Where is the beta chain gene located?
Chrom 11
What type of Hb is common in alpha-thal?
Hb H
Hb Barts
What type of Hb is common in beta-thal?
Increase F or A2
What chain is defected in thal major usually?
Beta
Where is beta-thal very common inthe world?
mediterranean
Why does thal lead to anemia?
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.
What are the three types of thal?
Major
Inmdt - 7-10g Hb that are normal
Minor - may have mild anemia
What are signs of a person with thal major?
Very active bm, mishappen limbs, improper teeth formation, abnormal facial features (flat nose), massive hepatosplenomegaly (due to hemolytic anemia). Excessive pigmentation of skin
How long do the RBCs live in thal?
30 days. So liver and spleen are enlarged bc it’s clearing wasted cell parts.
Why does thal lead to increased susceptibility to bacterial infxns?
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)
Why is there iron overload in thal?
- Transfusion iron
- Increased iron absorption (ineffective erythropoeisis, decreased hepcidin, increased absorption and release of iron from macrophages)
Why are people with thal hypercoagulable?
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
Why is thal associated with endocrine and bone disease?
Hypogonadism, pituitary insufficiency, osteopenia (bone marrow expansion, endocrine dysfunction, iron chelators)
What are the clinical presentations of thal so variable?
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.
What blood type is elevated in thal?
A2 Hb will be above 3.5%
What is different above the microscopic appearance of cells in thal?
microcytic, hypochromatic, anisocytosis, poikilocytosis, (all like fe deficiency). also, increased basophilic staining because rapid abnormal blood production. Not exclusive to thal.
Where do we see basophilic stippling?
Thal hemolytic anemia myelodysplastic syndrome/sideroblastic anemia megalobastic anemia heavy metal poisoning
What are the most common diagnosis methods of thal?
HPLC or Electrophoresis. These cannot be used for alpha-thal however, which requires pcr
What is hereditary persisntece of fetal hb?
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.
What is E/Beta-thal?
One beta globin gene with a thal gene and one carrying hb E gene. SE asian popular. Considered intermediate.
What is hemoglobin lepore?
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.
What is alpha-thal?
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
Describe Hb H?
Very high oxygen affinity, like CO. Some increased epo but no as extreme as beta-thal.
What is Hb Constant Spring?
mRNA copies another 31 AAs, making unstable mRNA, leading to marked decraese in translation of alpha gene.
