Deck 10: Hemoglobinopaties: Qualitative Defects

Question 1

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

Answer 1

To increase the level of hemoglobin F that will reduce intracellular sickling

Question 2

Which of the following has the highest prevalence worldwide?

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

Answer 2

Hgb S

Question 3

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

Answer 3

Hemoglobin C

Question 4

Choose the defect from the choices below that will produce hemoglobin C disease.

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 5

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 ability of hemoglobin 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 6

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

A)Solubility is increased.
B)Change in the electrophoretic mobility
C)Increase in oxygen infinity
D)Increase in flexibility of the red blood cell

Question 7

Use this case to answer the following questions:
A 2-year-old black male was being evaluated at the County Clinic for swollen hands and feet that were extremely painful. Upon physical examination, the child was found to have a fever and hepatosplenomegaly, and was physically small for his age. The child was of Jamaican descent.
Patient history revealed that the child was normal for his birth weight, but since then, he was consistently underweight and undersized for his age group. Family history was not readily available. The physician had the child admitted to the hospital for workup and ordered the following CBC.
$\begin{array}{ll}\text { TEST } & \text { RESULTS } \\\text { WBC } & 16.6 \times 10^{9} / \mathrm{L} \\\text { RBC } & 2.53 \times 10^{12} / \mathrm{L} \\\text { HGB } & 7.5 \mathrm{gm} / \mathrm{dL} \\\text { HCT } & 21.4 \% \\\text { MCV } & 84.6 \mathrm{fl} \\\text { MCH } & 18.9 \mathrm{pg} \\\text { MCHC } & 35.0 \mathrm{~g} / \mathrm{dL} \\\text { RDW } & 18.9 \\\text { PLT } & 511 \times 10^{9} / \mathrm{L}\\\text { Differential: }\\\text { Polys } & 84 \% \\\text { Stabs } & 10 \% \\\text { Lymphs } & 5 \% \\\text { Eos } & 1 \% \\\text { NRBCs } & 12\end{array}$

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

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

Question 8

The strength and type of charge on the hemoglobin molecule will enable 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

Question 9

Disease that results from a molecular defect in hemoglobin synthesis in RBCs is termed:

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

Question 10

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

A)It cannot carry oxygen.
B)It forms insoluble aggregates.
C)It is unstable.
D)It has increased oxygen affinity.

Question 11

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

Question 12

A patient 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 of 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 13

Use this case to answer the following questions:
A 2-year-old black male was being evaluated at the County Clinic for swollen hands and feet that were extremely painful. Upon physical examination, the child was found to have a fever and hepatosplenomegaly, and was physically small for his age. The child was of Jamaican descent.
Patient history revealed that the child was normal for his birth weight, but since then, he was consistently underweight and undersized for his age group. Family history was not readily available. The physician had the child admitted to the hospital for workup and ordered the following CBC.
$\begin{array}{ll}\text { TEST } & \text { RESULTS } \\\text { WBC } & 16.6 \times 10^{9} / \mathrm{L} \\\text { RBC } & 2.53 \times 10^{12} / \mathrm{L} \\\text { HGB } & 7.5 \mathrm{gm} / \mathrm{dL} \\\text { HCT } & 21.4 \% \\\text { MCV } & 84.6 \mathrm{fl} \\\text { MCH } & 18.9 \mathrm{pg} \\\text { MCHC } & 35.0 \mathrm{~g} / \mathrm{dL} \\\text { RDW } & 18.9 \\\text { PLT } & 511 \times 10^{9} / \mathrm{L}\\\text { Differential: }\\\text { Polys } & 84 \% \\\text { Stabs } & 10 \% \\\text { Lymphs } & 5 \% \\\text { Eos } & 1 \% \\\text { NRBCs } & 12\end{array}$

-This patient presented with swollen hands and feet.What kind of crisis is this patient suffering from?

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

Question 14

Use this case to answer the following questions:
A 2-year-old black male was being evaluated at the County Clinic for swollen hands and feet that were extremely painful. Upon physical examination, the child was found to have a fever and hepatosplenomegaly, and was physically small for his age. The child was of Jamaican descent.
Patient history revealed that the child was normal for his birth weight, but since then, he was consistently underweight and undersized for his age group. Family history was not readily available. The physician had the child admitted to the hospital for workup and ordered the following CBC.
$\begin{array}{ll}\text { TEST } & \text { RESULTS } \\\text { WBC } & 16.6 \times 10^{9} / \mathrm{L} \\\text { RBC } & 2.53 \times 10^{12} / \mathrm{L} \\\text { HGB } & 7.5 \mathrm{gm} / \mathrm{dL} \\\text { HCT } & 21.4 \% \\\text { MCV } & 84.6 \mathrm{fl} \\\text { MCH } & 18.9 \mathrm{pg} \\\text { MCHC } & 35.0 \mathrm{~g} / \mathrm{dL} \\\text { RDW } & 18.9 \\\text { PLT } & 511 \times 10^{9} / \mathrm{L}\\\text { Differential: }\\\text { Polys } & 84 \% \\\text { Stabs } & 10 \% \\\text { Lymphs } & 5 \% \\\text { Eos } & 1 \% \\\text { NRBCs } & 12\end{array}$

-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

Question 15

Use this case to answer the following questions:
A 2-year-old black male was being evaluated at the County Clinic for swollen hands and feet that were extremely painful. Upon physical examination, the child was found to have a fever and hepatosplenomegaly, and was physically small for his age. The child was of Jamaican descent.
Patient history revealed that the child was normal for his birth weight, but since then, he was consistently underweight and undersized for his age group. Family history was not readily available. The physician had the child admitted to the hospital for workup and ordered the following CBC.
$\begin{array}{ll}\text { TEST } & \text { RESULTS } \\\text { WBC } & 16.6 \times 10^{9} / \mathrm{L} \\\text { RBC } & 2.53 \times 10^{12} / \mathrm{L} \\\text { HGB } & 7.5 \mathrm{gm} / \mathrm{dL} \\\text { HCT } & 21.4 \% \\\text { MCV } & 84.6 \mathrm{fl} \\\text { MCH } & 18.9 \mathrm{pg} \\\text { MCHC } & 35.0 \mathrm{~g} / \mathrm{dL} \\\text { RDW } & 18.9 \\\text { PLT } & 511 \times 10^{9} / \mathrm{L}\\\text { Differential: }\\\text { Polys } & 84 \% \\\text { Stabs } & 10 \% \\\text { Lymphs } & 5 \% \\\text { Eos } & 1 \% \\\text { NRBCs } & 12\end{array}$

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

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

Question 16

Hemoglobinopathies are detected by which laboratory method?

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 17

Evolution dictates that patients with sickle-cell disease have an inherent resistance to what?

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

Question 18

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 19

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 20

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 21

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

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

Question 22

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

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

Question 23

Use this case to answer the follwing questions:
During a discussion of RBC indices, a medical technologist of Cambodian origin mentioned that her own red cells were small in a CBC per?formed two years earlier in a routine physical. A more recent CBC showed the following results.
$\begin{array}{ll}\text { TEST } & \text { RESULTS } \\\text { WBC } & 9.3 \times 10^{9} / \mathrm{L} \\\text { RBC } & 6.11 \times 10^{12} / \mathrm{L} \\\mathrm{HGB} & 13.0 \mathrm{~g} / \mathrm{dL} \\\mathrm{HCT} & 41.8 \% \\\text { MCV } & 69.6 \mathrm{fL} \\\text { MCH } & 22.5 \mathrm{pg} \\\text { MCHC } & 31.0 \mathrm{~g} / \mathrm{dL} \\\mathrm{RDW} & 15.8 \\\mathrm{PLT} & 351 \times 10^{9} / \mathrm{L}\\\text { Differential }& \text { Within normal limits }\\\end{array}$

-What reflex test is most appropriate to investigate these results?

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

Question 24

Use this case to answer the follwing questions:
During a discussion of RBC indices, a medical technologist of Cambodian origin mentioned that her own red cells were small in a CBC per?formed two years earlier in a routine physical. A more recent CBC showed the following results.
$\begin{array}{ll}\text { TEST } & \text { RESULTS } \\\text { WBC } & 9.3 \times 10^{9} / \mathrm{L} \\\text { RBC } & 6.11 \times 10^{12} / \mathrm{L} \\\mathrm{HGB} & 13.0 \mathrm{~g} / \mathrm{dL} \\\mathrm{HCT} & 41.8 \% \\\text { MCV } & 69.6 \mathrm{fL} \\\text { MCH } & 22.5 \mathrm{pg} \\\text { MCHC } & 31.0 \mathrm{~g} / \mathrm{dL} \\\mathrm{RDW} & 15.8 \\\mathrm{PLT} & 351 \times 10^{9} / \mathrm{L}\\\text { Differential }& \text { Within normal limits }\\\end{array}$

-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 25

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 26

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

Question 27

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

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

Question 28

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 29

How is methemoglobin detected in the laboratory?

Question 30

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 31

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

Question 32

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 33

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

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