Hemoglobinopathies

Question 1

Hemoglobinopathies

Sickle cell involves a mutation of which Hbg type and side chain?

Answer 1

Hgb A, beta chain (glutamic acid -> valine)

Question 2

Hemoglobinopathies

How common is sickle cell trait?

Answer 2

1/12 African Americans

Question 3

Hemoglobinopathies

Aside from African Americans, who is at risk for carrying the sickle cell mutation? (ethnicity-wise)

Answer 3

Those from Greece, Italy, the Middle East, and East India

Question 5

Hemoglobinopathies

What triggers RBCs to sickle in affected individuals?

Answer 5

Low O2 states

Question 6

Hemoglobinopathies

Why are sickle cells bad - how do they cause harm?

Answer 6

Vasoocclusion of organs/tissues

Question 7

Hemoglobinopathies

How does acute chest syndrome present?

Answer 7

Pulmonary infiltrates on CXR
Fever, hypoxia, acidosis
No infection

Question 8

Hemoglobinopathies

What is the typical electrophoresis in sickle cell disease and trait?

Answer 8

SS: Mostly Hgb S, some A2 and F
Trait: Mostly Hgb A noted, with some S, A2, and F

Question 9

Hemoglobinopathies

Who should be offered sickle cell carrier screening?

Answer 9

Those of African and mediterranean ancestry

Question 10

Hemoglobinopathies

How should you screen for sickle cell in those with African or other heritage?

Answer 10

African-American: CBC + electrophoresis

Other: CBC with diff, and electrophoresis only if microcytic (<80)

Question 11

Hemoglobinopathies

What are the risks associated with sickle cell disease in pregnancy?

Answer 11

PTL, PPROM, infection post-partum, IUGR, IUFD

Question 12

Hemoglobinopathies

How much folic acid should patients with sickle cell take daily?

Answer 12

4mg/day

Question 13

Hemoglobinopathies

How do you counsel patients with sickle cell on crisis avoidance?

Answer 13

Avoid triggers (cold, physical exertion, dehydration, and stress)

Question 14

Hemoglobinopathies

Can hydroxyurea be used in pregnancy to avoid a sickle crisis?

Answer 14

No - hydroxyurea is teratogenic

Question 15

Hemoglobinopathies

How do we treat sickle crises?

Answer 15

O2, opiods
Evaluation/treatment of cause (infection, dehydration)
Management of compliations (acute chest)

Question 16

Hemoglobinopathies

When exchange transfusions are utilized in pregnancy for sickle cell, what is the typical indication?

Answer 16

Reduce frequency of pain crises

Question 17

Hemoglobinopathies

With an exchange transfusion, what is the treatment goal for % HgbS?

Answer 17

Hgb S <40%

Question 18

Hemoglobinopathies

How should we monitor fetuses in pregnancies complicated by SS?

Answer 18

Serial growth ultrasound q 4-6 weeks

Antepartum testing beginning at 32 weeks

Question 19

Hemoglobinopathies

What electrophoresis pattern is consistent with beta-thalassemia?

Answer 19

Increased Hgb A2 > 3.5%, increased Hgb F, no Hgb S

Question 20

Hemoglobinopathies

What causes B-thal?

Answer 20

Bad beta-chain -> loss of type A Hgb (alpha/beta)

Question 21

Hemoglobinopathies

What are the two general types of gene mutations associated with B-thal?

Answer 21

B (0) - absent beta chain production

B (+) - decreased amount of beta chain production

Question 22

Hemoglobinopathies

What are the two grades of B-thal severity?

Answer 22

B-thal MINOR: mild anemia

B-thal MAJOR: severe anemia, complications

Question 23

Hemoglobinopathies

What complications are associated with B-thal major over a lifetime (outside of pregnancy)

Answer 23

Extramedullary hematopoeisis
Delayed sexual development (due to hemosiderin deposition in hypothalamus)
Poor growth
Death by age 10 if blood transfusions are not initiated

Question 24

Hemoglobinopathies

What patients with B-thal major are candidates for pregnancy?

Answer 24

Normal heart function

No end organ damage from chronic transfusion (or h/o transfusion, coupled with deferoxamine for chelation)

Question 25

Hemoglobinopathies

Which ethnicities are most commonly associated with B-thal mutations?

Answer 25

Mediterranean, Asian, middle eastern, Hispanic, W.Indian

Question 26

# Hemoglobinopathies What is the outcome of B-thal combined with HgbS?

Answer 26

Severe anemia due to absent functional beta-chain production -> no Hgb A production

Question 27

# Hemoglobinopathies While pregnancies with B-thal minor are usually favorable, what outcomes should be monitored for?

Answer 27

IUGR, oligohydramnios

Question 28

# Hemoglobinopathies Instead of iron, what supplement should be given to women with B-thal?

Answer 28

Folic acid 1mg/day

Question 29

# Hemoglobinopathies If you diagnose a patient with B-thal, what supplement should be initiated, and who else should be tested?

Answer 29

Initiated folic acid 1mg/day Test father with CBC -> electrophoresis if microcytic Genetic counseling if dad also a carrier

Question 30

# Hemoglobinopathies When should you refer a patient for alpha-thal testing?

Answer 30

Microcytic anemia Normal electrophoresis and iron testing SE Asian, African, W Indian, and mediterranean

Question 31

# Hemoglobinopathies What causese alpha-thalassemia?

Answer 31

Defunct alpha-chain production -> decreased Hgb A (alpha/beta), A2 (alpha/delta), and F (alpha/gamma)

Question 32

# Hemoglobinopathies Alpha thall involves mutations in how many alpha genes? What are the possible mutation combinations called?

Answer 32

TRANS: a_/a_ CIS: __/aa

Question 33

# Hemoglobinopathies What ethnicities are most likely to be affected by sickle cell?

Answer 33

SE Asian, African, W. Indian, Mediterranean

Question 34

# Hemoglobinopathies Why are E.Asian individuals with a-thall more likely to have a child with Hgb Barts than African individuals?

Answer 34

CIS mutation (__/aa) seen more commonly in SE Asia -> more likely to have fetus with (__/__)

Question 35

# Hemoglobinopathies What is the outcome of Hgb Barts?

Answer 35

Fetal hydrops, IUFD, preeclampsia

Question 36

# Hemoglobinopathies Does a-thal worsen or improve sickle cell?

Answer 36

A-thal improves presentation of sickle cell, as less Hgb S (alpha/sickle) can be produced!)