Thalassemias Flashcards
(35 cards)
How many Hb alpha genes are there and how many Hb beta genes are there?
alpha-4
beta-2
Hb gamma is the fetal hemoglobin chain. a2y2 is fetal Hb. What is special about fetal Hb?
It does not give up oxygen as readily
Where are the alpha Hb genes located in the genome? The other Hb genes?
Alpha is on chromosome 16, the others are all on chromosome 11
How can you get iron overload with Beta-thalassemia?
Transfusions. RBCs get stuck in microcirculation/die so the body says make more RBCs. These die too and transfusions are needed. However, the transfusions can cause iron overload bc even though the RBCs die, the iron in the heme is continually recycled.
What is thalassemia MAJOR?
Beta-thalassemias
What are some clinical presentations of Beta-thalassemia?
Severe osteoporosis, malformed bones, flattened nose, boxed forehead, VERY LARGE SPLEEN due to hemolytic anemia (filled with dead RBC material), ankle ulcers
In general, why do we get iron overload? (big picture)
We do not have a mechanism to eliminate it from our bodies
Why do patients with thalassemias get iron overload?
Decreased Hepcidin bc the body senses dead RBCs and tells itself we need to make “new iron”
Why are patients with Beta-thalassemias in a hypercoaguable state?
Phosphatidylserine is exposed on the outside of the cell due to membrane damage and this is a recognition site for cell removal during apoptosis + it increases thrombin production (increased platelet activation)
What are the two types of Beta-thalassemias?
B^0 (no beta chains)
B^+(very few beta chains)
If A2 (meaning alpha2/delta2) levels are above 3.5%, what is this an indicator of?
Beta-thalassemia
What is a histological feature of RBCs that can help make a dx of B-thalassemia?
Target cells
What is a histiological feature of all hemolytic anemias?
Basophilic stippling
What are the main prognostic indicators of a transplant failure in pts with Beta-thalassemia?
Portal fibrosis, Hepatomegaly, Inadequate chelation
What is HPFH? (Hereditary Persistence of Fetal Hemogloblin)
Decrease in beta globin synthesis compensated by an increase in gamma chain synthesis. Could be co-deletion of delta/beta genes. Produces a favorable sickle syndrome.
What is Hemoglobin E disease?
A point mutation on the Beta globin gene (26 Glu to Lys) that presents w/ Beta-thalassemia minor in heterozygotes
What is Hemoglobin Lepore?
A delta/beta fusion chain which leads to diminished non-alpha chains (85-95% reduction) leading to thal-intermedia in heterozygotes and thal-major in homozygotes
Normal alpha chains present
How do you make a dx of Hemoglobin S/Beta-thalassemia?
HPLC- tells you what chains are present
Check out chart on page 97 of hematology book. Should see an increased A2 band, S band, increased F band
If you lose 4 alpha globin genes what happens?
You’re dead (you have Barts Hb which is gamma4). Also known as hydrops fetalis.
What is HbH disease?
Alpha-thalassemia where 3 alpha globin genes are mutated. This is less severe than Beta-thal major and affects older RBCs.
Where do you find cells that look like “golf balls”?
Tiger Woods’s blood, or HbH disease (either is acceptable, I asked Chesney)
What is alpha0 trait?
Two knockouts on one chromosome
What is alpha1 trait?
Two knockouts, each on separate chromosomes
What is the Hemoglobin Spring Constant?
A base substitution on the terminal sequence of the alpha globin chain mRNA that adds 31 bases and makes the mRNA unstable decreasing its translation (less alpha chains). Presents as severe alpha-thalassemia in homozygotes.
