1.2 Hematology: Normocytic and Normochromic Anemias

Hypersplenism is characterized by:

A. Polycythemia

B. Pancytosis

C. Leukopenia

D. Myelodysplasia

C. Leukopenia

C 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.

Which of the following organs is responsible for the "pitting process" for RBCs?

A. Liver

B. Spleen

C. Kidney

D. Lymph nodes

B. Spleen

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

Spherocytes differ from normal red cells in all of the following except:

A. Decreased surface to volume

B. No central pallor

C. Decreased resistance to hypotonic saline

D. Increased deformability

D. Increased deformability

D Spherocytes lose their deformability owing to the defect in spectrin, a membrane protein, and are therefore prone to splenic sequestration and hemolysis.

Which of the following is not associated with hereditary spherocytosis?

A. Increased osmotic fragility

B. An MCHC greater than 36%

C. Intravascular hemolysis

D. Extravascular hemolysis

C. Intravascular hemolysis

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

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

A. Iron deficiency anemia

B. Hereditary elliptocytosis

C. Hereditary stomatocytosis

D. Hereditary spherocytosis

D. Hereditary spherocytosis

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

The anemia seen in sickle cell disease is usually:

A. Microcytic, normochromic

B. Microcytic, hypochromic

C. Normocytic, normochromic

D. Normocytic, hypochromic

C. Normocytic, normochromic

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

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

A. Hgb S

B. Hgb F

C. Hgb A2

D. Hgb A

D. Hgb A

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

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

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

B 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.

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

D. Fast mobility of Hgb C at pH 8.6

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

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

A. Hgb H

B. Hgb F

C. Hgb C

D. Hgb S

C. Hgb C

C At pH 8.6, several hemoglobins 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.

Which of the following electrophoretic results is consistent with a diagnosis of 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%

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

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

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

A. Talassemia major

B. Hgb C disease

C. Hgb SC disease

D. Sickle cell disease

D. Sickle cell disease

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

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

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

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

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

A. Hemorrhage

B. Trombocytopenia

C. Hemoglobinuria

D. Reticulocytopenia

D. Reticulocytopenia

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

An autohemolysis test is positive in all the following conditions except:

A. Glucose-6-phosphate dehydrogenase (G6PD)

deficiency

B. Hereditary spherocytosis (HS)

C. Pyruvate kinase (PK) deficiency

D. Paroxysmal nocturnal hemoglobinuria (PNH)

D. Paroxysmal nocturnal hemoglobinuria (PNH)

D The autohemolysis test 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 the autohemolysis of HS. Autohemolysis of PK can be corrected by ATP.

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

A. Anti-I

B. Anti-i

C. Anti-M

D. Anti-P

D. Anti-P

D 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 that is then warmed to 37°C

All of the following are associated with intravascular hemolysis except:

A. Methemoglobinemia

B. Hemoglobinuria

C. Hemoglobinemia

D. Decreased haptoglobin

A. Methemoglobinemia

A Methemoglobin occurs when iron is oxidized to the ferric state. Normally, iron is predominantly in the ferrous state in the hemoglobin that circulates. During intravascular hemolysis, the red cells rupture, releasing hemoglobin 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 hemoglobin 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 per day of filtered hemoglobin. Beyond this level, free hemoglobin appears in the urine (hemoglobinuria). Hemoglobinuria is associated

with hemoglobinemia.

Autoimmune hemolytic anemia is best characterized by which of the following?

A. Increased levels of plasma C3

B. Spherocytic red cells

C. Decreased osmotic fragility

D. Decreased unconjugated bilirubin

B. Spherocytic red cells

B Spherocytes are characteristic of autoimmune

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

"Bite cells" are usually seen in patients with:

A. Rh null trait

B. Chronic granulomatous disease

C. G6PD deficiency

D. PK deficiency

C. G6PD deficiency

C In patients with G6PD deficiency, the red cells are unable to reduce nicotinamide adenine dinucleotide phosphate (NADP) to NADPH; 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.

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

A. M:E (myeloid:erythroid) ratio

B. Prussian blue stain

C. RBC indices

D. Reticulocyte count

C. RBC indices

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

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

A. A monoclonal disorder

B. Tumor infiltration

C. Peripheral blood pancytopenia

D. Defective DNA synthesis

C. Peripheral blood pancytopenia

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

Congenital dyserythropoietic anemias (CDAs) are characterized by:

A. Bizarre multinucleated erythroblasts

B. Cytogenetic disorders

C. Megaloblastic erythropoiesis

D. An elevated M:E ratio

A. Bizarre multinucleated erythroblasts

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

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 nucleated RBCs

D. Schistocytes and nucleated RBCs

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

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

A. Sulfonamides

B. Penicillin

C. Tetracycline

D. Chloramphenicol

D. Chloramphenicol

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

sulfonamides have been implicated in a small number of cases.

Sickle cell disorders are:

A. Hereditary, intracorpuscular RBC defects

B. Hereditary, extracorpuscular RBC defects

C. Acquired, intracorpuscular RBC defects

D. Acquired, extracorpuscular RBC defects

A. Hereditary, intracorpuscular RBC defects

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

Which of the following conditions may produce spherocytes in a peripheral smear?

A. Pelger-Huët anomaly

B. Pernicious anemia

C. Autoimmune hemolytic anemia

D. Sideroblastic anemia

C. Autoimmune hemolytic anemia

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

A patient's peripheral smear reveals numerous NRBCs, marked variation of red cell morphology, and pronounced polychromasia. In addition to a

decreased Hgb and decreased Hct values, what other CBC parameters may be anticipated?

A. Reduced platelets

B. Increased MCHC

C. Increased MCV

D. Decreased red-cell distribution width (RDW)

C. Increased MCV

C This patient's abnormal peripheral smear indicates marked red cell regeneration, causing many reticulocytes to be released from the marrow. Because reticulocytes are larger than mature RBCs, the MCV will be slightly elevated

What red cell inclusion may be seen in the peripheral blood smear of a patient postsplenectomy?

A. Toxic granulation

B. Howell-Jolly bodies

C. Malarial parasites

D. Siderotic granules

B. Howell-Jolly bodies

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

Reticulocytosis usually indicates:

A. Response to inflammation

B. Neoplastic process

C. Aplastic anemia

D. Red cell regeneration

D. Red cell regeneration

D Reticulocytes are polychromatophilic macrocytes, and the presence of reticulocytes indicates red cell regeneration. The bone marrow's appropriate response to anemia is to deliver red cells prematurely to the peripheral circulation. In this way, reticulocytes and possibly nucleated red cells may be seen in the peripheral smear

Hereditary pyropoikilocytosis (HP) is a red cell membrane defect characterized by:

A. Increased pencil-shaped cells

B. Increased oval macrocytes

C. Misshapen budding fragmented cells

D. Bite cells

C. Misshapen budding fragmented cells

C HP is a membrane defect characterized by a spectrin abnormality and thermal instability. The MCV is decreased and the red cells appear to be budding and fragmented.