MMSC433 Exam 2 Practice Questions

What is a hemoglobinopathy?

A. An acquired platelet disorder

B. An inherited or newly mutated disorder affecting hemoglobin synthesis or structure

C. A disorder involving only iron absorption

D. A disease caused exclusively by bone marrow failure

An inherited or newly mutated disorder affecting hemoglobin synthesis or structure

What is the main difference between qualitative and quantitative hemoglobinopathies?

A. Qualitative disorders affect iron; quantitative disorders affect platelets

B. Qualitative disorders alter globin structure; quantitative disorders reduce globin production

C. Qualitative disorders are always acquired

D. Quantitative disorders always cause sickle cells

Qualitative disorders alter globin structure; quantitative disorders reduce globin production

Which amino acid substitution causes HbS?

A. Lysine replaces glutamic acid at beta-6

B. Valine replaces glutamic acid at beta-6

C. Glutamic acid replaces valine at beta-6

D. Valine replaces lysine at beta-6

Valine replaces glutamic acid at beta-6

Which amino acid substitution is associated with HbC?

A. Valine for glutamic acid at beta-6

B. Lysine for glutamic acid at beta-6

C. Glycine for valine at alpha-6

D. Glutamic acid for lysine at beta-6

Lysine for glutamic acid at beta-6

Which finding is most characteristic of HbCC disease?

A. HbA above 90%

B. HbS above 80%

C. HbC usually above 90%, with absent HbA

D. HbA and HbS each around 50%

HbC usually above 90%, with absent HbA

Which hemoglobin pattern is most consistent with sickle cell trait (HbAS)?

A. HbS only

B. HbA around 60% and HbS around 40%

C. HbC around 90%

D. HbF is always predominant

HbA around 60% and HbS around 40%

Which finding distinguishes HbSS disease from HbAS trait?

A. Presence of any HbS

B. Absence of HbA in typical HbSS

C. Normal MCV in every patient with HbSS

D. Presence of HbF only in trait

Presence of HbF only in trait

What is acute chest syndrome?

A mild chronic cough without imaging changes

A. A mild chronic cough without imaging changes

B. A life-threatening complication involving respiratory symptoms and a new pulmonary infiltrate

C. A condition caused exclusively by iron deficiency

D. A synonym for aplastic crisis

A life-threatening complication involving respiratory symptoms and a new pulmonary infiltrate

Which organism is associated with aplastic crisis in sickle cell disease?

A. Parvovirus B19

B. Plasmodium vivax

C. Candida albicans

D. Helicobacter pylori

Parvovirus B19

What causes autosplenectomy in sickle cell disease?

A. Excessive iron absorption alone

B. Repeated splenic vaso-occlusion and infarction

C. Increased platelet production

D. Excessive HbA production

Repeated splenic vaso-occlusion and infarction

What is the primary mechanism of thalassemia?

A. Production of structurally abnormal platelets

B. Reduced production of one or more globin chains

C. Excessive production of normal hemoglobin in all cases

D. Deficiency of beta-glucocerebrosidase

Reduced production of one or more globin chains

Which CBC pattern is common in thalassemia?

A. High MCV and high MCHC

B. Low MCV and low MCH, often with a normal or relatively high RBC count

C. High MCV and low RBC count in every case

D. Normal indices in all forms

Low MCV and low MCH, often with a normal or relatively high RBC count

Which hemoglobin is often markedly increased in beta-thalassemia major?

A. HbA

B. HbF

C. HbC

D. HbS

HbF

What does beta-zero (β⁰) thalassemia mean?

A. Normal beta-globin production

B. Reduced but preserved beta-globin production

C. No beta-globin production from the affected allele

D. Deletion of all four alpha-globin genes

No beta-globin production from the affected allele

How many alpha-globin gene deletions are typically associated with HbH disease?

A. One

B. Two

C. Three

D. Four

Three

What is the composition of Hb Bart's?

A. Four alpha chains

B. Four beta chains

C. Four gamma chains

D. Two alpha and two beta chains

Four gamma chains

Which finding is characteristic of severe beta-thalassemia major?

A. Chipmunk facies from expansion of marrow spaces

B. A completely normal blood smear

C. High MCV with macro-ovalocytes only

D. Isolated thrombocytosis without anemia

Chipmunk facies from expansion of marrow spaces

Why can iron overload develop in thalassemia major?

A. The body loses all ability to excrete bilirubin

B. Repeated transfusions and increased intestinal iron absorption

C. HbF directly converts into iron

D. Low MCV creates iron

Repeated transfusions and increased intestinal iron absorption

How does hydroxyurea help many patients with sickle cell disease?

A. It eliminates every HbS gene

B. It increases HbF and reduces sickling and vaso-occlusive events

C. It increases iron absorption

D. It converts HbS into HbC

It increases HbF and reduces sickling and vaso-occlusive events

What does a positive hemoglobin solubility test indicate?

A. HbSS is definitively confirmed

B. HbAS is definitively confirmed

C. HbS is likely present, requiring confirmatory testing

D. The percentage of HbS is precisely known

HbS is likely present, requiring confirmatory testing

Which test separates and quantifies hemoglobin fractions such as HbA2, HbF, HbS, and HbC?

A. ESR

B. HPLC

C. Bleeding time

D. Direct antiglobulin test

HPLC

What is the main purpose of iron studies in a patient with microcytosis?

A. Confirm HbS polymerization

B. Help distinguish iron deficiency anemia from thalassemia

C. Measure CD34 expression

D. Diagnose Gaucher disease directly

Help distinguish iron deficiency anemia from thalassemia

What is the primary enzyme deficiency in Gaucher disease?

A. Sphingomyelinase

B. Beta-hexosaminidase A

C. Beta-glucocerebrosidase

D. Glucose-6-phosphate dehydrogenase

Beta-glucocerebrosidase

Which enzyme deficiency is associated with Tay-Sachs disease?

A. Beta-hexosaminidase A

B. Beta-glucocerebrosidase

C. Sphingomyelinase

D. Alpha-globin synthase

Beta-hexosaminidase A

What accumulates in Niemann-Pick disease types A and B?

A. Glucocerebroside due to beta-glucocerebrosidase deficiency

B. Sphingomyelin due to sphingomyelinase deficiency

C. HbS due to beta-globin mutation

D. Iron due to transfusion alone

Sphingomyelin due to sphingomyelinase deficiency

In flow cytometry, forward scatter (FSC) most closely correlates with:

A. Cell size

B. Cell granularity only

C. Hemoglobin electrophoretic mobility

D. Specific antibody concentration only

Cell size

In flow cytometry, side scatter (SSC) most closely reflects:

A. Cell size only

B. Cell internal complexity or granularity

C. The patient's hemoglobin percentage

D. The speed of DNA replication only

Cell internal complexity or granularity

What is hydrodynamic focusing?

A. Separating HbA from HbS using acid pH

B. Using sheath fluid to align cells in a narrow stream

C. Selecting only CD19-positive cells

D. Measuring iron in plasma

Using sheath fluid to align cells in a narrow stream

Which marker is associated with hematopoietic stem/progenitor cells?

A. CD19

B. CD235a

C. CD34

D. CD20

CD34

Which marker is associated with erythroid precursors?

A. CD71

B. CD19

C. CD22

D. CD20

CD71

A 19-year-old has recurrent severe pain crises, a history of acute chest syndrome, and evidence of functional asplenia. The smear shows sickle cells, target cells, and nucleated RBCs. HPLC shows HbS 88%, HbF 9%, and no HbA. What is the diagnosis?

Sickle cell disease (HbSS)

A healthy 22-year-old is found to have HbA 61% and HbS 39% during screening. The CBC and smear are essentially normal. What is the diagnosis?

Sickle cell trait (HbAS)

A patient has mild to moderate hemolytic anemia, splenomegaly, target cells, microspherocytes, and HbC crystals. Hemoglobin analysis shows HbC above 90% and no HbA. What is the diagnosis?

Hemoglobin C disease (HbCC)

A patient has pain episodes and hemolytic anemia. The hemoglobin analysis shows approximately 50% HbS and 50% HbC, with no HbA. What is the diagnosis?

Hemoglobin SC disease (HbSC)

A child has severe anemia beginning in infancy, growth delay, hepatosplenomegaly, marked microcytosis, hypochromia, target cells, and nucleated RBCs. HbF is markedly increased and HbA is absent. What is the most likely diagnosis?

Beta-thalassemia major, consistent with beta-zero disease.

A 20-year-old has no symptoms but has a low MCV, low MCH, target cells, and an RBC count that is relatively high for the degree of anemia. HbA is predominant and HbA2 is 5%. What is the most likely diagnosis?

Beta-thalassemia minor (trait).

A patient has lifelong mild microcytosis with minimal anemia. Iron studies are normal. Hemoglobin analysis does not show a significant abnormal variant. Genetic testing identifies two deleted alpha-globin genes. What is the diagnosis?

Alpha thalassemia trait

A patient has chronic hemolytic anemia, marked microcytosis, hypochromia, target cells, and HbH inclusions on brilliant cresyl blue staining. What is the diagnosis?

HbH disease (3 affected alpha-globin genes)

A fetus has profound anemia, generalized edema, and evidence of hydrops fetalis. Testing indicates deletion of all four alpha-globin genes. Which hemoglobin is expected?

Hb Bart's (γ₄), associated with alpha-thalassemia major

A patient has severe anemia and a smear showing sickle cells, target cells, microcytic hypochromic RBCs, polychromasia, and anisopoikilocytosis. Hemoglobin analysis shows HbS with no HbA and increased HbF. What combined disorder should be considered?

Sickle-beta-zero thalassemia

A patient with chronic transfusion-dependent thalassemia develops cardiac dysfunction, liver abnormalities, and endocrine problems. What complication is most likely?

Iron overload

A patient with sickle cell disease develops fever, chest pain, tachypnea, low oxygen saturation, and a new infiltrate on chest radiograph. What complication is present?

Acute chest syndrome

A patient with sickle cell disease suddenly develops profound anemia and a very low reticulocyte count after a viral illness. What complication is likely?

Aplastic crisis due to parvovirus B19

A patient has chronic hemolysis, splenomegaly, and numerous target cells. The laboratory reports glutamic acid replaced by lysine at beta-globin position 6. What hemoglobin variant is present?

Hemoglobin C

Which hemoglobin is typically absent in HbSS disease?

A. HbS

B. HbF

C. HbA

D. HbA2

HbA

Which pattern is typical of HbAS?

A. HbS 90%, HbA absent

B. HbA 55-65%, HbS 35-45%

C. HbC above 90%

D. HbF almost 100%

HbA 55-65%, HbS 35-45%

Which pattern is typical of HbCC?

A. HbA above 90%

B. HbS and HbC each around 50%

C. HbC usually above 90%, HbA absent

D. HbA and HbS each around 40%

HbC usually above 90%, HbA absent

Which result supports beta-thalassemia minor?

A. HbA2 1%

B. HbA2 5% with predominant HbA

C. HbS 90% and no HbA

D. HbC 95%

HbA2 5% with predominant HbA

Which hemoglobin is often predominant in beta-thalassemia major?

A. HbF

B. HbA

C. HbC

D. HbA2 alone

HbF

What does HbA2 usually look like in beta-thalassemia minor?

A. Usually above 3.5%

B. Always absent

C. Usually above 90%

D. Always exactly 50%

Usually above 3.5%

A hemoglobin study shows no HbA, HbS approximately 50%, and HbC approximately 50%. Which diagnosis fits?

A. HbAS

B. HbAC

C. HbSS

D. HbSC

HbSC

Why should HbF be considered when interpreting a sickle solubility test in a newborn?

A. HbF can cause a false-positive iron study

B. High HbF may cause a false-negative solubility screen

C. HbF confirms HbCC

D. HbF makes electrophoresis unnecessary

High HbF may cause a false-negative solubility screen

Which combination is most suggestive of thalassemia rather than iron deficiency alone?

A. Low MCV and increased HbA2

B. High MCV and low HbA2

C. Normal MCV and HbS 90%

D. High MCHC and no anemia

Low MCV and increased HbA2

A patient has low MCV and low MCHC. Which additional test is especially useful to help separate iron deficiency from thalassemia?

A. Iron studies

B. Solubility testing alone

C. CD19 analysis

D. Acid electrophoresis alone

Iron studies

At alkaline pH, which hemoglobin is the fastest major adult hemoglobin in your course notes?

HbA

Which hemoglobins can co-migrate with HbS at alkaline pH?

HbD and HbG

Which hemoglobins can co-migrate with HbC at alkaline pH?

HbE and HbA2

Why is alkaline electrophoresis alone insufficient to definitively identify every hemoglobin variant?

Some variants share migration positions

Which hemoglobins are separated from HbS by acid electrophoresis?

HbD and HbG are separated from HbS

Which hemoglobins are separated from HbC by acid electrophoresis?

HbE and HbO

A patient has a positive solubility test. What additional testing should be performed to distinguish sickle cell trait from sickle cell disease?

Hemoglobin electrophoresis or HPLC

Why may a solubility test be falsely negative in newborns?

High HbF and low HbS can produce a false-negative screen.

Which technique separates and quantifies hemoglobin fractions using chromatographic retention?

HPLC

What is the difference between identifying the presence of HbS and determining its percentage?

Detection is qualitative; quantification measures the proportion of each hemoglobin.

A patient has macrophages with wrinkled, crumpled tissue-paper cytoplasm in the bone marrow. The enzyme deficiency is beta-glucocerebrosidase.

Gaucher disease

An infant develops failure to thrive, hepatosplenomegaly, and rapid neurodegeneration. Sphingomyelinase activity is deficient.

Niemann-Pick type A

A patient has progressive hepatosplenomegaly, thrombocytopenia, and relatively little neurological involvement compared with type A

Niemann-Pick type B

A patient develops progressive neurological and psychiatric symptoms with intracellular cholesterol accumulation due to NPC1 or NPC2 mutations

Niemann-Pick type C

A child develops severe neurodegeneration associated with beta-hexosaminidase A deficiency

Tay-Sachs disease

A patient develops hepatosplenomegaly and bone crises but has no primary neurodegenerative course

Gaucher type I (non-neuropathic Gaucher disease)

An infant has rapidly progressive neurological disease and severe visceral involvement, with a typical life expectancy of around two years in classic cases

Gaucher type II

A child develops a more slowly progressive neurological disorder along with skeletal complications

Gaucher type III

The hemoglobin solubility test is a:

qualitative test for sickle cell disease

quantitative test for sickle cell disease

a confirmatory test for sickle cell disease

a definitive test for sickle disease

qualitative test for sickle cell disease

Cellulose acetate is performed on a patient with known homozygous HbS who has received red cell transfusions in the past week. What hemoglobins would be expected to be found?

Hb S, Hb A, Hb F, Hb A2

Hb S and Hb F

Hb A and Hb F

Hb S, Hb A, and Hb F

Hb S, Hb A, Hb F, Hb A2

Is a Cellulose acetate test alkaline or acid?

alkaline

What is the major hemoglobin found in red cells of patients with sickle cell trait?

Hgb A

Hgb S

Hgb F

Hgb A2

Hgb A

Select the amino acid substitution that is responsible for sickle cell anemia

A. Valine is substituted for glutamic acid at 6th position of beta chain

B. lysine is substituted for glutamic acid at 6th position of alpha chain

C. Valine is substituted for glutamic acid at 6th position of alpha chain

D. Glutamine is substituted for glutamic acid at 6th position of beta chain

Valine is substituted for glutamic acid at 6th position of beta chain

Which of the following hemoglobins migrate to the same position as Hgb A2 at pH 8.6?

Hgb C

Hgb H

Hgb F

Hgb S

Hgb C

Which of the following electrophoretic results is consistent with a diagnosis of sickle cell trait?

Hgb A 60%, Hgb S 40%, Hgb A2 2%

Hgb A 40%, Hgb S 35%, Hgb F 5%

Hgb A 0%, Hgb A2 5%, Hgb F 95%

Hgb A 80%, Hgb S 10%, Hgb A2 10%

Hgb A 60%, Hgb S 40%, Hgb A2 2%

What percent of offspring will have sickle trait when the mother has sickle trait (AS) and father is normal (AA).

50%

25%

75%

100%

50%

This condition of sickle cell anemia is characterized by fever, chest pain, and presence of pulmonary infiltrates on the chest radiograph and is the leading cause of death among adults with sickle cell disease.

Acute chest syndrome

hand-foot syndrome

septicemia

avascular necrosis

Acute chest syndrome

What is true regarding Hgb C disease?

Hgb C is present at levels greater than 90%

hemoglobin solubility test is positive

cellulose acetate is more useful than citrate agar on electrophoresis

Hgb C is present at levels less than 90%

Hgb C is present at levels greater than 90%

How is Hemoglobin Barts symbolized?

Gamma 4

Beta 4

Delta 4

Alpha 4

Gamma 4

A 29-year-old female has been experiencing fatigue and sudden pain in her joints. She presents with decreased levels of hemoglobin, increased bilirubin, and the presence of crescent moon-shaped cells on her peripheral smear. Which of the following is the most likely diagnosis for this patient?

Sickle cell disease

Sickle cell trait

hemoglobin C disease

Beta thalassemia

Sickle cell disease

What is the reason for the sickle-shaped RBC seen in sickle cell disease?

Increased production of β-globin chains causing excess hemoglobin to accumulate within the RBC.

Decreased production of β-globin chains causing the RBCs to become small and rigid.

Valine substitution for glutamic acid at the 6th position of the beta chain of hemoglobin.

Lysine substitution for glutamic acid at the 6th position of the beta chain of hemoglobin

Valine substitution for glutamic acid at the 6th position of the beta chain of hemoglobin.

A patient presents to the ED and reports recent flank pain on her vacation in Colorado. Upon arrival labs are ordered. Her labs show a reticulocyte count of 15% (elevated) as well as HJ bodies and sideroblastic granules on a peripheral smear. It is discovered that her Hgb A is 60% and her Hgb s is about 40%. Which diagnoses are these results indicative of?

Sickle cell anemia

Hemoglobin C disease

Double dose of the abnormal gene that codes for HbS

Sickle cell trait

Sickle cell trait

As part of a sickle cell crisis, sickled cells get trapped in microvessels causing obstruction of blood flow to organs. This may also be accompanied by fever and increased WBC, as well as intense pain. What is the name of this manifestation?

acute chest syndrome

vaso-occlusion

AVN

autosplenectomy

vaso-occlusion

An amino acid substitution mutation involving glutamic acid that is replaced by valine on one beta globulin chain and by lysine on the other beta globulin chain at position 6 (α₂β 6𝐺𝑙𝑢−𝑉𝑎𝑙 β ) as a result of inheriting each substitution from each parent is the etiology for which of 6𝐺𝑙𝑢−𝑙𝑦𝑠 the following diseases?

Hemoglobin C disease

Hemoglobin SC disease

Sickle cell anemia

hemoglobin D

Hemoglobin SC disease

Infrequent vaso-occlusive crisis, moderate hemolytic anemia, splenomegaly, and respiratory tract infections with S. pnuemoniae are symptoms of which of the following disease?

Hemoglobin D

unstable hemoglobin

Hemoglobin M

Sickle cell anemia

Hemoglobin D

A patient's hemoglobin electrophoresis shows about 50% HbS and 50% HbC, with no HbA detection. The peripheral smear includes target cells and a characteristic "boat-shaped" appearance. Which diagnosis is the most likely?

Sickle cell trait

Sickle cell disease

Hemoglobin SC disease

Hemoglobin C disease

Hemoglobin SC disease

Which laboratory finding would be the best to distinguish between sickle cell trait (HbAS) and sickle cell disease (HbSS)?

Presence of HbS

Presence of HbA

Increased reticulocyte count

Positive sickling/solubility test

Presence of HbA

What kind of testing is required to determine a definitive diagnosis for Hemoglobin C disease?

Spectrophotometry

Acidic electrophoresis

Solubility test

All of the above

Acidic electrophoresis

Target cells, microspherocytes, schistocytes, as well as "bars of gold" crystals appear in a patient's peripheral blood smear. What does this specific morphology tell us about the patient's diagnosis?

Hemoglobin C disease

Sickle cell disease

Sickle cell trait

Hemoglobin SC disease

Hemoglobin C disease