ASCP Harr Review
B Auer rods are not seen characteristically in lymphoblasts. They may be seen in myeloblasts, promyelocytes, and monoblasts.
1.
B The osmotic fragility is decreased because numerous target cells are present and have increased surface volume in thalassemia major patients.
1.
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.
1.
C Occasionally patients with infectious mononucleosis develop a potent cold agglutinin with anti-I specificity. This cold autoantibody can cause strong hemolysis and a hemolytic anemia.
1.
D Megaloblastic macrocytic anemia is normochromic because there is no defect in the Hgb synthesis. These anemias comprise a group of asynchronized anemias characterized by defective nuclear maturation due to defective deoxyribonucleic acid (DNA) synthesis. This abnormality accounts for the megaloblastic features in the bone marrow and the macrocytosis in the peripheral blood.
1.
B The patient will have an increased MCV. One of the causes of a macrocytic anemia that is not megaloblastic is an increased reticulocyte count, here noted as increased polychromasia. Reticulocytes are polychromatic macrocytes; therefore, the MCV is slightly increased.
10.
C At pH 8.6, several hemoglobins migrate together. These include Hgb A2, Hgb C, Hgb E, Hgb OArab, and Hgb CHarlem. These are located nearest the cathode at pH 8.6.
10.
C The indices will provide a morphological classification of this anemia. The MCV is 75 fL (reference range 80-100 fL), the MCH is 20.0 pg (reference range 27-31 pg), and the MCHC is 26.6% (reference range 32%-36%). Therefore, the anemia is microcytic hypochromic.
10.
D If both the heterophile antibody test and the EBV-IgM tests are negative in a patient with reactive lymphocytosis and a suspected viral infection, the serum should be analyzed for IgM antibodies to CMV. CMV belongs to the herpes virus family and is endemic worldwide. CMV infection is the most common cause of heterophile-negative infectious mononucleosis.
10.
A The biochemical products of the respiratory burst that are involved with neutrophil particle ingestion during phagocytosis are hydrogen peroxide and superoxide anion. The activated neutrophil discharges the enzyme NADPH oxidase into the phagolysosome, where it converts O2 to superoxide anion (O2-), which is then reduced to hydrogen peroxide (H2O2).
11.
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.
11.
C Hgb A is part of the normal complement of adult 2 Hgb. This Hgb is elevated in β-thalassemia minor because the individual with this condition has only one normal β-gene; consequently, there is a slight elevation of Hgb A2 and Hgb F.
11.
B Thirty to fifty percent of the individuals with the anemia of chronic inflammation demonstrate a microcytic hypochromic blood picture with decreased serum iron. Serum iron is decreased because it is unable to escape from the RE cells to be delivered to the nucleated red cells in the bone marrow.
12.
D Autosplenectomy occurs in sickle cell anemia as a result of repeated infarcts to the spleen caused by the overwhelming sickling phenomenon.
12.
D Both reactive lymphocytes and blasts may have basophilic cytoplasm, a high N:C ratio, and the presence of prominent nucleoli. Blasts, however, have an extremely fine nuclear chromatin staining pattern as viewed on a Wright's-Giemsa's—stained smear.
12.
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.
13.
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.
14.
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.
15.
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.
16.
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.
17.
B Spherocytes are characteristic of autoimmune hemolytic anemia and 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.
18.
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.
19.
B The spleen is the supreme filter of the body, pitting imperfections from the erythrocyte without destroying the integrity of the membrane.
2.
C HIV infection brings about several hematological abnormalities seen on peripheral smear examination; most patients demonstrate reactive lymphocytes and have granulocytopenia.
2.
C In iron deficiency anemia (IDA), there is an increase in TIBC and in RBC protoporphyrin. The serum iron and ferritin levels are decreased. IDA is characterized by a microcytic hypochromic anemia.
2.
D Pernicious anemia is caused by a lack of intrinsic factor, which prevents vitamin B12 absorption.
2.
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.
20.
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.
21.
A There are four classifications of CDAs, each characterized by ineffective erythropoiesis, increased unconjugated bilirubin, and bizarre multinucleated erythroid precursors.
22.
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.
23.
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.
24.
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.
25.
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.
26.
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.
27.
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.
28.
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.
29.
A Döhle bodies are RNA-rich areas within polymorphonuclear neutrophils (PMNs) that are oval and light blue in color. Although often associated with infectious states, they are seen in a wide range of conditions and toxic reactions, including hemolytic and pernicious anemias, chronic granulocytic leukemia, and therapy with antineoplastic drugs. The other inclusions are associated with erythrocytes.
3.
B Megaloblastic anemias are associated with an ineffective erythropoiesis and therefore a decrease in the reticulocyte count.
3.
D In iron deficiency anemia, the serum iron and ferritin levels are decreased and the total iron-binding capacity and RBC protoporphyrin are increased. In chronic disease, serum iron and TIBC are both decreased because the iron is trapped in reticuloendothelial (RE) cells, and is unavailable to the red cells for hemoglobin production.
3.
D Spherocytes lose their deformability owing to the defect in spectrin, a membrane protein, and are therefore prone to splenic sequestration and hemolysis.
3.
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.
30.
B Administration of folic acid to a patient with vitamin B12 deficiency will improve the hematological abnormalities; however, the neurological problems will continue. This helps to confirm the correct diagnosis of vitamin B12 deficiency.
4.
B Iron deficiency anemia and thalassemia are both classified as microcytic, hypochromic anemias. Iron deficiency anemia is caused by defective heme synthesis; whereas thalassemia is caused by decreased globin chain synthesis.
4.
B Myeloperoxidase, lysozyme, and acid phosphatase are enzymes that are contained in the primary granules of neutrophils. The contents of secondary and tertiary granules include lactoferrin, collagenase, NADPH oxidase, and alkaline phosphatase.
4.
C Classic features of intravascular hemolysis such as hemoglo binemia, hemoglobinuria, or hemosiderinuria do not occur in hereditary spherocytosis. The hemolysis seen in hereditary spherocytosis is an extravascular rather than an intravascular process.
4.
A Iron deficiency anemia is characterized by decreased plasma iron, increased TIBC, decreased % saturation, and microcytic, hypochromic anemia. Iron deficiency occurs in three phases: iron depletion, iron-deficient erythropoiesis, and iron deficiency anemia.
5.
D Ineffective erythropoiesis is caused by destruction of erythroid precursor cells prior to their release from the bone marrow. Pernicious anemia results from defective DNA synthesis; it is suggested that the asynchronous development of red cells renders them more liable to intramedullary destruction.
5.
D Spherocytic cells have decreased tolerance to swelling and, therefore, hemolyze at a higher concentration of sodium salt compared with normal red cells.
5.
D The mean relative lymphocyte percentage for a 1-year-old child is 61% compared to the mean lymphocyte percentage of 35% for an adult.
5.
B Neutrophil changes associated with infection may include neutrophilia, shift to the left, toxic granulation, Döhle bodies, and vacuolization. Pelgeroid hyposegmentation is noted in neutrophils from individuals with the congenital Pelger-Huët anomaly and as an acquired anomaly induced by drug ingestion or secondary to conditions such as leukemia.
6.
C Sickle cell disease is a chronic hemolytic anemia classified as a normocytic, normochromic anemia.
6.
D Ferritin enters the serum from all ferritin-producing tissues, and therefore is considered to be a good indicator of body storage iron. Because iron stores must be depleted before anemia develops, low serum ferritin levels precede the fall in serum iron associated with iron deficiency anemia.
6.
D Patients with pernicious anemia demonstrate a pancytopenia with low WBC, PLT, and RBC counts. Because this is a megaloblastic process and a DNA maturation defect, all cell lines are affected. In the bone marrow, this results in abnormally large precursor cells, maturation asynchrony, hyperplasia of all cell lines, and a low M:E ratio.
6.
A Neutropenia is defined as an absolute decrease in the number of circulating neutrophils. This condition is present in patients having neutrophil counts of less than 1.5 × 10^9/L.
7.
B Patients with obstructive liver disease may have red blood cells that have an increased tendency toward the deposition of lipid on the surface of the red cell. Consequently, the red cells are larger or more macrocytic than normal red cells.
7.
D Sideroblastic anemia has a decreased red cell protoporphyrin. The defect in sideroblastic anemia involves ineffective erythropoiesis. The failure to produce RBC protoporphyrin occurs because the nonheme iron is trapped in the mitochondria and is unavailable to be recycled.
7.
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.
7.
B Chédiak-Higashi syndrome is a disorder of neutrophil phagocytic dysfunction caused by depressed chemotaxis and delayed degranulation. The degranulation disturbance is attributed to interference from the giant lysosomal granules characteristic of this disorder.
8.
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.
8.
C In thalassemia major, there is little or no production of the β-chain, resulting in severely depressed or no synthesis of Hgb A. Severe anemia is seen, along with skeletal abnormalities and marked splenomegaly. The patient is usually supported with transfusion therapy.
8.
C Macrocytes in true megaloblastic conditions are oval macrocytes as opposed to the round macrocytes that are usually seen in alcoholism and obstructive liver disease.
8.
C Pelger-Huët anomaly is a benign familial condition reported in 1 out of 6,000 individuals. Care must be taken to differentiate Pelger-Huët cells from the numerous band neutrophils and metamyelocytes that may be observed during severe infection or a shift-to-the-left of immaturity in granulocyte stages.
9.
C The red cell indices in a patient with megaloblastic anemia are macrocytic and normochromic. The macrocytosis is prominent, with an MCV ranging from 100 to 130 fL.
9.
D Patients with thalassemia major are unable to synthesize the β-chain; hence, little or no Hgb A is produced. However, γ-chains continue to be synthesized and lead to variable elevations of Hgb F in these patients.
9.
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.
9.
