Hemaglobinopathies

Question 1

The ratio of alpha:beta chains in HbA is very important and should be?

Answer 1

1:1

An imbalance results in unstable alpha- or beta-globin chains, which then results in disease

Question 2

Which test is more infomraitive regarding a diagnosis of hemaglobinopathies: hemoglobin electropheresis or isoelectric focusing gel?

Answer 2

isoelectric focusing gel

Question 3

Mutations in what gene cause Beta-Chain Hemaglobinopathies?

Answer 3

HBB
This is the single gene responsible for the formation of beta-globin chains

Question 4

Beta-thalassemia is caused by ____ inheritance of two pathogenic variants

Answer 4

bi-allelic

Question 5

Sickle cell is caused by ________ inheritence of specific mutaiton.

Answer 5

homozygous

Question 6

Beta-Thal Major “Cooley’s Anemia)

Answer 6

• 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

Question 7

Beta-Thal Intermedia

Answer 7

• BETA-PLUS mutation
• less severe & more variable
• leg ulcers, distended abdomen, splenomegaly
• ## chelation therapy indicated (has lots of side effects)

Question 8

Beta-thalassemia results in…

Answer 8

reduced number of normal beta-globin chains

Question 9

What is th enumber one cause of hospitalizations for sickle cell patients?

Answer 9

Vaso-occlusion and pain crises

Question 10

Hemaloglobinopathies often get stuck in a feedback loop of…

Answer 10

chronic severe oxidative stress

Question 11

Severe vaso-occlusive events can result in…

Answer 11

sudden unexpected death

Question 12

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.

Answer 12

Baso-occlusive ischemia-reprofusion events cause excrutiating pain.

Question 13

Hydroxyurea is a treatment for sickle cell disease.

Answer 13

• 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

Question 14

Do most patients with sickle cell get stem cell therapy?

Answer 14

no and it’s not curative

Question 15

What hematological testing shoudl be ordered for betca chain hemaglobinopathies?

Answer 15

• CBC and hemoglobin electropheresis

MCV will be low in = sickle cell or beta-thal

Question 16

Acute Chest Syndrome in Sickle Cell

Answer 16

No 1 cause of death
No 2 cause of hospitalization

Question 17

Answer 17

Beta-thalassemia trait carrier
a normal MCV would support this conclusion

Question 18

What two genes are responsible for alpha-chain globins?

Answer 18

HBA1 and HBA2
- disease is mostly caused by deletions

Question 19

What are hte two clinically significant forms of alpha thalassemia?

Answer 19

• Hemoglobin H (HbH) disease
• Hemoglobin Bart (Hb Bart) hydrops fetalis

Question 20

Normal, Silent Carrier, Cis Carrier, Trans Carrier, HbH Disease, Hb Bart Hydrops Fetalis

Answer 20

Question 21

Hemoglobin H Disease

Answer 21

• high variability
• splegnamegaly and jaundice
• low MCV and abnormal electropheresis

Question 22

Carrier screening for alpha-thal is challenging.

Answer 22

can look for common deletions and rare variants

Question 23

What are the potential reproductive risks?

Answer 23

• 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

Question 24

What are the potential reporductive risks?

Answer 24

child could only be carrier at worst

Question 25

Hemaglobin Bart (Hydrops Fetalis)

Answer 25

• severe anemia
• prenatal onset
• IUFD or neonatal death

Question 26

What are the hematologic findings for Hemoglobin Bart (Hydrops Fetalis)?

Answer 26

• macrocytic anemia (high MCV)
• very abnormal hemoglobin electropheresis

Question 27

What are the US findings for Hemoglobin Bart Hydroops Fetalis?

Answer 27

• increased NT
• hepatosplenomegaly
• placentomegaly
• hydrops
• elevated middle cerebral artery Doppler
• onset can range from late 1st trimester to early 3rd trimester

Question 28

Do fetuses with Hemoglobin Bart Disease have HbF?

Answer 28

Nope. Just HbBart is all they have.

Question 29

HB Bart (Hydrops Fetalis) is a lethal diagnosis.

Answer 29

• some facilities will give intrauterine transfusions
• these will be needed indefinitely
• not curative
• stem cell transplantation in the future. maybe?