Hemoglobinopathies in Pregnancy

Question 1

Composition of hemoglobin A

Answer 1

Two alpha chains

Two beta chains

Question 2

Composition of hemoglobin F

When does this hemoglobin predominate in the fetus?

Answer 2

Two alpha chains
Two gamma chains

12-24 weeks

Question 3

Composition of hemoglobin A2

Answer 3

Two alpha chains

Two delta chains

Question 4

Gene location of alpha-globin

Answer 4

Short arm of chromosome 16

Question 5

Gene location of beta-globin

Answer 5

Short arm of chromosome 11

Question 6

Genetics of sickle cell disease

Answer 6

Autosomal recessive
Single nucleotide substitution in beta-globin gene (chromosome 11)
Causes abnormally-shaped hemoglobin (sickling)
Carriers = sickle cell trait

Question 7

Abnormal hemoglobin in sickle cell disease

Answer 7

Hemoglobin S

Question 8

Other sickle cell disorders

Answer 8

Hgb S + add’l abnormality of beta-globin structure or production
Can cause similar clinical manifestations as hgb SS
- Hemoglobin SC
- Hemoglobin S/beta-thal

Question 9

Epidemiology

Answer 9

1 in 12 African Americans has SCT
1 in 300 AA newborns has some form of SCD
1 in 600 AA newborns has SC anemia

Question 10

Pathophysiology of vasoocclusive crises

Answer 10

Distorted red cells lead to increased viscosity, hemolysis, and anemia; decrease in oxygenation
Sickling occurs in small vessels - can interrupt blood supply to vital organs
Repeated vasoocclusive crises lead to widespread microvascular obstruction, with interruption of normal perfusion/function of several organs (spleen, lungs, kidneys, heart, brain)

Question 11

Splenic function in SCD

Answer 11

Microvascular obstruction leads to autosplenectomy by adolescence - patients are functionally asplenic
Leads to increased incidence and severity of infection

Question 12

Most significant threat to sickle cell patients

Answer 12

Acute chest syndrome

Question 13

Acute chest syndrome

Answer 13

Fever with pulmonary infiltrate
- Infiltrates due to vasoocclusion from sickling or embolization of marrow from long bones affected by sickling
- Not infectious
Hypoxemia and acidosis

Question 14

Diagnosis of hemoglobinopathies

Answer 14

Hemoglobin electrophoresis (in African populations)
Start with CBC for others

Question 15

Genetics of alpha-thalassemia

Answer 15

Deletion of 2 or more copies of the 4 alpha-globin genes

2 genes = alpha-thal trait/minor (carrier), mild anemia
3 or 4 genes = alpha-thal major

a-/aa = asymptomatic
a-/a- or aa/– = mild anemia
a-/– = hemoglobin H disease, hemolytic anemia
–/– = hemoglobin Bart’s disease, hydrops fetalis

Question 16

Genetics of beta-thalassemia

Answer 16

Mutation in beta-globin gene
Deficient or absent beta-chain production, leading to absence of Hb A
Carriers = beta-thal minor

Question 17

Beta-thal major

Answer 17

Severe anemia
Extramedullary erythropoeisis
Delayed sexual development
Poor growth
Elevated Hb F helps compensate
Death occurs by age 10 w/o early treatment w/ blood transfusions

Question 18

Beta-thal intermedia

Answer 18

Homozygotes with less severe mutations

Variable but decreased amounts of beta-chains produced (variable amounts of Hb A produced)

Question 19

Screening for hemoglobinopathies in pregnancy

Answer 19

African, Southeast Asian, Mediterranean descent should be offered carrier screening
- African - go directly to Hgb electrophoresis
- Start w/ CBC in others
- SE Asian - test for alpha-thal (molecular genetic testing)
Genetic counseling if both parents carriers

Question 20

Prenatal genetic testing

Answer 20

CVS or amniocentesis - DNA-based testing
- Sickle cell - diagnostic testing for single mutation
- Thal - can test if mutations have been identified in parents
Preimplantation genetic testing w/ IVF

Question 21

Risks of sickle cell disease in pregnancy

Answer 21

Maternal complications:
- Preterm labor
- PPROM
- Antepartum hospitalization
- PP infection
Fetal complications:
- SAB
- FGR
- Low birth weight
- IUFD

Question 22

Folic acid dose for SCD

Answer 22

4mg per day

- Due to continual turnover of red blood cells

Question 23

Precipitators of pain crises

Answer 23

Cold environment
Heavy physical exertion
Dehydration
Stress

Question 24

Hydroxyurea

Answer 24

Reduces frequency of painful crises

Teratogenic - do not use in pregnancy

Question 25

Management of pain crises

Answer 25

Prompt administration of analgesia
Opiates (PO, IV, IM)
Supplemental O2 if <95%
Evaluate for acute chest (fever, tachypnea, chest pain, hypoxia)

Question 26

Risks of prophylactic blood transfusion

Answer 26

Alloimmunization
Viral infections
Iron overload

Question 27

Indications for exchange transfusion

Answer 27

Worsening anemia
Intrapartum complications - hemororhage, sepsis, C/S
Painful crises
Acute chest syndrome

Question 28

Goal numbers for exchange transfusion

Answer 28

Hb S <40%

Total hgb ~10 g/dL

Question 29

Growth US/Antenatal testing in SCD

Answer 29

Reasonable due to increased risk for FGR and IUFD

Question 30

Pregnancy in beta-thal major

Answer 30

Previously uncommon due to delay in sexual development, early death, hypothalamic dysfunction/anovulation due to hemosiderin deposition
Recommended only in women w/ normal cardiac function, prolonged transfusion therapy to maintain hgb 10, iron chelation therapy (deferoxamine)

Question 31

Iron chelation therapy in pregnancy

Answer 31

Deferoxamine

Usually discontinued in pregnancy - safety has not been established

Question 32

Growth US/Antenatal testing in beta-thal major

Answer 32

Growths recommended

Antenatal testing if growth is suboptimal