Heme/onc Lec 7 - Thalassemia

Front 1

what is HbA made of?

Back 1

- 2 alpha, 2 beta chains

Front 2

what are the characteristics of the alpha & beta globin cluster?

Back 2

- alpha: chromosome 16, duplicate genes, homologous

- beta: chromosome 11, one gene

Front 3

what are the Hb genes expressed in gestation & first 6 months of life? what is Hb A2?

Back 3

- Hb F sustains fetus (alpha + gamma)

- declines by 6 months

- Hb A2 = delta gene + alpha

Front 4

what happens in CO poisoning?

Back 4

- Hb curve shifts to the left & cannot unload O2 to tissues --> hypoxia

Front 5

what does sickle cell do to the Hb curve?

Back 5

- decreased O2 binding & O2 dissociation shifted to the right

Front 6

what is the difference between a hemoglobinopathy vs thalassemia?

Back 6

- hemoglobinopathy: structural or qualitative changes in Hb

- thalassemia: mutation that leads to decreased production

Front 7

what is beta thalassemia major (coopley's anemia)?

Back 7

- very severe anemia, transfusion dependent

- homozygous complete loss of beta globin gene expression

Front 8

what is beta thalassemia intermedia?

Back 8

- moderate anemia, not transfusion dependent

- mutations in both alleles but quantity produced of normal HbA is greater than that seen in beta thalassemia major

Front 9

what is beta thalassemia minor?

Back 9

- clinically mild or silent

- Mutation of single beta thalassemia allele

Front 10

what is hydrops fetalis (bart's syndrome)?

Back 10

- incompatible with life, 4 alpha globin chain mutations

Front 11

what is Hb H disease?

Back 11

- severe phenotype

- deletion of 3 alpha genes

Front 12

what is alpha thalassemia minor? what is homo vs heterozygous?

Back 12

- deletion of 2 alpha genes

- homozygous: on same chromosome (aa/--)

- heterozygous: on alternate chromosomes (a-/a-)

Front 13

what is alpha thalassemia trait?

Back 13

- individuals have no anemia

- deletion of 1 alpha globin gene (a-/aa)

Front 14

what is the difference b/w a deletion & non-deletion mutation for alpha thalassemia?

Back 14

- deletion is more common and actually deletes part of gene

- non-deletion is point mutations that inactivate genes

Front 15

what is Hb Constant Spring?

Back 15

- substitution of alpha2 termination codon --> leads to non-functional protein -> elongated unstable chain

- also a variant hemoglobinopathy b/c elongated protein chain produced in addition to decreased synthesis

Front 16

what is the pathophysiology of alpha thalassemia?

Back 16

- beta chain excess --> beta tetramers precipitate (Hb H) --> damage & hemolysis

Front 17

what is the major difference genetically b/w alpha & beta thalassemias?

Back 17

- beta have point mutations rather than deletions

Front 18

what do the excess alpha chains bind to in beta thalassemia?

Back 18

- can bind to gamma = Hb F increased in adults

- can bind to delta = Hb A2 increased in adults

- can bind to itself

Front 19

why do beta thalassemias start having problems early in life?

Back 19

- b/c alpha is precipitating in the BM leading to destruction of RBCs & ineffective erythropoiesis

Front 20

why do you have to do iron chelation in beta thalassemias?

Back 20

- b/c giving them so much blood via transfusion

Front 21

what is HbE?

Back 21

- a combined hemoglobinopathy & thalassemia

- mutation in mRNA splice site --> reduced synthesis of b-E chain & thalassemia phenotype

- abnormal b chain

Front 22

what does the CBC look like in thalassemias?

Back 22

- low Hb & Hct

- low MCV or microcytosis = requirement

- high red cell count (should be 3x Hb, but way higher than this in thalassemia)

Front 23

what do you see on peripheral blood smear in thalassemias? how do you differentiate it from iron deficiency?

Back 23

- see small red cells, hemolytic anemia (polychromasia, basophilic stippling, elevated reticulocyte count)

- poikilocytosis (variable cell shape)

- red cell fragments & target cells

- iron studies NORMAL!

Front 24

what is basophillic stippling and where do you see it?

Back 24

- accumulation of rRNA

- find in hemolytic anemia & Pb poisoning

Front 25

what do you see on electrophoresis for thalassemias? what can you see with alpha thalassemia? HbH? beta thalassemia?

Back 25

- NORMAL b/c there is not qualitative disorder only quantitative

- alpha = only see alpha

- HbH (3 alpha deleted) = fast migrating beta homotetramer

- beta thalassemia = see HbA2 & HbF increased

Front 26

what is HPLC? which thalassemia is it good for?

Back 26

- separates Hb based on hydrophobicity

- good for beta thalassemia b/c can separate out Hb A2 & HbF

Front 27

what types of thalassemias do you generally use PCR sequencing for?

Back 27

- alpha