Blood Disorders ALC Epidemiology

Question 1

What are thalassemia (generally)

Answer 1

Quantitative defects in global chain. This can impact both alpha and beta Hb.

Question 2

How do thalassemia’s cause disease?

Answer 2

Since there is insufficient Hb, unpaired globing chains precipitate which leads to damage of the RBC interior and membrane, ultimately causing RBC death.

Question 3

Which statement is correct?

A) Blood from a patient with thalassemia and anemia has normal oxygen content

B) SCD and thalassemia cause painful ‘crises’

C) SCD and G6PD deficiency result in enzyme dysfunction

D) SCD and G6PD deficiency disease expression is highly variable

Answer 3

D

Question 4

What is sickle cell disease (generally)

Answer 4

A qualitative defect in Hb. There is a mutation in the beta globin gene that causes exposure of a lysine residues on the beta globin when Hb is in the deoxygenated state. This induces shape changes in adjacent globin chains and causes the molecule of Hb to become less soluble and precipitate out of solution. Exposure of these hydrophobic residues promotes aggregation of these insoluble Hb molecules, which can damage components of the RBC membrane. The RBC does not have any means of repairing that damage, so this is irreversible and ultimately causes the cell to change shape (sickling) and eventually lyse.

Question 5

What is G6PD deficiency (generally)

Answer 5

Insufficient amount of G6PD –> produced as part of PPP and is required by RBC to produce NADPH b/c RBC lacks mitochondria so this is the only source of NADPH. NADPH is needed to detoxify ROS. When insufficient G6PD is made the RBC is less able to deal with ROS produced from cellular metabolism, leading to early lysis.

Question 6

______ is the most common hemoglobinopathy in the US

Answer 6

Sickle Cell Disease

Question 7

A one-year-old boy, living in Nigeria, has failure to grow and gain weight (failure to thrive). He seems irritable. He is seen in the community health clinic where the diagnosis of sickle cell anemia (HbSS) is made. In addition to trying to optimize nutrition, which of the following would be the most appropriate intervention at this time?

a. Treatment for malaria
b. Bone marrow transplantation
c. Supplemental oxygen treatment at home
d. Antibiotic prophylaxis

Answer 7

D - patient’s with SCD are at increased risk for bacterial infections and that can often be what they die from

Question 8

Why is it so difficult to estimate the impact of SCD in the US?

Answer 8

• There is no central system tracking cases

- The disease is highly polymorphic

Question 9

What measures increase SCD survival?

Answer 9

• Screening
• Prophylaxis with antibiotics and vaccination
• Treatment - hydroxyurea –> boosts amount of fetal Hb, which is not defective so these patients are able to improve oxygenation and also reduce the amount of defective Beta Hb that is made so less polymerizes and causes damage
• Transfusions

Question 10

How are thalassemia’s inherited?

Answer 10

Autosomal recessive

Question 11

What is the difference between thalassemia major and minor?

Answer 11

Major = homozygous (also called Cooley's anemia)
Minor = heterozygous

Question 12

Is thalassemia polymorphic?

Answer 12

Yes - heterozygotes are mostly asymptomatic or have milder symptoms but homozygous individuals often require blood transfusions and may even need splenectomy due to enlargement/failure of spleen. The spleen filters our blood, so it can accumulate degradation products from increased hemolysis seen in thalassemia and become enlarged and damaged itself.

Question 13

Thalassemia patients often require frequent transfusion. What is a major concern with this treatment?

Answer 13

Iron overload

Question 14

What is the most common enzyme defect in humans?

Answer 14

G6PD

Question 15

How is G6PD inherited?

Answer 15

X-linked

Question 16

How does G6PD manifest clinically?

Answer 16

Severe jaundice
Kernicterus (brain damage from build up of bilirubin)
Acute hemolytic anemia

Question 17

What must be avoided with G6PD deficiency?

Answer 17

Fava beans
Aspirin
Sulfa antibiotics
Anti-malarials
Quinine/quinone
NSAIDs

Question 18

Genetic screening may overestimate the population impact of G6PD deficiency. This is due to which of the following?

A) Too many persons may choose to be screened
B) Presence of defective gene may not correlate with enzyme activity
C) There is no effective cure for the disease
D) The genetic test (gene sequencing) may also include hemoglobin disorders

Answer 18

B

Question 19

A 15-year-old boy has been receiving monthly RBC transfusions at the local hematology clinic in the city of Palermo, Italy. He was diagnosed with severe β thalassemia shortly after birth.

Which of the following is he most at risk of developing?

a. Heart disease secondary to iron overload
b. Abrupt hemolysis due to ingestion of fava beans
c. Vaso-occlusive painful episodes due to ischemia
d. Severe infection with malaria

Answer 19

A

Question 20

How do sickle cell, thalassemia, and G6PD protect someone against malaria?

Answer 20

In a normal person, malaria is a parasitic infection that infects a person’s RBCs.

SCD: Cells don’t survive long enough for parasite to infect successfully.

Thalassemia: Impaired parasite growth and enhanced clearance of infected RBCs

G6PD: May impair parasite growth due to susceptibility to oxidants

Question 21

Mr. and Mrs. Xu each report a family history of G6PD deficiency. They seek screening for the disease before starting a family and opt for genetic testing over spot blood assay. Which statement about genetic testing is most accurate?

Genetic testing…
A) Indicates whether their children will be symptomatic
B) Identifies which drugs will trigger hemolysis
C) Identifies all persons with sequence abnormalities
D) Measures the degree of enzyme deficiency

Answer 21

C

Question 22

Mr. and Mrs. K , who recently immigrated from rural Kenya, bring their 2-year old child in for her first well visit. Both parents have SCD. In addition to initiating the childhood vaccination series, what other recommendations would be advised?

A) Empiric treatment for malaria
B) Prophylactic penicillin
C) Prophylactic transfusion
D) Avoidance of fava beans

Answer 22

B

Question 23

All 50 states and the District of Columbia now mandate newborn screening for sickle cell disease. These data are at greatest risk of error in estimating the prevalence of sickle cell disease in states with which of the following?

A) High disparities in socio-economic status
B) High overall mortality rates
C) High proportions of Black or Hispanic populations
D) High rates of immigration

Answer 23

D

Question 24

To improve family practitioner’s comfort level in caring for individuals living with SCD one could expect success with which of the following interventions?

A) Develop a primer on transfusion medicine for all family practice providers
B) Have immediate availability of a physician trained in pain management to consult on patient care issues
C) Develop educational material that could help clinical decision making
D) Limit the number of patients with SCD in any given practice
Add social work support to the office staff

Answer 24

C