2 NORMOCYTIC AND NORMOCHROMIC ANEMIAS

Question 1

(1) Hypersplenism is characterized by:

A. Polycythemia
B. Pancytosis
C. Leukopenia
D. Myelodysplasia

Answer 1

C. Leukopenia

Hypersplenic conditions are generally described by the following four criteria: (1) cytopenias of one or more peripheral cell lines, (2) splenomegaly, (3) bone marrow hyperplasia, and (4) resolution of cytopenia by splenectomy.

Question 2

(2) Which of the following organs is responsible for the “pitting process” in RBCs?

A. Liver
B. Spleen
C. Kidney
D. Lymph nodes

Answer 2

B. Spleen

The spleen is the supreme filter of the body, pitting imperfections from the erythrocyte without destroying the integrity of the membrane.

Question 3

(3) Spherocytes differ from normal RBCs in all of the following except:

A. Decreased surface to volume
B. No central pallor
C. Decreased resistance to hypotonic saline
D. Increased deformability

Answer 3

D. Increased deformability

Spherocytes lose their deformability because of a defect in spectrin, a membrane protein, and are therefore prone to splenic sequestration and hemolysis

Question 4

(4) Which of the following is not associated with HS?

A. Increased osmotic fragility
B. MCHC greater than 36%
C. Intravascular hemolysis
D. Extravascular hemolysis

Answer 4

C. Intravascular hemolysis

Classic features of intravascular hemolysis, such as hemoglobinemia, hemoglobinuria, or hemosiderinuria, do not occur in HS. The hemolysis seen in HS is an extravascular process, rather than an intravascular process.

Question 5

(5) Which of the following disorders has an increase in osmotic fragility?

A. Iron deficiency anemia (IDA)
B. Hereditary elliptocytosis (HE)
C. Hereditary stomatocytosis
D. Hereditary spherocytosis (HS)

Answer 5

D. Hereditary spherocytosis (HS)

Spherocytic cells have decreased tolerance to swelling and, therefore, hemolyse at a higher concentration of sodium salt compared with normal RBCs.

Question 6

(6) The anemia seen in sickle cell disease is usually:

A. Microcytic, normochromic
B. Microcytic, hypochromic
C. Normocytic, normochromic
D. Normocytic, hypochromic

Answer 6

C. Normocytic, normochromic

Sickle cell disease is a chronic hemolytic anemia classified as a normocytic, normochromic anemia.

Question 7

(7) Which is the major Hgb found in the RBCs of patients with the sickle cell trait?

A. Hgb S
B. Hgb F
C. Hgb A2
D. Hgb A

Answer 7

D. Hgb A

The major Hgb in sickle cell trait is Hgb A, which constitutes 50% to 70% of the total. Hgb S comprises 20% to 40%, and Hgb A2 and Hgb F are present in normal amounts.

Question 8

(8) Select the amino acid substitution that is responsible for sickle cell anemia.

A. Lysine is substituted for glutamic acid at the sixth position of the α-chain
B. Valine is substituted for glutamic acid at the sixth position of the β-chain
C. Valine is substituted for glutamic acid at the sixth position of the α-chain
D. Glutamine is substituted for glutamic acid at the sixth position of the β-chain

Answer 8

B. Valine is substituted for glutamic acid at the sixth position of the β-chain

The structural mutation for Hgb S is the substitution of valine for glutamic acid at the sixth position of the β-chain. Because glutamic acid is negatively charged, this decreases its rate of migration toward the anode at pH 8.6.

Question 9

(9) All of the following are usually found in Hgb C disease except:

A. Hgb C crystals
B. Target cells
C. Lysine substituted for glutamic acid at the sixth position of the β–chain
D. Fast mobility of Hgb C at pH 8.6

Answer 9

D. Fast mobility of Hgb C at pH 8.6

Substitution of a positively charged amino acid for a negatively charged amino acid in Hgb C disease results in a slower electrophoretic mobility at pH 8.6.

Question 10

(10) Which of the following Hgbs migrates to the same position as Hgb A2 at pH 8.6?

A. Hgb H
B. Hgb F
C. Hgb C
D. Hgb S

Answer 10

C. Hgb C

At pH 8.6, several Hgbs migrate together. These include Hgb A2, Hgb C, Hgb E, Hgb 0Arab, and Hgb CHarlem. These are located nearest the cathode at pH 8.6.

Question 11

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

A. Hgb A: 40% Hgb S: 35% Hgb F: 5%
B. Hgb A: 60% Hgb S: 40% Hgb A2: 2%
C. Hgb A: 0% Hgb A2: 5% Hgb F: 95%
D. Hgb A: 80% Hgb S: 10% Hgb A2: 10%

Answer 11

B. Hgb A: 60% Hgb S: 40% Hgb A2: 2%

Electrophoresis at alkaline pH usually shows 50% to 70% Hgb A, 20% to 40% Hgb S, and normal levels of Hgb A2 in a patient with the sickle cell trait.

Question 12

(12) In which of the following conditions will autosplenectomy most likely occur?

A. Thalassemia major
B. Hgb C disease
C. Hgb SC disease
D. Sickle cell disease

Answer 12

D. Sickle cell disease

Autosplenectomy occurs in sickle cell anemia as a result of repeated infarcts to the spleen caused by an overwhelming sickling phenomenon.

Question 13

(13) Which of the following is most true of paroxysmal nocturnal hemoglobinuria (PNH)?

A. It is a rare acquired stem cell disorder that results in hemolysis
B. It is inherited as a sex-linked trait
C. It is inherited as an autosomal dominant trait
D. It is inherited as an autosomal recessive trait

Answer 13

A. It is a rare acquired stem cell disorder that results in hemolysis

PNH is a rare acquired stem cell disorder that results in abnormalities of the RBC membrane. This causes the RBCs to become highly sensitive to
complement-mediated hemolysis. Because this is a stem cell disorder, abnormalities are seen in leukocytes and PLTs, as well as in RBCs. PNH is characterized by recurrent, episodic intravascular hemolysis, hemoglobinuria, and venous thrombosis.

Question 14

(14) Hemolytic uremic syndrome (HUS) is characterized by all of the following except:

A. Hemorrhage
B. Thrombocytopenia
C. Hemoglobinuria
D. Reticulocytopenia

Answer 14

D. Reticulocytopenia

Hemolytic anemia of HUS is associated with reticulocytosis. The anemia seen in HUS is multifactorial, with characteristic thrombocytopenia, schistocytes, and polychromasia commensurate with the anemia

Question 15

(15) The autohemolysis test result is positive in all of the following conditions except:

A. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
B. HS
C. Pyruvate kinase (PK) deficiency
D. PNH

Answer 15

D. PNH

The autohemolysis test result is positive in G6PD and PK deficiencies and in HS but is normal in PNH because lysis in PNH requires sucrose to enhance complement binding. The addition of glucose, sucrose, or adenosine triphosphate (ATP) corrects autohemolysis of HS. Autohemolysis of PK can be corrected by ATP.

Question 16

(16) Which antibody is associated with paroxysmal cold hemoglobinuria (PCH)?

A. Anti-I
B. Anti-i
C. Anti-M
D. Anti-P

Answer 16

D. Anti-P

PCH is caused by the anti-P antibody, a cold autoantibody that binds to the patient’s RBCs at low temperatures and fixes complement. In the classic Donath–Landsteiner test, hemolysis is demonstrated in a sample placed at 4°C then warmed to 37°C.

Question 17

(17) All of the following are associated with intravascular hemolysis except:

A. Methemoglobinemia
B. Hemoglobinuria
C. Hemoglobinemia
D. Decreased haptoglobin

Answer 17

A. Methemoglobinemia

Methemoglobin occurs when iron is oxidized to the ferric state. Normally, iron is predominantly in the ferrous state in the Hgb that circulates. During intravascular hemolysis, the RBCs rupture, releasing Hgb directly into the bloodstream. Haptoglobin is a protein that binds to free Hgb. The increased free Hgb in intravascular hemolysis causes depletion of haptoglobin. As haptoglobin is depleted, unbound Hgb dimers appear in the plasma (hemoglobinemia) and are filtered through the kidneys and reabsorbed by the renal tubular cells. The renal tubular uptake capacity is approximately 5 g/day of filtered Hgb. Beyond this level, free Hgb appears in urine (hemoglobinuria). Hemoglobinuria is associated with hemoglobinemia.

Question 18

(18) Autoimmune hemolytic anemia (AIHA) is best characterized by which of the following?

A. Increased levels of plasma C3
B. Spherocytic RBCs
C. Decreased osmotic fragility
D. Decreased unconjugated bilirubin

Answer 18

B. Spherocytic RBCs

Spherocytes are characteristic of AIHA and cause increased osmotic fragility. In AIHAs, production of autoantibodies against one’s own RBCs causes hemolysis or phagocytic destruction of RBCs. A positive direct antiglobulin (DAT or Coombs’) test
identifies in vivo antibody-coated and complement coated RBCs. A positive DAT result distinguishes AIHA from other types of hemolytic anemia that produce spherocytes.

Question 19

(19) “Bite cells” are usually seen in patients with:

A. Rh null trait
B. Chronic granulomatous disease
C. G6PD deficiency
D. PK deficiency

Answer 19

C. G6PD deficiency

In patients with G6PD deficiency, the RBCs are unable to reduce nicotinamide adenine dinucleotide phosphate (NADP); consequently, Hgb is denatured, and Heinz bodies are formed. “Bite cells” appear in the peripheral circulation as a result of splenic pitting of Heinz bodies.

Question 20

(20) The morphological classification of anemias is based on which of the following?

A. Myeloid:erythroid (M:E) ratio
B. Prussian blue stain
C. RBC indices
D. Reticulocyte count

Answer 20

C. RBC indices

RBC indices classify the anemia morphologically. Anemias can be classified morphologically by using laboratory data; physiologically, based on the mechanism; and clinically, based on an assessment of symptoms.

Question 21

(21) Which of the following is a common finding in aplastic anemia?

A. A monoclonal disorder
B. Tumor infiltration
C. Peripheral blood pancytopenia
D. Defective deoxyribonucleic acid (DNA) synthesis

Answer 21

C. Peripheral blood pancytopenia

Aplastic anemia has many causes, such as chemical, drug, or radiation poisoning; congenital aplasia; and Fanconi syndrome. All result in depletion of hematopoietic precursors of all cell lines, leading to peripheral blood pancytopenia.

Question 22

(22) Congenital dyserythropoietic anemias (CDAs) are characterized by:

A. Bizarre multinucleated erythroblasts
B. Cytogenetic disorders
C. Megaloblastic erythropoiesis
D. An elevated M:E ratio

Answer 22

A. Bizarre multinucleated erythroblasts

There are four classifications of CDAs, each characterized by ineffective erythropoiesis, increased unconjugated bilirubin, and bizarre multinucleated erythroid precursors.

Question 23

(23) Microangiopathic hemolytic anemia is characterized by:

A. Target cells and Cabot rings
B. Toxic granulation and Döhle bodies
C. Pappenheimer bodies and basophilic stippling
D. Schistocytes and NRBCs

Answer 23

D. Schistocytes and NRBCs

Microangiopathic hemolytic anemia is a condition resulting from shear stress to the erythrocytes. Fibrin strands are laid down within the microcirculation, and RBCs become fragmented as they contact fibrin through the circulation process, forming schistocytes.

Question 24

(24) Which antibiotic(s) is (are) most often implicated in the development of aplastic
anemia?

A. Sulfonamides
B. Penicillin
C. Tetracycline
D. Chloramphenicol

Answer 24

D. Chloramphenicol

Chloramphenicol is the drug most often implicated in acquired aplastic anemia. About half the cases occur within 30 days after therapy, and about half are reversible. Penicillin, tetracycline, and sulfonamides have been implicated in a small number of cases.

Question 25

(25) Sickle cell disorders are:

A. Hereditary, intracorpuscular RBC defects
B. Hereditary, extracorpuscular RBC defects
C. Acquired, intracorpuscular RBC defects
D. Acquired, extracorpuscular RBC defects

Answer 25

A. Hereditary, intracorpuscular RBC defects

Sickle cell disorders are intracorpuscular RBC defects that are hereditary and result in defective Hgbs being produced. The gene for sickle cell can be inherited either homozygously or heterozygously.

Question 26

(26) Which of the following conditions may produce spherocytes in a peripheral blood
smear?

A. Pelger–Huët anomaly
B. Pernicious anemia
C. AIHA
D. Sideroblastic anemia

Answer 26

C. AIHA

Spherocytes are produced in AIHA. Spherocytes may be produced by one of three mechanisms. First, they are a natural morphological phase of normal RBC senescence. Second, they are produced when the cell surface:volume ratio is decreased, as seen in HS. And, third, they may be produced as a result of antibody coating of RBCs. As the antibody-coated RBCs travel through the spleen, the antibodies and portions of the RBC membrane are removed by macrophages. The membrane repairs itself; hence, the RBC’s morphology changes from a biconcave disk to a spherocyte.

Question 27

(27) A patient’s peripheral blood smear reveals numerous NRBCs, marked variation of RBC morphology, and pronounced polychromasia. In addition to decreased Hgb and decreased Hct values, what other CBC parameters may be anticipated?

A. Reduced PLTs
B. Increased MCHC
C. Increased MCV
D. Decreased RDW

Answer 27

C. Increased MCV

This patient’s abnormal peripheral blood smear indicates marked RBC regeneration, causing many reticulocytes to be released from bone marrow. Because reticulocytes are larger than mature RBCs, MCV will be slightly elevated.

Question 28

(28) What RBC inclusion may be seen in the peripheral blood smear from a patient postsplenectomy?

A. Toxic granulation
B. Howell–Jolly bodies
C. Malarial parasites
D. Siderotic granules

Answer 28

B. Howell–Jolly bodies

As a result of splenectomy, Howell–Jolly bodies may be seen in great numbers. One of the main functions of the spleen is pitting, which allows inclusions to be removed from the RBC without destroying the cell membrane.

Question 29

(29) Reticulocytosis usually indicates:

A. Response to inflammation
B. Neoplastic process
C. Aplastic anemia
D. RBC regeneration

Answer 29

D. RBC regeneration

Reticulocytes are polychromatophilic macrocytes, and the presence of reticulocytes indicates RBC regeneration. Bone marrow’s appropriate response to anemia is to deliver RBCs prematurely to the peripheral circulation. In this way, reticulocytes and possibly NRBCs may be seen in the peripheral blood smear.

Question 30

(30) Hereditary pyropoikilocytosis (HP) is an RBC membrane defect characterized by:

A. Increased pencil-shaped cells
B. Increased oval macrocytes
C. Misshapen budding fragmented cells
D. Bite cells

Answer 30

C. Misshapen budding fragmented cells

HP is a membrane defect characterized by a spectrin abnormality and thermal instability. MCV is decreased, and RBCs appear to be budding and fragmented.