Lecture 13 Chapter 25 Flashcards
What is the difference/similarity between hemoglobinopathies and thalassemias
Similarity: globulin chains are effected
Difference: hemoglobinopathies = single point mutation
Thalassemias = deletion of genes (genes are being deleted or are not being expressed)
How do people with thalassemia have different severities?
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
What is the cause of a-thalassemia and when does it occur
Unable to make the alpha chain
Problems show up in utero
What is the cause of b-thalassemia and when does it occur
Unable to make beta chain
Problems occur 6 - 12 months after birth
What are thalassemias?
An imbalance in the globulin chains
What happens when there is a globulin chain imbalance
Causes globulin chains to precipitate. Macrophages do not like any type of precipitation, so they remove the imbalanced globulin chains, causing anemia
What are the two b-thalassemia genes
B-thalassemia minor
B-thalassemia major (100x worse than minor)
What are the 4 a-thalassemia genes
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
What kinds of cells are seen in thalassemias
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)
What types of cells are seen with thalassemias
Microcytic, hypochronic
RBC inclusions
Basophilic stippling
What controls the expression of the gene but is not part of the gene
Enhancers and promoters
Name the types of mutation
What is the main cause of thalassemias
Deletion
What are the 4 syndromes of b-thalassemia and their characteristics
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
What is the reticulocyte count in a thalassemic patient?
It would be elevated if you don’t correct for anemia. If corrected, count would be normal
What happens to those born with B-thalassemia major?
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
What does this hair-like image on the skull indicate?
The medullary cavity in the bone marrow is expanding in order to accommodate making more cells
What kind of hematopoiesis is thalassemia
Ineffective
How can you determine the size of a RBC next to a small lymphocyte
Small lymphocyte’s nucleus are typically 7-9 nm and RBCs are typically 6-8 nm
What will the blood smear look like for b-thalassemia major
+4 target cells
+4 poikilocytosis (elliptocytes, schistocytes, tear drops, spherocytes)
+4 anisocytosis
nRBCs
Hypochromic, microcytic
Basophilic stippling, HJ bodies, pappenheimer bodies
What is the status of iron and ferritin in those with thalassemia
Iron will be normal, gets recycled after cell is destroyed
Ferritin could be elevated
What is megaloblastic crisis
Can happen to those with thalassemia that are making a lot of RBCs and run out of folate
What is the genotype and no. of genes present normally for alpha
aa/aa
4 genes
What is the genotype and no. of genes present for a silent carrier
aa/-a
3 genes
What is the genotype and no. of genes present for the a-thalassemia trait
-a/-a or aa/- -
2 genes
What is the genotype and no. of genes present for Hgb H
-a/- -
1 gene
What is the genotype and no. of genes present for Hgb Barts / hydrops fetalis
- -/- -
0 genes
What develops when you have Hgb H
Beta tetromeres that last 15 days because there is not enough alpha
A patient has a problem in utero with creating alpha, what happens to the hgb?
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
Label the a-thalassemias
What disease and stain
Hemoglobin H
Supravital stain
Disease and blood smear type
Mother with hemoglobin H
Severe anemia, poikilocytois, microcytic, hypochromic
Disease and blood smear type
Still born fetus with hemoglobin Bart’s
Anisocytosis, Hgb H, RBC inclusions
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)
The child will have a more severe sickle cell anemia since they do not have one normal B gene
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
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)
What is the result if someone has b-thalassemia and Hgb C - thalassemia
Severe anemia
What is the result if someone has a-thalassemia and Hgb C - thalassemia
Symptoms are lessened
What is the result if someone has Hgb E and Hgb S
Symptoms: very severe anemia
What is the result if someone has b-thalassemia and Hgb E - thalassemia (Be/B0)
Presents itself as homozygous E
What is the result if someone has a-thalassemia and Hgb E - thalassemia
Symptoms = less
Name the disease based on the gel electrophoresis results
What is osmotic fragility
Trying to find out now easily we can make a RBC lyse/break apart
What are some ways to test between IDA and thalassemia
- Ferritin levels: IDA = low, thalassemia = elevated (however cannot rely on results b/c ferritin is an acute phase reactant)
- Free erythrocyte protoporphyrin (FEP) or lead and zinc protoporphyrin (ZnPP) levels: IDA = goes up cause no iron, thalassemia = normal
- RBC count: thalassemia = increase, IDA = decline
- Mentzer index = MCV/RBC count (<13 = thalassemia; >13 = IDA)
