Clinical Hematology And Coagulation

Front 1

Which test would confirm the diagnosis of cold agglutinin disease?
a. Hemoglobin electrophoresis
b. Osmotic fragility
c. Direct antiglobulin test
d. Heat stability test
e. Search for Howell-Jolly bodies on blood smear

Back 1

c. Patients with
cold agglutinin disease
commonly demonstrate a cold reactive IgM autoantibody, agglutination on peripheral smear, and a
direct antiglobulin test that is positive for complement. Cold agglutinin disease comprises 16% to 32% of all autoimmune hemolytic anemias and is not associated with altered osmotic fragility, underlying hemoglobinopathy, or unstable hemoglobin. Howell-Jolly bodies are a sign of splenic dysfunction and are not seen in cold agglutinin disease.

Front 2

CD30 (Ki-1) is sometimes or always positive in all of the following lymphoproliferative disorders EXCEPT:
a. Histiocytic sarcoma
b. Lymphomatoid papulosis
c. Classical Hodgkin lymphoma
d. Anaplastic large cell lymphoma
e. Adult T-cell leukemia/lymphoma

Back 2

a.

Front 3

Which test would confirm the diagnosis of hereditary spherocytosis?
a. Hemoglobin electrophoresis
b. Osmotic fragility
c. Direct antiglobin test
d. Heat stability test
e. Search for Howell-Jolly bodies on blood smear

Back 3

b. Patients with hereditary spherocytosis often demonstrate a compensated hemolytic anemia with increased reticulocytosis and increased indirect bilirubin. These patients may have an increased MCHC and increased number of spherocytes on peripheral smear.
Osmotic fragility testing
demonstrates osmotic fragility at higher sodium chloride concentrations upon immediate incubation of sample compared with controls. This difference in osmotic fragility is more marked upon 24-hour incubation.

Front 4

Which of the following is NOT a sign of extravascular hemolysis?
a. Anemia
b. Increase in indirect bilirubin
c. Increase in urobilinogen
d. Increase in fecal stercobilinogen
e. Increase in plasma hemoglobin

Back 4

e. Increased plasma hemoglobin
is commonly seen in intravascular hemolysis.

Front 5

Which of the following is NOT a sign of acute intravascular hemolysis?
a. Increase in plasma hemoglobin
b. Decrease or disappearance of haptoglobin
c. Presence of methemoglobin
d. Appearance of hemoglobinuria
e. Increase in urobilinogen

Back 5

e. Urobilinogen results from intrahepatic circulation of the breakdown products of bilirubin in the gut that is excreted by the kidneys and usually occurs as a result of chronic hemolysis. When
intravascular hemolysis occurs, hemoglobin is released from red blood cells resulting in elevated plasma hemoglobin. Hemoglobinuria results when the hemoglobin (Hb) released into the plasma exceeds the binding capacity of plasma-binding proteins. Unbound Hb is reabsorbed into renal tubular cells, where iron is converted to hemosiderin. Hemosiderin appears in the urine when the renal tubular cells slough off and can be seen with chronic intravascular hemolysis. Elevated plasma hemoglobin causes marked decrease of haptoglobin because of the binding of hemoglobin to haptoglobin and subsequent rapid clearance and glomerular filtration and deposition of the hemoglobin in the proximal tubules. Plasma methemalbumin increases because there is increased release of oxidized heme from unbound plasma hemoglobin and binding to albumin.

Front 6

Which of the following is NOT commonly seen with pyruvate kinase deficiency?
a. Most commonly seen in frequency after G6PD deficiency
b. Frequent in Europeans
c. Autosomal recessive
d. Osmotic fragility is normal
e. Chronic, spherocytic hemolytic anemia

Back 6

e. Pyruvate kinase deficiency
is associated with chronic, nonspherocytic hemolytic anemia.

Front 7

Excluding flow cytometry, which of the following is the best test for paroxysmal nocturnal hemoglobinuria?
a. Sugar water test
b. Kinetic studies with 51Cr-labeled red cells
c. Ham test
d. Decreased red cell acetylcholinesterase
e. Direct antiglobin test

Back 7

c. Paroxysmal nocturnal hemoglobinuria
(PNH) is suspected in patients who have unexplained normocytic anemia with intravascular hemolysis, especially if leukopenia or thrombocytopenia is present. The sugarwater test, which relies on the enhanced hemolysis of C3-dependent systems in isotonic solution of low ionic strength, is usually the first test performed and demonstrates high sensitivity. However, because this test is not specific for PNH, positive results require confirmation by flow cytometric testing or, alternatively, the acid hemolysis test (Ham test),
which demonstrates hemolysis upon acidification of a blood specimen in the presence of a fresh source of complement.

Front 8

Which of the following is NOT a cause or characteristic of methemoglobinemia?
a. Hemoglobin M
b. Deficiency of NADH reductase
c. Neonatal ingestion of nitrates
d. Cyanosis
e. Dark- or brown-colored plasma

Back 8

b. Methemoglobinemia
is a condition in which the iron within hemoglobin is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, resulting in the inability to transport oxygen and carbon dioxide. Clinically, this condition causes cyanosis and often results in dark or brown-colored plasma. In children, methemoglobinemia usually results either from exposure to oxidizing substances (such as nitrates or nitrites, aniline dyes, or medications) or is the result of inborn errors of metabolism (such as glucose-6-phosphate dehydrogenase [G6PD] deficiency and cytochrome b5 oxidase deficiency) or severe acidosis, which causes an acquired dysfunction of cytochrome b5 oxidase.

Front 9

Which of the following is NOT characteristic of alpha thalassemia minor?
a. 5% to 10% Hb Bart at birth
b. Inheritance of homozygous or heterozygous genotype
c. Microcytosis
d. Elevated RBC count
e. Elevated Hb A2

Back 9

e. Elevated Hb A2
is commonly associated with beta thalassemia trait. All the other answers are seen with alpha thalassemia minor.

Front 10

What is the earliest marker of B-cell lineage?
a. cCD22
b. CD10
c. CD19
d. CD38
e. CD79a

Back 10

a. The earliest B-cell precursors can be identified by cCD22. This is followed by the appearance of CD19 and CD10. The subsequent maturation and differentiation of the B-cell lineage is characterized by gradual decrease in CD10 together with gradual gain in CD20. CD38 is a lineage nonspecific marker of hematopoietic cells.

Front 11

Hemoglobin H disease is NOT associated with:
a. Normal Hb F level
b. Tetramer of gamma chains at birth
c. Hemolytic anemia
d. <5% Hb Bart at birth
e. Splenomegaly

Back 11

d. Hemoglobin H disease is associated with 20% to 40% Hb Bart at birth; however, by 1 year of age, there is only a trace of Hb Bart present.

Front 12

Hemoglobin Lepore is NOT associated with:
a. Elevated Hb A2
b. Crossover between β and οgenes
c. Thalassemic indices
d. Elevated Hb F
e. Difficulty in detection early in life

Back 12

a. Because hemoglobin Lepore is a result of an event that results in a crossover (knockout) of one of the ο and genes, the expression of the hemoglobin A2 is decreased and not increased. Because the hemoglobin Lepore molecule is not well expressed in cells, it is difficult to detect early in life but does result in a microcytic anemia similar to beta thalassemia.

Front 13

Elevated hemoglobin F can be seen in all of the following EXCEPT:
a. Pregnancy (first trimester)
b. Juvenile myelomonocytic leukemia
c. Myelofibrosis
d. Trisomy 21
e. Hemoglobin H disease

Back 13

e.Hemoglobin F is a tetramer composed of two alpha chains and two gamma chains. Hemoglobin H disease involves a deletion of three of four alpha globin genes. The other diagnoses are not associated with a deletion of alpha globin genes. Elevated hemoglobin F is also seen in β thalassemia, sickle cell anemia, chronic myelomonocytic leukemia, and οβ thalassemia.

Front 14

What ratio of Hb A to Hb S is seen in adult sickle cell trait patients?
a. 30:70
b. 40:60
c. 50:50
d. 60:40
e. 70:30

Back 14

d.These numbers are important to remember because a ratio other than 60:40 may represent a transfused sickle cell disease patient or sickle beta (+) thalassemia.

Front 15

Causes of elevated Hb A2 are seen in:
a. α; Thalassemia minor
b. οβ Thalassemia trait
c. Iron deficiency
d. Hereditary persistence of fetal hemoglobin
e. βThalassemia trait

Back 15

e.

Front 16

Which of the following RBC abnormalities is NOT seen with myelofibrosis?
a Anisocytosis
b. Poikilocytosis
c. Macrocytosis
d. Schistocytes
e. Acanthocytes

Back 16

e.The RBC morphology in myelofibrosis includes all of the above except acanthocytes and also typically demonstrates teardrop cells. Acanthocytes are very rarely seen in normal peripheral smears and when seen in increased numbers, the diagnosis of abetalipoproteinemia should be entertained.

Front 17

Which of the following RBC abnormalities is NOT seen with unstable hemoglobin?
a. Heinz bodies
b. Polychromasia
c. Anisocytosis
d. Microcytosis
e. Poikilocytosis

Back 17

d.Unstable hemoglobins are associated with increased anisocytosis and poikilocytosis on peripheral smear. Because a hemolytic anemia is often involved, polychromasia (reticulocytosis) is often present. The Heinz body test is usually positive. Other tests that are used to evaluate the presence of an unstable hemoglobin include the isopropanol stability test and the heat stability test.

Front 18

Which of the following is NOT seen with impaired hemoglobin synthesis?
a. Target cells
b. Anisocytosis
c. Schistocytes
d. Microcytosis
e. Basophilic stippling

Back 18

c. Schistocytes are usually associated with microangiopathic hemolytic anemia.

Front 19

Which RBC feature is characteristically seen with abetalipoproteinemia?
a. Acanthocytes
b. Polychromasia
c. Anisocytosis
d. Target cells
e. Poikilocytosis

Back 19

a.

Front 20

All of the following flow cytometry markers are expressed by hairy cell leukemia cells EXCEPT:
a. CD25
b. CD5
c. CD19
d. CD20
e. CD11c

Back 20

b. Hairy cell leukemia cells have a specific phenotype that makes the detection of leukemic cells easier. Cells are positive for mature B-cell markers such as CD19, CD20, and CD22. CD25 and CD11c are also positive. They also show bright CD45 expression and expression of surface immunoglobulins. CD5 is typically negative.

Front 21

The megakaryoblast displays which of the following surface marker reactivity?
a. CD34+, CD33-, HLA-DR+, CD41+, CD61+
b. CD34+, CD33+, HLA-DR+, CD42+, CD36+
c. CD34+, CD33+, HLA-DR-, CD42+, CD36+
d. CD34-, CD33-, HLA-DR+, CD42+, CD36+
e. CD34+, CD33-, HLA-DR-, CD42-, CD61-

Back 21

c.

Front 22

The promonocyte displays which of the following surface marker reactivity?
a. CD13+, CD33+, CD34+, HLD+DR+
b. CD13+, CD33+, CD11b+, CD14+, HLA+DR+
c. CD13+, CD33+, CD11b+, CD14+, HLA+DR-
d. CD13+, CD33+, CD11b+, CD14+, HLA+DR-
e. CD13+, CD33+, CD11b-, CD14-, HLA+DR-

Back 22

b. These markers are also seen on monocytes. Choice “a” could describe the phenotype of either a monoblast or myeloblast, while “c”, “d”, and “e” could describe a myelocytic, metamyelocyte/neutrophil, and promyelocyte phenotype, respectively.

Front 23

Characteristics of acute promyelocytic leukemia include all the following EXCEPT:
a. Bundles of Auer rods
b. Intense MPO activity
c. CD13+, CD33+, HLA-DR+, CD34- phenotype
d. DIC
e. t(15:17)(p21;q11)

Back 23

c. The cells seen in acute promyelocytic leukemia are characteristically HLA-DR negative.

Front 24

Reactive megakaryocytic hyperplasia can be distinguished from neoplastic megakaryocytic hyperplasia by all of the following EXCEPT:
a. Peripheral basophilia
b. Leukoerythroblastic peripheral blood pattern
c. Bone marrow fibrosis
d. Packed bone marrow (90% cellularity)
e. Spontaneous colony formation of megakaryocytic and/or erythroid precursors.

Back 24

e. Most reactive disorders have a platelet count ×1000 × 109/L and a normocellular marrow. Occasionally some cases will have a more severe thrombocytosis and a hypercellular marrow simulating a myeloproliferative disorder. Peripheral basophilia, bone marrow fibrosis, extremely high cellularity (90% cellularity), and a leukoerythroblastic peripheral blood smear are features which favor a neoplastic megakaryocytic hyperplasia. Essential thrombocytosis (ET, also known as essential thrombocythemia) is a rare chronic myeloproliferative blood disorder characterized by the overproduction of platelets by megakaryocytes in the bone marrow in the absence of an alternative cause. In some cases this disorder may be progressive, and rarely may evolve into acute myeloid leukemia or myelofibrosis. Other supporting features for ET included enlarged hyperlobulated megakaryocytes, however, basophilia and bone marrow fibrosis are not typical features of ET. Appropriate clinical findings are also required for diagnosis. Using in vitro culture of hematopoietic precursors, approximately 75% of patients with ET will demonstrate spontaneous megakaryocytic and/or erythroid colony formation with the need for added growth factors. This is almost never seen in patients with reactive thrombocytosis.

Front 25

The 5q- syndrome associated with MDS has all of the following features in an elderly female EXCEPT:
a. Moderately increased platelet counts generally greater than 1000 × 109/L
b. Regular RBC transfusions
c. High risk to progression to AML
d. Hypolobulated megakaryocytes
e. Macrocytic anemia

Back 25

c. The 5q- syndrome associated with MDS is primarily a cytogenetic and clinical entity with a favorable prognosis. The risk to progression to AML, concomitant infection, thrombosis, and anemia are low. In an elderly female the presence of elevated platelet counts (generally >1000 × 109/L), hypolobulated megakaryocytes, and a macrocytic anemia suggest the 5q- syndrome. However, it should be noted that none of the above features are specific to the 5q- syndrome.

Front 26

Hematogones can be recognized using flow cytometry by all the following EXCEPT:
a. Low forward scatter
b. Low side scatter
c. Heterogeneous CD20 intensity
d. Strong CD34 expression
e. CD10 expression that is often less bright than that expressed by ALL blasts.

Back 26

d.

Front 27

The following is true of all natural killer cells EXCEPT:
a. They comprise 10% to 15% of peripheral blood lymphocytes.
b. Majority have a morphology of large granular lymphocytes.
c. Maturation is thymic independent.
d. They are CD2+, CD7+, CD8+, CD16+, and CD56+.
e. They can be distinguished using paraffin-resistant polyclonal CD3 antibodies.

Back 27

e.NK cells are surface CD3ε; however, these cells express CD3ε chains in the cytoplasm and therefore canhemolysis not be distinguished on paraffin sections using paraffin resistant polyclonal anti-CD3 antibodies.

Front 28

All of the following are true of chronic myeloid leukemia EXCEPT:
a. WBC count of at least 50 × 109/L
b. Absolute basophilia greater than 0.2 × 109/L
c. Marked granulocytosis with predominance of promyelocytes
d. bcr-abl fusion
e. NRBCs are present.

Back 28

c. A predominance of myelocytes is seen in this disorder. All stages of the myeloid series are seen with peaks in the neutrophil and myelocytes stages.

Front 29

Pseudo Pelger-Huet cells can be seen in all of the following disorders EXCEPT:
a. Iron deficiency
b. Infectious/inflammatory processes
c. Toxic intestinal disorders
d. Chronic myeloid leukemia
e. Myelodysplastic syndrome

Back 29

a. Pseudo Pelger-Hüet cells
can be seen in a variety of conditions, including trisomy 18, myxedema associated with panhypopituitarism, vitamin B12 and folate deficiency, multiple myeloma, malaria, muscular dystrophy, and leukemoid reactions secondary to bone metastases. This condition should be distinguished from the clinically innocuous Pelger-Hüet anomaly. Iron deficiency
can be associated with thrombocytosis and often presents with a hypochromic microcytic anemia.

Front 30

Characteristics of mature T cells include all of the following EXCEPT:
a. CD3+, CD4+ cells account for approximately 70% to 80% of peripheral blood T cells.
b. CD3+, CD8+ cells account for approximately 20% to 35% of peripheral blood T cells.
c. A subset of CD8+ cells expresses one or more NKassociated antigens, usually CD16 and CD57.
d. Populations of CD4+/CD8+ and CD4-/CD8-cells are seen in very low percentages (approximately 1% to 2%).
e. After chemotherapy, an increase of CD4-/CD8-cells in the 10% to 20% range can be seen.

Back 30

a. CD3+, CD4+
cells account for approximately 55% to 65% of peripheral blood T cells.