Deck 13: Hemoglobinopathies: Qualitative Defects

Question 1

The strength and type of charge on a hemoglobin molecule enables the separation of hemoglobin variants by electrophoresis. What other significant factor controls this separation?

A) Solubility of the molecule
B) pH of the medium
C) Heat precipitation
D) Elevation of hemoglobin concentration

Answer 1

pH of the medium

Question 2

Based on these findings, what test would be the logical next step?

A) Bone marrow aspirate
B) Osmotic fragility
C) Sickle solubility test
D) Peripheral blood smear

Answer 2

Sickle solubility test

Question 3

Clinical disease that results from a genetic mutation in one or more genes that affects hemoglobin synthesis is termed:

A) Thalassemia
B) Hemoglobinopathy
C) Porphyria
D) Asynchrony

Answer 3

Hemoglobinopathy

Question 4

Which laboratory method detects hemoglobinopathies?

A) Spectrophotometric analysis at 450 nm
B) Careful examination of peripheral blood cellular components
C) Separation and quantification of protein subunits through an electrical field
D) Turbidimetric analysis of whole blood

Question 5

Hemoglobin C disease has altered solubility properties similar to hemoglobin S disease. What accounts for this altered solubility?

A) Heme iron is in the ferric form rather than ferrous form.
B) The hemoglobin remains in the tense structure.
C) A nonpolar amino acid is substituted for a polar amino acid.
D) A polar amino acid is substituted near the pocket where heme binds.

Question 6

What is the purpose of treating sickle cell patients with hydroxyurea?

A) To dilute the amount of sickled red blood cells
B) To destroy the sickling red blood cells by initiating an immune response
C) To convert Hgb S into Hgb A
D) To increase the level of hemoglobin F that will reduce intracellular sickling

Question 7

All of the following parameters of the complete blood count are abnormal except:

A) Hemoglobin
B) MCV
C) RBCs
D) Platelet count

Question 8

In hemoglobin C disease, how does the mutation affect the hemoglobin molecule?

A) It cannot carry oxygen.
B) It has decreased hemoglobin solubility.
C) It is unstable.
D) It has increased oxygen affinity.

Question 9

Which of the following patients would have the highest percentage of hemoglobin S?

A) A neonate with sickle cell disease
B) An adult with sickle cell disease
C) An adult with sickle cell trait
D) An adult with SC disease

Question 10

The net decrease in negative charge in the hemoglobin S molecule is responsible for which laboratory finding?

A) Increase in solubility
B) Change in the electrophoretic mobility
C) Increase in oxygen infinity
D) Increase in flexibility of the red blood cell

Question 11

Evolution dictates that patients with sickle cell disease have an inherent resistance to which of the following?

A) Babesia infections
B) Acute leukemia
C) Hemolytic transfusion reactions
D) Plasmodium infections

Question 12

The peripheral blood smear contains a normocytic, normochromic morphology with marked reticulocytosis. The hemoglobin solubility test is positive. What confirmatory test should follow?

A) Bilirubin analysis
B) Haptoglobin analysis
C) Hemoglobin electrophoresis
D) Bone marrow aspiration

Question 13

Thalassemias are produced as a result of:

A) Quantitative defects in globin chain synthesis
B) Qualitative defects in globin chain synthesis
C) Structural defects in heme synthesis
D) Molecular defects in hemoglobin synthesis

Question 14

A patient's sample is run on cellulose acetate, and two bands are found. The first band migrates to the A region on the gel. The second band migrates to the S-D-G region on the band. What is the next step to identify the second band?

A) Perform electrophoresis on citrate agar at pH 6.2
B) Perform an osmotic fragility test
C) Perform an acid elution test
D) Do a supravital stain for Heinz bodies

Question 15

The defect that will produce hemoglobin C disease is:

A) Beta 6 substitution of glutamic acid for valine
B) Beta 6 substitution of lysine for glutamic acid
C) Alpha 26 substitution of glutamic acid for threonine
D) Alpha 4 substitution of thymidine for methionine

Question 16

Which abnormal hemoglobin is slow moving and migrates closely with hemoglobin A2 on cellulose acetate at an alkaline pH?

A) Hemoglobin S
B) Hemoglobin D
C) Hemoglobin M
D) Hemoglobin C

Question 17

Patients with sickle cell disease suffer from vaso-occlusive crises because:

A) The altered hemoglobin facilitates the formation of bar-shaped hemoglobin crystals that occlude blood vessels.
B) The altered hemoglobin impairs the hemoglobin's ability to effectively transport oxygen that causes vaso-occlusion.
C) The altered hemoglobin facilitates tactoid crystal formation that alters the shape of the red blood cell, resulting in impeded blood flow in vessels.
D) The altered hemoglobin interferes with globin chain assembly, which impedes blood flow in the vessels.

Question 18

Hemoglobinopathy results from a genetic abnormality of which structure within the hemoglobin molecule?

A) Globin chain
B) Heme
C) Porphyrin
D) Iron

Question 19

This patient presented with swollen hands and feet. This patient suffering from what kind of crisis?

A) Vaso-occlusive
B) Oxidative
C) Transfusion reaction
D) Anaphylactic reaction

Question 20

Which of the following has the highest prevalence worldwide?

A) Hgb S
B) Hgb C
C) Hgb D
D) Hgb E

Question 21

Other than hemoglobin S, name two abnormal hemoglobins that produce a positive sickle solubility test. Explain how they could be differentiated from HbS.

Question 22

Based on the demographics of this patient, what disorder is suspected?

A) Sickle cell disease
B) Hemoglobin C disease
C) Hemoglobin SC disease
D) Hemoglobin E disease

Question 23

If a patient had hemoglobin S and hemoglobin A identified by electrophoresis and a positive hemoglobin solubility test, what is the patient's most likely condition?

A) Hemoglobin C trait
B) Hemoglobin S/D disease
C) Hemoglobin SC disease
D) Sickle cell trait

Question 24

In hemoglobin C disease, the cell's life span is decreased to what length?

A) 90-120 days
B) 7-10 days
C) 75-90 days
D) 30-55 days

Question 25

Explain how methemoglobin is formed and how its presence impacts oxygen delivery. Be sure to include oxygen affinity in your answer.

Question 26

Both hemoglobin D and G migrate with which hemoglobin on alkaline gel electrophoresis?

A) S
B) A
C) F
D) C

Question 27

A patient has a positive sickle solubility test. Further investigation reveals hemoglobin of 8.5 g/dL. What can be done to confirm these findings? Explain your answer.

Question 28

Electrophoresis at an acid pH using a citrate agar gel separates what hemoglobin variants that travel together on cellulose acetate at pH 8.6?

A) Hemoglobins A and S
B) Hemoglobins S and C
C) Hemoglobins D and S
D) Hemoglobins E and A

Question 29

What reflex test is most appropriate for investigating these results?

A) Hemoglobin electrophoresis and iron studies
B) Bone marrow aspirate
C) Vitamin B₁₂ and folate assays
D) Cytogenetic analysis

Question 30

Patients with sickle cell disease and those with sickle cell trait differ greatly in clinical presentation. List at least two features in clinical presentation, and explain why they differ.

Question 31

What preoperative therapy is effective in a diagnosed sickle cell patient?

A) Stem cell transplant
B) Transfusion of red blood cells
C) Hydroxyurea administration
D) Gene therapy

Question 32

Sickle cell trait is not as severe as sickle cell anemia, so why is the sickle cell trait important to diagnose?

A) One in four children born to trait parents have the disease.
B) Sickle cell trait can mask other diseases.
C) Doing so eliminates the need for pharmacologic agent treatment.
D) Cells still sickle under the same conditions as with the disease.

Question 33

How is methemoglobin detected in the laboratory?