Hemaglobinopathies Flashcards
The ratio of alpha:beta chains in HbA is very important and should be?
1:1
An imbalance results in unstable alpha- or beta-globin chains, which then results in disease
Which test is more infomraitive regarding a diagnosis of hemaglobinopathies: hemoglobin electropheresis or isoelectric focusing gel?
isoelectric focusing gel
Mutations in what gene cause Beta-Chain Hemaglobinopathies?
HBB
This is the single gene responsible for the formation of beta-globin chains
Beta-thalassemia is caused by ____ inheritance of two pathogenic variants
bi-allelic
Sickle cell is caused by ________ inheritence of specific mutaiton.
homozygous
Beta-Thal Major “Cooley’s Anemia)
- absent beta-globin subunit production (BETA-NULL mutation)
- no fetal onset because fetus has no beta chains
- most severe
- deadly without treatment
- risk of iron overload (so need chelation therapy whcih has lots of side effects)
- RBC transfusions
Beta-Thal Intermedia
- BETA-PLUS mutation
- less severe & more variable
- leg ulcers, distended abdomen, splenomegaly
- ## chelation therapy indicated (has lots of side effects)
Beta-thalassemia results in…
reduced number of normal beta-globin chains
What is th enumber one cause of hospitalizations for sickle cell patients?
Vaso-occlusion and pain crises
Hemaloglobinopathies often get stuck in a feedback loop of…
chronic severe oxidative stress
Severe vaso-occlusive events can result in…
sudden unexpected death
After a sickle-cell vaso-occlusive event, reprofusion allows cell aggregates to free themselves allowing for blodo flow to be restored. This flood blood and O2 leads to inflammation and cell damange. This can lead to organ failure.
Baso-occlusive ischemia-reprofusion events cause excrutiating pain.
Hydroxyurea is a treatment for sickle cell disease.
- Exhibits cytoxicity by stalling in S-phase of cell cycle- reduces platelet count, WBC
- Less cells = Less adhesion = Less formation of aggregate
- also increases HbF production which has gamma instead of beta sub-units
- drug effects every step of the disease process
Do most patients with sickle cell get stem cell therapy?
no and it’s not curative
What hematological testing shoudl be ordered for betca chain hemaglobinopathies?
- CBC and hemoglobin electropheresis
MCV will be low in = sickle cell or beta-thal
Acute Chest Syndrome in Sickle Cell
No 1 cause of death
No 2 cause of hospitalization
Beta-thalassemia trait carrier
a normal MCV would support this conclusion
What two genes are responsible for alpha-chain globins?
HBA1 and HBA2
- disease is mostly caused by deletions
What are hte two clinically significant forms of alpha thalassemia?
- Hemoglobin H (HbH) disease
- Hemoglobin Bart (Hb Bart) hydrops fetalis
Normal, Silent Carrier, Cis Carrier, Trans Carrier, HbH Disease, Hb Bart Hydrops Fetalis
Hemoglobin H Disease
- high variability
- splegnamegaly and jaundice
- low MCV and abnormal electropheresis
Carrier screening for alpha-thal is challenging.
can look for common deletions and rare variants
What are the potential reproductive risks?
- At risk for offspring with Hemaglobin H diseaase.
- Molecular testing needed
- If Asisn, more aggressive with screening becuase they are more likely to be cis carriers
What are the potential reporductive risks?
child could only be carrier at worst
Hemaglobin Bart (Hydrops Fetalis)
- severe anemia
- prenatal onset
- IUFD or neonatal death
What are the hematologic findings for Hemoglobin Bart (Hydrops Fetalis)?
- macrocytic anemia (high MCV)
- very abnormal hemoglobin electropheresis
What are the US findings for Hemoglobin Bart Hydroops Fetalis?
- increased NT
- hepatosplenomegaly
- placentomegaly
- hydrops
- elevated middle cerebral artery Doppler
- onset can range from late 1st trimester to early 3rd trimester
Do fetuses with Hemoglobin Bart Disease have HbF?
Nope. Just HbBart is all they have.
HB Bart (Hydrops Fetalis) is a lethal diagnosis.
- some facilities will give intrauterine transfusions
- these will be needed indefinitely
- not curative
- stem cell transplantation in the future. maybe?
