Hemoglobinopathies

Question 1

What chromosomes are responsible for having the alpha and beta globin gene loci, respectively?

Answer 1

Chr 16 - alpha globin gene loci

Chr 11 - beta globin gene loci

Question 2

What is the disorder resulting from imbalance between the amounts of alpha and beta globin chains that are synthesized?

Answer 2

Thalassemia

• distribution is associated with regions with high malaria infections.

Question 3

In general, alpha genes are affected by

Answer 3

full deletions

Question 4

In general, beta genes are affected by

Answer 4

point mutations

Question 5

Microcytosis with normal/mildly decreased hemoglobin values, and normal RBC survival are clinical presentations of

Answer 5

Either alpha thalassemia trait or B thalassemia trait

Question 6

If a mutation causes absent beta globin synthesis, it is

Answer 6

β0 thalassemia

Question 7

If a mutation causes decreased amounts of beta globin, it is

Answer 7

β+ thalassemia

Question 8

This severe anemia develops b/w 2 and 12 mo and not at birth because of HbF. Typically seen in Mediterraneans. Diagnosis by hemoglobin electrophoresis showing α4 tetramers and absence of normal HbA.

Symptoms include:
Anemia
Splenomegaly
Bony deformities
Those due to iron overload (bronze skin, liver failure, endocrine failure)

Answer 8

β Thalassemia major (Cooley’s Anemia) (β0/β0)

Question 9

What are the reasons of the symptoms of B Thalassemia Major?

Symptoms include:
Anemia
Splenomegaly
Bony deformities
Those due to iron overload (bronze skin, liver failure, endocrine failure)

Answer 9

α4 tetramers lead to major symptoms.

1. Anemia (due to ineffective erythropoiesis)
2. Splenomegaly (destruction of produced RBCs)
3. Skeletal deformities (due to frontal bossing or thinning of bone cortex to provide more room for the marrow)
4. Iron overload (due to transfusions and hyper-absorption of iron from gut)

Question 10

This is usually a heterozygous state—where one allele is normal and one allele is usually β+. Usually asymptomatic and no α4 tetramers.

Lab findings include: Very microcytic; May or may not be anemic; elevated RBC count; elevated HbA2; normal RDW (since ALL of the cells are microcytic and hypochromic)

Answer 10

Beta thalassemia minor (trait)

Question 11

Thalassemia which is typically silent.
May have minimal microcytosis.
Anemia not present.
Hg electrophoresis normal

Answer 11

αα/α-: one alpha gene deletion

Question 12

Thalassemia in which the patient will be mildly anemic (Hg 10-11), Microcytosis with MCV around 70.
Hgb electrophoresis normal in adults
Newborns will make “Hemoglobin Barts” (γ4), so the newborn screen (electrophoresis) will be abnormal

Answer 12

αα/– and α−/α− : Two gene deletions

Question 13

This disease forms an unstable Hb that precipitates as the RBC ages, forming Heinz bodies, which causes bite cells and a hemolytic anemia. Splenomegaly is common. β4 tetramers are formed. Low MCV and MCH, high RDW.

Answer 13

α-/–: Hemoglobin H disease

Question 14

This disease leads to no alpha chains forming. γ4 tetramers (Hemoglobin Barts) are formed. Intrauterine and stillbirth deaths are common. Can be treated in utero.

Answer 14

–/–: Hydrops fetalis

Question 15

This hemoglobin’s sixth amino acid in β chain is changed from glutamate (- charged) to valine (neutral, hydrophobic).

It is very insoluble compared to HbA and polymerizes to form a long fiber (cell sickling).

Answer 15

Hemoglobin S

Question 16

This hemoglobin’s sixth amino acid in β chain is changed from glutamate (-) to lysine (+). Leads to increased cellular dehydration

Answer 16

Hemoglobin C

Question 17

Under what conditions does Hb S polymerize and cells sickle?

Answer 17

Hypoxia and acidosis

Question 18

Eventual irreversible cell sickling is caused by

Answer 18

cellular dehydration

Question 19

What is the major outcome of permanent cell sickling?

Answer 19

Sickle cells have abnormal adhesion to endothelial cells due to its less deformable shape.

Question 20

What is the genotype that represents sickle cell anemia?

Answer 20

Homozygous SS

Question 21

What are the three genotypes that represent sickle cell disease?

Answer 21

SS

SC

S β-thalassemia

Question 22

Chronic hemolysis, anemia, functional asplenia (howell jolly bodies are seen on Peripheral blood smear), thrombosis (venous clots, PE, DVT) are clinical presentations of

Answer 22

SS patients

Question 23

This sickle cell crisis is caused by the rapid and extensive trapping of RBCs in spleen. Profound anemia, massive splenomegaly, hypovolemic shock—occurs quickly

Answer 23

Splenic sequestration crisis

Question 24

This sickle cell crisis is caused by Parvovirus B19 which leads to marrow suppression, with rapid development of anemia (but not so fast as in sequestration crisis)

Answer 24

Aplastic crisis

Question 25

This sickle cell crisis is most common and is caused by periodic episodes of severe pain resulting from acute vascular occlusion (obstruction). Attacks of pain affect bones and large joints.

Can be triggered by exercise, dehydration, infection, cold, stress, menstruation, surgery/trauma, pregnancy

Answer 25

Painful (Vaso-occlusive) episodes

Question 26

SS patients are at an increased risk of what organisms?

Answer 26

1. encapsulated organisms
2. yersinia or vibrio organisms if undergoing iron chelation therapy
3. salmonella osteomyelitis (found on reptiles)

Question 27

The most common cause of death in patients with sickle cell disease is?

Answer 27

Acute Chest Syndrome

Question 28

A patient that presents with Hypoxemia, a new infiltrate on CXR, new fever, chest pain, dyspnea, or cough
Acute worsening of anemia has?

Answer 28

Acute Chest Syndrome

Question 29

Infections with chlamydia and mycoplasma and fat embolism from necrotic bone marrow can lead to what clinical presentation of sickle cell anemia?

Answer 29

Acute Chest Syndrome

Question 30

What are the three ways we treat Acute Chest Syndrome?

Answer 30

Antibiotics, Oxygen, and Transfusion to lower HbS concentration (simple or exchange)

Question 31

What is the prevalence of Pulmonary Hypertension in adults with sickle cell disease?

Answer 31

one third of SCD adults

Question 32

The median age of stroke in patients with sickle cell anemia is?

Answer 32

5 years old (due to vasculopathy and not due to atherosclerosis like in adults)

• the circle of willis in the head can be visualized.

Question 33

Stroke in children with sickle cell anemia can be treated with?

Answer 33

exchange or chronic transfusion

Question 34

Iron overload in patients with sickle cell disease is treated with?

Answer 34

chelation

Question 35

What blood antigens must be negative/absent before transfusing blood to African-Americans with sickle cell anemia to prevent allo-antibodies from forming against donor RBCs?

Answer 35

C, E, Kell

Question 36

Treatment for sickle cell disease that increases amount of HbF, thus decreasing concentration of HbS.

Benefits:
Reduces number of sickle crises
Reduces episodes of acute chest syndrome
Prevents Pulmonary hypertension
Reduces mortality

Side effect: bone marrow suppression

Answer 36

Hydroxyurea

Question 37

Microcytosis, target cells, and splenomegaly, NOT anemic are clinical presentations of

Answer 37

Hemoglobin C disease

Question 38

Prevalence at birth of sickle cell anemia in African-Americans is what fraction?

Answer 38

1/500