Disorders of Hemoglobin and Hemoglobin Electrophoresis

Question 1

Hgb has two alphas and two betas What chromosome has alpha and what chromosome has beta?

Answer 1

alpha = 16
beta = 11

Question 2

What two globin types are normally not transcribed after 8 weeks gestation?

Answer 2

zeta and epsilon (don’t bother remembering)

Question 3

What globin type is usually not transcribed after the first year of life?

Answer 3

gamma (make up fetal hemoglobin)

Question 4

How many pairs of alpha genes are on chromosome 16?

Answer 4

2 - which is a good thing

Question 5

Delta continues to be transcribed, but why is it not seen all that often?

Answer 5

it’s on chromsome 11, but beta is transcribed much more efficiently

Question 6

What are the most electrochemically favorable tetramer for hemoglobin?

Answer 6

two alphas and two betas (or beta-like)

this one is Major Adult Hgb A

Question 7

What is the tetramer for Hgb A2 (minor adult)?

Answer 7

two alphas and two deltas

Question 8

How do we identify and quantitate hemoglobinopathies?

Answer 8

hgb electrophoresis

or

high pressure liquid chromatography

Question 9

IN general terms, what is a thalassemia?

Answer 9

inherited disorder where there is impaired or absent TRANSCRIPTION of one or more globin genes (the genes themselves are normal)

Question 10

If you have an alpha globin gene knocked out, what kind of hemogobin will you end up with during fetal life?

Answer 10

you’ll get more hemoglobin barts (4 gammas)

which will show up on the newborn screen!

Question 11

If you have an alpha globin gene knocked out, how long during life will you continue to have alpha barts?

Answer 11

once the beta globins start going, you will stop getting barts within a week of birth!

so adults will never have barts on an electrophoresis even if they do have an alpha gene knocked out.

Question 12

So once you get to adulthood, what is the only way you can diagnosed a lack of one alpha globin gene?

Answer 12

genetic testing

much more expensive than the newborn screen, so that’s why the newborn screen is helpful

Question 13

Does lacking one alpha gene affect you symptomatically?

Answer 13

nope. not at all. you don’t even get anemic. But it’s helpful to know for genetic counseling purposes

Question 14

If you have two alpha genes missing, what do you have?

Answer 14

alpha thalassemia minor

Question 15

Do you get symptoms if you are missing two alpha genes?

Answer 15

not really, because you still have two active alpha genes that will pair with betas just fine

Question 16

What is their normal CBC with alpha thalassemia minor?

Answer 16

they have a little higher epo, so higher RBC, higher RDW and life-long low MCV

NO anemia

Question 17

Do you still get barts on newborn screen with alpha thalassemia minor?

Answer 17

yes

Question 18

What if you’re missing three alpha genes? What type of hemoglobin will you get now?

Answer 18

you’ll have so much extra beta, you’ll end up with beta tetramers (Hgb H)

Question 19

What disease is this?

Answer 19

alpha thalassemia major (or hemoglobin H disease)

Question 20

What symptoms do you get with alpha thalassemia major?

Answer 20

lifelong severe hemolytic anemia

Question 21

Ethnically, how do the cis and trans alpha thalassemia minor differ?

Answer 21

asians get cis and africans get trans

mostly just important for genetic counseling. symptom and testing-wise htey don’t differ

Question 22

What happens with four alpha genes deleted?

Answer 22

hydrops fetalis

Question 23

If there is hgb barts on the screen, but normal hgb and normal MCV, what’s the answer?

Answer 23

single alpha gene deletion

Question 24

If there is hgb barts, anemia and low MCV, what is it

Answer 24

alpha thal major

Question 25

If there is hgb barts, low mCV and normal or only slightly low hgb, what is it?

Answer 25

alpha thal minor

Question 26

How long would you need to wait for a hgb electrophoresis to be accurate after a red cell transfusion?

Answer 26

3 months (how long RBCs stick around for)

Question 27

Deletion or decreased transcription of beta gene results in proporionate increase in what globin?

Answer 27

delta, so you get more hemoglobin A2

Question 28

People with a single beta gene deleted have what disease?

Answer 28

beta thal trait

Question 29

What will beta thal trait look like on CBC?

Answer 29

microcytic slight anemia with increased RBC and increased RDW

Question 30

What will beta thal trait look like on a newborn screen?

Answer 30

Normal!! Because they’re still using Hgb F, which doesn’t require beta globin

Question 31

After 6 months- 1 yr of life, how can you diagnose this using ELP?

Answer 31

elevated Hgb A2 and maybe elevated Hgb F (sometimes can have persistent expression of gamma)

Question 32

What other process can MASK thalassemia trait?

Answer 32

anything that lowers the Hgb A2, such as iron deficiency

Question 33

What’s the difference between beta-plus and beta-zero thal?

Answer 33

beta-zero is absence of the gene or complete failure to transcribe it

beta-plus is impaired or diminished transcription

not on test

Question 34

If they don’t have beta genes, what disease do they have?

Answer 34

Beta thalassemia major

Question 35

Can beta thal major make any Hgb A?

Answer 35

nope - only Hgb A2

Question 36

What’s the clinical result of beta thal major?

Answer 36

microcytic anemia for life, severe

should be followed by a clinical hematologist (all F, no A, get a consult right away)

Question 37

What is a hemoglobinopathy?

Answer 37

mutation in a globin gene that results in production of mutant globin protein which forms an abnormal tetramer

Question 38

Are mutations more common in beta or alpha?

Answer 38

beta mutations are much more common

Question 39

What are the three common hemoglobinopathies?

Answer 39

Beta-s
Beta-c
Beta-E

Question 40

What hemoglobinopathy is most common in minnesota?

Answer 40

beta-E because of the SE asian population. (20% of Hmong will have the trait!)

Beta C and S ar emore common in Africans

Question 41

What’s the tetramer for Hgb S?

Answer 41

aaBsBs

Question 42

What’s the tetramer for Hgb C?

Answer 42

aaBcBc

Question 43

What is the tetramer for Hgb E?

Answer 43

aaBeBe

Question 44

How do you diagnosed sickling diseases?

Answer 44

identify sickled RBCs on a smear

then confirm hemoglobin S

Question 45

What are the options to confirm the Hgb S?

Answer 45

precipitation tests
Latex bead immunoassay (hemocard)
Hgb ELP, cap electrophoresis or HPLC

Question 46

How do you diagnosed a sickle crisis on lab?

Answer 46

Trick question - there is no lab test. It’s a clinical diagnosis.

obviously check CBC w/ diff and do a blood smear with Hgb electrophoresis in a patient who doesn’t already have the diagnosis