Disorders of Hemoglobin and Hemoglobin Electrophoresis Flashcards
Hgb has two alphas and two betas What chromosome has alpha and what chromosome has beta?
alpha = 16 beta = 11
What two globin types are normally not transcribed after 8 weeks gestation?
zeta and epsilon (don’t bother remembering)
What globin type is usually not transcribed after the first year of life?
gamma (make up fetal hemoglobin)
How many pairs of alpha genes are on chromosome 16?
2 - which is a good thing
Delta continues to be transcribed, but why is it not seen all that often?
it’s on chromsome 11, but beta is transcribed much more efficiently
What are the most electrochemically favorable tetramer for hemoglobin?
two alphas and two betas (or beta-like)
this one is Major Adult Hgb A
What is the tetramer for Hgb A2 (minor adult)?
two alphas and two deltas
How do we identify and quantitate hemoglobinopathies?
hgb electrophoresis
or
high pressure liquid chromatography
IN general terms, what is a thalassemia?
inherited disorder where there is impaired or absent TRANSCRIPTION of one or more globin genes (the genes themselves are normal)
If you have an alpha globin gene knocked out, what kind of hemogobin will you end up with during fetal life?
you’ll get more hemoglobin barts (4 gammas)
which will show up on the newborn screen!
If you have an alpha globin gene knocked out, how long during life will you continue to have alpha barts?
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.
So once you get to adulthood, what is the only way you can diagnosed a lack of one alpha globin gene?
genetic testing
much more expensive than the newborn screen, so that’s why the newborn screen is helpful
Does lacking one alpha gene affect you symptomatically?
nope. not at all. you don’t even get anemic. But it’s helpful to know for genetic counseling purposes
If you have two alpha genes missing, what do you have?
alpha thalassemia minor
Do you get symptoms if you are missing two alpha genes?
not really, because you still have two active alpha genes that will pair with betas just fine
What is their normal CBC with alpha thalassemia minor?
they have a little higher epo, so higher RBC, higher RDW and life-long low MCV
NO anemia
Do you still get barts on newborn screen with alpha thalassemia minor?
yes
What if you’re missing three alpha genes? What type of hemoglobin will you get now?
you’ll have so much extra beta, you’ll end up with beta tetramers (Hgb H)
What disease is this?
alpha thalassemia major (or hemoglobin H disease)
What symptoms do you get with alpha thalassemia major?
lifelong severe hemolytic anemia
Ethnically, how do the cis and trans alpha thalassemia minor differ?
asians get cis and africans get trans
mostly just important for genetic counseling. symptom and testing-wise htey don’t differ
What happens with four alpha genes deleted?
hydrops fetalis
If there is hgb barts on the screen, but normal hgb and normal MCV, what’s the answer?
single alpha gene deletion
If there is hgb barts, anemia and low MCV, what is it
alpha thal major
If there is hgb barts, low mCV and normal or only slightly low hgb, what is it?
alpha thal minor
How long would you need to wait for a hgb electrophoresis to be accurate after a red cell transfusion?
3 months (how long RBCs stick around for)
Deletion or decreased transcription of beta gene results in proporionate increase in what globin?
delta, so you get more hemoglobin A2
People with a single beta gene deleted have what disease?
beta thal trait
What will beta thal trait look like on CBC?
microcytic slight anemia with increased RBC and increased RDW
What will beta thal trait look like on a newborn screen?
Normal!! Because they’re still using Hgb F, which doesn’t require beta globin
After 6 months- 1 yr of life, how can you diagnose this using ELP?
elevated Hgb A2 and maybe elevated Hgb F (sometimes can have persistent expression of gamma)
What other process can MASK thalassemia trait?
anything that lowers the Hgb A2, such as iron deficiency
What’s the difference between beta-plus and beta-zero thal?
beta-zero is absence of the gene or complete failure to transcribe it
beta-plus is impaired or diminished transcription
not on test
If they don’t have beta genes, what disease do they have?
Beta thalassemia major
Can beta thal major make any Hgb A?
nope - only Hgb A2
What’s the clinical result of beta thal major?
microcytic anemia for life, severe
should be followed by a clinical hematologist (all F, no A, get a consult right away)
What is a hemoglobinopathy?
mutation in a globin gene that results in production of mutant globin protein which forms an abnormal tetramer
Are mutations more common in beta or alpha?
beta mutations are much more common
What are the three common hemoglobinopathies?
Beta-s
Beta-c
Beta-E
What hemoglobinopathy is most common in minnesota?
beta-E because of the SE asian population. (20% of Hmong will have the trait!)
Beta C and S ar emore common in Africans
What’s the tetramer for Hgb S?
aaBsBs
What’s the tetramer for Hgb C?
aaBcBc
What is the tetramer for Hgb E?
aaBeBe
How do you diagnosed sickling diseases?
identify sickled RBCs on a smear
then confirm hemoglobin S
What are the options to confirm the Hgb S?
precipitation tests
Latex bead immunoassay (hemocard)
Hgb ELP, cap electrophoresis or HPLC
How do you diagnosed a sickle crisis on lab?
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
