A.

Erythrocyte

A. The need for oxygen delivery to developing tissues results in the production of erythrocytes before other blood cells.
Erythropoiesis commences in the yolk sac as early as the fourteenth day of embryonic development. These primitive red
cells produce embryonic hemoglobins that temporarily serve oxygen needs of the fetus. Myelopoietic and lymphopoietic
activities begin when the liver and spleen become sites of production at 6-9 weeks of gestation; however, erythropoiesis
still predominates. At this time, the red cells produce hemoglobin F, which is the chief oxygen carrier during fetal life.
What is the first type of cell produced by the developing embryo?

A. Erythrocyte
B. Granulocyte
C. Lymphocyte
D. Thrombocyte
C. 50%

C. In the infant, there is an increased demand for blood formation because of the rate of growth. At birth, all bone marrow
cavities are filled with hematopoietic tissue (active red marrow). As the growth rate slows, there is less need for active
marrow. Fatty infiltration of the marrow becomes noticeable at about 4 years of age as cell production diminishes within
the shafts of the long bones and is filled with yellow inactive tissue. Fat comprises 50% of the total marrow space in the
adult. Except for lymphopoiesis, hematopoiesis is confined to the flat bones and pelvic area by the age of 25 years.
What percentage of tissue located in the bone marrow cavities of adults is fat?

A. 10%
B. 25%
C. 50%
D. 75%
C. Express the stem cell marker CD 13

C. Hematopoietic stem cells can make copies of themselves to maintain the stem cell pool and possess the ability to
generate cells of all lineages (pluripotential). These stem cells give rise to multipotential myeloid and lymphoid progenitor
cells, which ultimately produce progenitor cells that are restricted to a specific cell lineage. With appropriate cytokine
stimulus, the committed progenitor cells undergo proliferation to recognizable precursors that produce an amplified
number of mature end-stage cells. Stem cells and progenitor cells cannot be morphologically distinguished (look similar to
small lymphocytes) but can be identified phenotypically by markers such as the stem cell marker CD34. CD34 expression
is lost as antigens for a specific cell lineage are expressed. CD 13 is a marker expressed by
myeloid precursors.
Which of the following is not characteristic of pluripotent hematopoietic stem cells?

A. Possess self-renewal ability

B. Produce progenitor cells committed to a single cell lineage
C. Express the stem cell marker CD 13
D. Are morphologically unrecognizable
D. Posterior iliac crest, sternum

D. Unlike the infant, in which all bone marrow is capable of forming blood cells, the active marrow in an adult is confined
to the flat bones of the skeleton such as the sternum and posterior iliac crest. Although the spinous processes of the
vertebrae contain active marrow, these sites are rarely used for aspiration in adults because of the danger of damage to
the spinal cord. Sternal puncture also presents a possibility of serious damage to underlying structures, but this site may
be used because of easy accessibility or if the aspirate is a "dry tap" in the iliac crest. To obtain both a bone marrow
aspirate and core biopsy, most marrow specimens are taken from the posterior iliac crest. The anterior iliac crest may
occasionally be used in adults and sometimes the tibia in children less than 2 years of age
4. In an adult, what are the two best areas for obtaining active bone marrow by aspiration?

A. Vertebra, tibia
B. Sternum, vertebra
C. Anterior iliac crest, tibia
D. Posterior iliac crest, sternum
C. 4:1

C. The ratio between all granulocytes and their precursors and all nucleated red cell precursors represents the myeloid-to
erythroid ratio. Myeloid precursors outnumber erythroid precursors by about 3 or 4 to 1 in the normal bone marrow.
Although there are many more red blood cells in the peripheral blood than granulocytes, red blood cells have a much
longer life span in circulation (120 days) as compared to granulocytes (about 8 hours). Granulocytes, therefore, require a
more continual production than erythrocytes and are the most numerous marrow precursors. Alterations in the M:E ratio,
such as 1:1 or 8:1, may indicate erythroid hyperplasia or granulocytic hyperplasia, respectively.
What is the normal ratio of myeloid to erythroid precursors in bone marrow (M:E ratio)?

A. 1:1
B. 1:3
C. 4:1
D. 8:1
B. Action of majority is lineage restricted

B. A diverse group of growth factors (cytokines) regulate and maintain hematopoiesis in a steady state. Most
hematopoietic growth factors are not lineage restricted but can act on more than one cell type and have multiple functions.
For example, interleukins (IL-3) and colony stimulating factors (GM-CSF) affect multiple cell lines; whereas erythropoietin
action is limited to erythroid cells. Cytokines are glycoproteins that usually express activity by binding to specific receptors
on target cells. The action of growth factors on hematopoietic progenitor and precursor cells can stimulate or inhibit cell
proliferation and differentiation as well as promote or suppress cell death. Growth factors may act alone or together to
exert a positive or negative influence on hematopoiesis as well as on the function of mature cells. A determining factor for
controlling the rate of cell production is cytokine stimulation in response to physiologic
need.
Which of the following does not accurately describe hematopoietic growth factors?

A. Bind to target cell receptors to express

activity
B. Action of majority is lineage restricted
C. May promote or suppress cell death
D. Can stimulate or inhibit cell
proliferation
A.Liver

A. The liver of the fetus assumes responsibility for hematopoiesis about the second month of gestation. From 3 to 6
months of fetal development, the spleen, thymus, and lymph nodes are also involved, but the principal site of
hematopoiesis remains the liver. By the seventh gestational month, the bone marrow becomes the primary hematopoietic
site. Around birth, the liver and spleen have ceased hematopoiesis (except for splenic lymphopoiesis) but maintain the
potential for reactivation of hematopoiesis.
In the third month of gestation, what is the primary site of hematopoiesis?

A.Liver
B. Marrow of long bones
C. Spleen
D. Yolk sac
B. Kidney

B. Erythropoietin (EPO) is a hormone that stimulates red cell production in the bone marrow by its action on the
committed RBC progenitor cells. To maintain optimal erythrocyte mass for tissue oxygenation, the body's mechanism for
sensing tissue oxygen levels is located in the kidney. Erythropoietin production increases when hypoxia is detected by
renal oxygen sensors, with 90% being synthesized in the kidney and 10% in the liver. EPO levels in the blood vary
according to the oxygen carrying capacity of the blood (e.g., EPO levels rise in anemia and fall when tissue oxygen levels
return to normal).
The mechanism that relays information about tissue oxygen levels to erythropoietin-producing sites is located in the

A. Brain
B. Kidney
C. Liver
D. Spleen
D. Thymus and bone marrow

D. The marrow-derived common lymphoid progenitor cell ultimately gives rise to lymphocytes of T, B, or NK (presumably)
cell lineages. Antigenindependent lymphopoiesis occurs in primary lymphoid tissue located in the thymus and bone
marrow. The formation of immunocompetent T and B cells from precursor cells is influenced by environment (thymus,
bone marrow) and several interleukins. Antigen dependent lymphopoiesis occurs in secondary lymphoid tissue (spleen,
lymph nodes, Peyer's patches of the gastrointestinal tract) and begins with antigenic stimulation of immunocompetent
cells
Antigen-independent lymphopoiesis occurs in primary lymphoid tissue located in the

A. Liver and kidney

B. Spleen and lymph nodes
C. Peyer's patches and spleen
D. Thymus and bone marrow
B. Apoptosis

B. Apoptosis is physiological cell death that can be induced by deprivation of growth factors or prevented by growth-
promoting cytokines. Apoptosis plays an important role in the regulation of cell number and is deregulated in certain
malignancies. Necrosis is accidental cell death by phagocytic cells and is associated with lethal physical damage. Cellular
senescence describes cells that have lived their life span and will die of old age. Terminal differentiation refers to mature
end-stage cells that are no longer capable of replication
Programmed cell death is called

A. Necrosis
B. Apoptosis
C. Cellular senescence
D. Terminal differentiation
A. Cords

A. Bone marrow consists of vessels, nerves, hematopoietic cells at various levels of maturation, and stromal cells
encased in a membrane lining called the endosteum. The vascular system empties into a system of sinuses (venous
sinusoids). A layer of endothelium lines these sinusoids. Blood cell formation occurs in hematopoietic cords located
outside of the sinusoids and between the trabeculae of spongy bone. The bone marrow stroma (macrophages,
adipocytes, fibroblasts, endothelial cells) forms an optimal microenvironment for developing cells by providing support and
secreting cytokines. Mature differentiated cells can deform to penetrate the vessel wall and enter the sinuses and blood
circulation.
In what area of the bone marrow does hematopoiesis take place?

A. Cords
B. Endosteum
C. Endothelium
D. Sinuses
B. Hematopoietic tissue to adipose tissue

B. Bone marrow cellularity in the normal adult is approximately 50% hematopoietic tissue and 50% adipose tissue (fat),
with a range of 30- 70% cellularity being normocellular. Marrow cellularity is usually estimated from the core biopsy. An
intact bone marrow can respond to demand by increasing its activity several times the normal rate if sufficient supplies
and growth factors are available. The marrow becomes hypercellular when inactive fatty tissue is replaced by active
hematopoietic marrow. In contrast, bone marrow failure may result in hypocellularity or aplasia with increased fat and a
reduced number of hematopoietic cells.
Bone marrow cellularity refers to the ratio of

A. Red cell precursors to white cell precursors

B. Hematopoietic tissue to adipose tissue
C. Granulocytic cells to erythrocytic cells
D. Extravascular tissue to intravascular tissue
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C. Monocytes and T lymphocytes

C. Interleukins and colony stimulating factors are cytokines produced by a variety of cells, including
monocytes/macrophages, T lymphocytes, fibroblasts, and endothelial cells. It is essential that cytokines are continuously
supplied by cells present in the bone marrow microenvironment during hematopoietic cell development, or cells will die.
Erythropoietin functions as a true hormone because it is produced by the kidney, released into the blood, and carried to
the bone marrow, where it stimulates red cell production.
Interleukins and colony stimulating factors are cytokines produced by

A. B lymphocytes and erythrocytes

B. Erythrocytes and thrombocytes
C. Monocytes and T lymphocytes
D. Neutrophils and monocytes
C. 6L

C. In a normal adult, the total blood volume is approximately 12 pints or 6 liters. Cells account for about 45% (44% is red
cell mass) and plasma accounts for 55%. Alterations in red cell mass or plasma volume are reflected in the RBC count
and in measurements of hemoglobin and hematocrit.
True anemia or polycythemia is due to a decrease or increase in total RBC mass, respectively. A reduction in plasma
volume with a normal RBC mass may cause relative (pseudo) polycythemia. Conversely, an increase in plasma volume
with normal RBC mass may cause relative (pseudo) anemia.
What is the approximate total blood volume in an adult?

A. 1L
B. 2L
C. 6L
D. 12L
A. Granulocytic, erythrocytic, monocytic, or megakaryocytic lineages

A. The pluripotent hematopoietic stem cell gives rise to lymphoid and myeloid progenitor cells. The lymphoid progenitor
produces cells destined to become lymphocytic cells, whereas the myeloid progenitor cell produces progenitors
committed to differentiation into granulocytic, erythrocytic, monocytic, or megakaryocytic lineages with appropriate
stimulus. The cells produced by progenitor cells can be demonstrated using in vitro culture techniques; thus, the myeloid
progenitor cell is termed CPU (colony forming unit)-GEMM based on the cell colonies formed.
The myeloid progenitor cell can produce cells committed to

A. Granulocytic, erythrocytic, monocytic, or megakaryocytic lineages

B. Granulocytic, monocytic, lymphocytic, or megakaryocytic lineages
C. Erythrocytic, granulocytic, monocytic, or lymphocytic lineages
D. Erythrocytic, granulocytic, lymphocytic, or megakaryocytic lineages
C. Megakaryocytes

C. The mature megakaryocyte, the largest hematopoietic cell in normal bone marrow, has a multilobed nucleus and
abundant, granular cytoplasm. Plasma cells are characterized by a round, eccentric nucleus and intensely blue
cytoplasm. Osteoblasts and osteoclasts are nonhematopoietic cells that may be present in normal bone marrow.
Osteoblasts are cells involved in bone formation that resemble plasma cells but are larger and often found in groups.
Osteoclasts reabsorb bone and are similar to megakaryocytes in size but are multinucleated.
The largest hematopoietic cells in normal bone marrow are

A. Osteoblasts
B. Osteoclasts
C. Megakaryocytes
D. Plasma cells
D. The presence of 10% myeloblasts on the cell differential count

D. In normal adult marrow, about 50% is fat, 40% is myeloid (granulocytic) cells, and 10% is erythroid cells. The M:E ratio
is determined by performing a differential count of marrow precursor cells. The presence of 10% myeloblasts is an
abnormal finding (reference range 0-2%), and a hematologic disease is likely. Megakaryocytes should be seen when
scanning and are usually reported as normal, increased, or decreased in number. Marrow iron is assessed with Perl's
Prussian blue stain, and it is normal to see stainable iron in macrophages, as well as iron granules in the cytoplasm of
developing red cell precursors
When evaluating a bone marrow aspirate smear, which finding is considered abnormal?

A. A predominance of granulocyte precursors as compared to nucleated red cells

B. Detection of stainable iron in
macrophages and erythroid precursors with Prussian blue
C. An average of three megakaryocytes seen per low power (10X) field
D. The presence of 10% myeloblasts on the cell differential count
B. Nucleus to cytoplasm ratio (N:C) decreases

B. The nucleus-to-cytoplasm ratio decreases as blood cell lines mature. With maturation, cells generally become smaller,
the nuclear chromatin becomes clumpy and condensed, nucleoli disappear, and the cytoplasm loses its deep blue
basophilia when stained with Wright's stain. Exceptions include megakaryocytes (because of endomitosis they grow larger
as cytoplasm accumulates) and plasma cells (increased RNA and protein synthesis produces a deep basophilia).
As most blood cell lines mature, which of the following is characteristic?

A. Cell diameter increases

B. Nucleus to cytoplasm ratio (N:C) decreases
C. Nuclear chromatin becomes less condensed
D. Basophilia of the cytoplasm increases
C. Hormone produced by the liver that stimulates megakaryopoiesis

C. Thrombopoietin (TPO) is the major regulator of platelet production in the bone marrow by its action on committed
progenitor and precursor cells of the megakaryocytic line. It is primarily produced by hepatocytes and possibly by the
kidney. After marrow release, about 70% of platelets are in the blood circulation and 30% are sequestered in the spleen.
Unlike erythropoietin, which is manufactured for routine therapeutic use, recombinant TPO is still being evaluated.
Which of the following describes thrombopoietin (TPO)?

A. Renal hormone that regulates marrow red cell production

B. Marrow hormone secreted by developing megakaryoblasts
C. Hormone produced by the liver that stimulates megakaryopoiesis
D. Pituitary hormone that controls platelet sequestration by the spleen
B. Myeloid metaplasia or extramedullary

B. Hematopoiesis within the medulla or inner part of the bone marrow is termed medullary or myeloid. Hematopoiesis that
occurs in the liver and spleen (reactivation of fetal life) is called extramedullary or myeloid metaplasia (organs may
enlarge). Cell production outside of the marrow space takes place when the bone marrow is unable to meet its production
demands. This may occur in severe hemolytic anemias when the maximal capacity of the bone marrow to increase
activity is exceeded. Myeloid metaplasia may also be an extension of a disease process such as myelofibrosis.
Myelophthisis refers to the replacement of normal marrow hematopoietic tissue by fibrotic tissue or cancer cells, whereas
myelodysplasia describes abnormal maturation of erythrocytic, granulocytic, and/or megakaryocytic cell lines. The period
of intrauterine life when cell production occurs in the yolk sac may be termed mesoblastic.
When the hepatic phase of fetal life is reactivated in an adult, hematopoiesis can be termed

A. Myeloid or medullary
B. Myeloid metaplasia or extramedullary
C. Myelophthisis or myelodysplasia
D. Mesoblastic or mesenchymal

D. 120 days

D. Normal red blood cells survive about 4 months, or 120 days. The entire life span of the red cell is spent inside the
vascular tree, making it easier to determine the rate of production and destruction. Red cell survival depends upon an
intact RBC membrane, sufficient cellular energy, and normal hemoglobin function. As red cells circulate for 120 days,
enzymes are depleted and the ability to deform decreases. Under normal conditions, red cell loss due to aging (-1%) is
equal to daily replacement. Most destruction of aged red cells occurs extravascularly by macrophages of the
reticuloendothelial system (spleen, liver).
What is the average life span of a normal red blood cell?

A. 1 day
B. 10 days
C. 60 days
D. 120 days
B. Intracellular K+

B. The erythrocyte has a semipermeable membrane that allows water and some anions, such as chloride (CF) and
bicarbonate HCOs , to enter the cell rapidly. Sodium ions (Na+) enter the cell and potassium ions (K+) leave the cell
slowly but continuously. In order to maintain a high intracellular K+ concentration and remove excess Na+, ATP-
dependent cationic pumps expel Na+ and take in K+. This regulation of intracellular cations allows the red cell to control
its volume and water content.
The Na+-K+ cation pump is an important mechanism in keeping the red blood cell intact. Its function is to maintain a high
level of
A. Intracellular Na+
B. Intracellular K+
C. Plasma Na+
D. Plasma K+
D. Four heme groups, four globin chains

D. A molecule of hemoglobin is composed of four globular, protein subunits, and each subunit contains a heme group
bound within a convoluted globin chain. Heme groups are identical and consist of protoporphyrin IX with a central iron
atom, made largely in the mitochondria. Amino acids are sequenced on ribosomes to produce four types of globin chains
(alpha, beta, delta, and gamma) that combine in identical pairs. A normal hemoglobin molecule consists of two alpha-
globin chains and two non-alphaglobin chains, each of which binds a heme group. The different globin chains determine
the hemoglobin type (A, A2, or F).
Which of the following depicts the structure of the hemoglobin molecule?

A. Two heme groups, two globin chains

B. Four heme groups, two globin chains
C. Two heme groups, four globin chains
D. Four heme groups, four globin chains
D. Removal of abnormal red cells by the spleen

D. Culling is the process of removing aged or abnormal red blood cells from the circulation by the spleen. Red cells (7 um)
enter the spleen through the splenic artery and must squeeze back into active circulation through 2- to 4-um clefts in the
venous sinusoids. Aged or abnormally shaped red cells with impaired membrane flexibility are trapped in the splenic
microcirculation and ingested by macrophages. The spleen is the largest filter of blood in the body and has an essential
role in the "quality control" of red cells
Which of the following describes the process known as culling?

A. Release of red cells from the bone marrow

B. Binding of free hemoglobin by transport proteins
C. Incorporation of iron into protoporphyrin IX
D. Removal of abnormal red cells by the spleen
C. Carboxyhemoglobin and methemoglobin

C. Each hemoglobin molecule has four heme groups located at its surface, and oxygen binds to the central ferrous iron
(Fe2+) in heme. Deoxyhemoglobin (not carrying O2) and oxyhemoglobin (carrying up to four O2) are normal physiologic
forms of hemoglobin with iron in the ferrous state. Hemoglobin in which the ferrous iron (Fe 2+ ) has been oxidized to the
ferric state (Fe 3+ ) is known as methemoglobin and is unable to carry O2. Carboxyhemoglobin is hemoglobin with carbon
monoxide (CO) attached to ferrous iron rather than O2. Both methemoglobin and Carboxyhemoglobin are reversible.
Hemoglobin forms that are incapable of oxygen transport include

A. Deoxyhemoglobin and oxyhemoglobin

B. Oxyhemoglobin and carboxyhemoglobin
C. Carboxyhemoglobin and methemoglobin
D. Methemoglobin and deoxyhemoglobin
C. Hemoglobin

C. Of the total body iron present in a normal adult, approximately 70% is contained in hemoglobin (in red cells of the blood
and marrow). Most of the remainder, -25%, is found in storage sites as ferritin or hemosiderin. A much smaller amount of
iron is contained in muscle myoglobin (4%) and respiratory enzymes such as peroxidase (1%). The structures of
hemoglobin and myoglobin are similar (both consist of globin and heme), but myoglobin functions as an oxygen trap in the
tissues.
The majority of iron found in an adult is a constituent of

A. Ferritin
B. Myoglobin
C. Hemoglobin
D. Peroxidase
B. Lived its life span

B. A senescent red blood cell is one that has lived its life span. Repeated passes through the spleen deplete the cells of
glucose and decrease their surface area as membrane lipids are lost. The red cells are removed from the circulation by
splenic macrophages that recognize subtle abnormalities in these cells, sequester them, and destroy them
A senescent red blood cell is one that has

A. Been hemolyzed
B. Lived its life span
C. Become deformed
D. Lost its mitochondria
B. Deviations from normal shape

B. "Poikilocytosis" is a general term that refers to deviations from the normal red cell shape (biconcave, discoid).
"Anisocytosis" is the term used when differences in the sizes of red cells are described. Color in red cells is designated as
normochromic (normal) or hypochromic (indicating a decreased hemoglobin concentration). Abnormally shaped red cells
and red cell inclusions are associated with rigid red cells that have reduced deformability and shortened survival.
What red cell morphologic abnormality is described by the term "poikilocytosis"?

A. Variations in size
B. Deviations from normal shape
C. Presence of inclusions
D. Alterations in hemoglobin concentration
A. DNA

A. Howell-Jolly bodies are nuclear (DNA) remnants that remain in the red cell after the nucleus has been extruded and
may represent nuclear instability. These inclusions are associated with the defective nuclear maturation found in
megaloblastic anemias and the rapid cell division that occurs in severe hemolytic anemias. Under normal circumstances,
the spleen effectively pits these bodies from the cell. Pitting is a process that removes inclusions while leaving the rest of
the red cell intact. It may be that the pitting mechanism is overwhelmed and cannot keep pace with inclusion formation in
hemolytic anemias. Howell-Jolly bodies can also be seen in individuals after splenectomy who lack the normal pitting
function.
Howell-Jolly bodies are composed of

A. DNA
B. Iron
C. Reticulura
D. RNA
A. Red cells without a central pallor

A. Spherocytes appear smaller and more densely staining than normal red cells and lack a central pallor area. Because
they are the result of membrane loss, their surface area-to-volume ratio is decreased. Spherocytes should be
distinguished from acanthocytes, which also lack a pallor area but have sharp, irregular projections. Echinocytes have a
central pallor area and blunt, short projections. Red cells with intracellular rod- or bar-shaped crystals contain hemoglobin
C crystals
When spherocytes are reported, what is observed on the peripheral blood smear?

A. Red cells without a central pallor

B. Red cells with blunt projections
C. Red cells with sharp projections
D. Red cells with intracellular rod-shaped crystals
B. Aggregated ribosomes; basophilic stippling

B. The presence of lead causes an inhibition of several of the enzymes important in heme synthesis. Among these is
pyrimidine 5' nucleotidase, which is normally responsible for degradation of ribosomal ribonucleic acid (RNA). The lack of
this enzyme apparently allows aggregates of incompletely degraded RNA to remain in the cell cytoplasm. It is this
ribosomal material that appears on Wright's stain as punctate basophilic stippling. Precipitated hemoglobin forms Heinz
bodies (not visible with Wright's stain), nuclear fragments are called Howell-Jolly bodies, and iron deposits are
Pappenheimer bodies.
The red cells found in lead poisoning characteristically exhibit coarse granules composed of that are reported as

A. Precipitated hemoglobin; Pappenheimer bodies

B. Aggregated ribosomes; basophilic stippling
C. Nuclear fragments; Pappenheimer bodies
D. Excess iron deposits; basophilic stippling
D. Multiple myeloma
D. The presence of red cell rouleaux (coining pattern) is a characteristic finding in multiple myeloma because of the
increased concentration of immunoglobulins in the blood plasma (hypergammaglobulinemia). The excessive
immunoglobulins
are produced by malignant plasma cells. Cold hemagglutinin disease is characterized by red cell agglutination or clumping
in a nonspecific pattern. "Hypersplenism" refers to an enlarged, overactive spleen that destroys both normal and abnormal
cells, possibly causing pancytopenia
Rouleaux of red blood cells when seen in the monolayer of a blood smear is characteristic of

A. Hypersplenism
B. Hypogammaglobulinemia
C. Cold hemagglutinin disease
D. Multiple myeloma
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C. Post-splenectomy

C. In viewing Color Plate 1, the inclusions in the red blood cells are Howell-Jolly bodies. During passage through the
microvessels of the spleen, the red cell is examined for intracellular inclusions or membrane-bound antibodies, which, if
present, are removed. Abnormal red cells circulate longer, and inclusions such as Howell-Jolly bodies or Pappenheimer
bodies will be seen postsplenectomy (or in conditions with splenic atrophy). The phagocytic removal of abnormal red cells
is assumed by the liver, but the liver is not as efficient as the spleen. Howell-Jolly bodies are not associated with iron
deficient or iron overload states.
Which of the following is most frequently associated with the inclusion bodies seen in Color Plate 1?

A. Iron overload state

B. Post-transfusion
C. Post-splenectomy
D. Iron-deficient state
C. Absorption increases when erythropoietic activity increases.

C. One of the reasons for increased intestinal absorption of iron is an accelerated rate of erythropoiesis (another is
depletion of iron stores). Although the mucosal cell does act as a barrier in normal circumstances, this function is not
absolute and controls break down in the presence of large amounts of iron, causing an excess to be absorbed. An acid
pH is required for iron absoiption, and sites of maximal absorption are the duodenum and upper jejunum. The body has
no effective means for iron excretion.
Which of the following statements about iron absorption is true?

A. Absorption occurs in the ileum.

B. The mucosal cell always absorbs the correct amount of iron to meet needs.
C. Absorption increases when erythropoietic activity increases.
D. Alkaline pH favors absoiption.
D. Siderocyte

D. The presence of iron granules or deposits can be detected with Perl's Prussian blue iron stain. Siderocytes are mature
red blood cells that contain stainable iron granules (abnormal). Sideroblasts are bone marrow nucleated red cells
(normoblasts) that contain small amounts of iron in the cytoplasm (normal). Ringed sideroblasts are marrow normoblasts
that contain iron in the mitochondria that forms a ring around the nucleus (abnormal). Siderocytes and ringed sideroblasts
are associated with iron overload problems, particularly sideroblastic anemia. Reticulocytes may contain small amounts of
unused iron that is normally
removed by the spleen.
What term describes a mature red blood cell that contains iron granules or deposits?

A. Siderosome
B. Sideroblast
C. Ringed sideroblast
D. Siderocyte
C. Decreased oxygen release

C. A "shift to the left" in the oxygen dissociation curve of hemoglobin means that a higher percentage of hemoglobin will
retain more of its oxygen at a given pressure. Thus affinity will be greater and oxygen delivery will be reduced. A higher or
more alkaline pH and a lower temperature are associated with decreased oxygen dissociation. With conditions in the
lungs (increased pH, decreased 2,3-BPG, decreased temperature), hemoglobin affinity for oxygen is increased, which
favors oxygen uptake. With conditions in the tissues (decreased pH, increased 2,3-BPG, increased temperature),
hemoglobin affinity for oxygen is decreased, which favors release of oxygen to the tissues.
Which of the following is associated with a "shift to the left" in the oxygen dissociation curve of hemoglobin?

A. Decreased pH and elevated temperature

B. Decreased oxygen affinity
C. Decreased oxygen release
D. Presence of 2,3-bisphosphoglycerate
(2,3-BPG)
D. Decreases stimulation of erythropoiesis when cellular hypoxia increases

D. Erythropoietin (EPO) is a hormone produced by the kidney that increases erythropoiesis in the bone marrow in
response to tissue hypoxia. The CFU-E (colony-forming unit erythroid) is a committed erythroid progenitor cell with many
receptors for erythropoietin. EPO stimulation of the CFU-E produces the recognizable pronormoblast and promotes
differentiation of RBC precursors. The maturation time of erythrocyte precursors (5-7 days) can be reduced in times of
increased need for red cells by the action of erythropoietin.
Which of the following statements does not characterize erythropoietin (EPO)?

A. Transforms the CFU-E into the earliest recognizable RBC precursor

B. Increases the rate of red blood cell production by the bone marrow
C. Shortens the maturation time of developing erythroid precursors
D. Decreases stimulation of erythropoiesis when cellular hypoxia increases
C. Increased hemoglobin binding of 2,3-BPG

C. Increased binding of 2,3-BPG (2,3-bisphosphoglycerate) decreases the affinity of hemoglobin for oxygen, which
promotes oxygen release to the tissues, a compensatory mechanism in anemic patients. Increased pH (alkalinity)
enhances oxygen affinity and thus inhibits delivery to the tissues. Less oxygen is available at higher altitudes, and this
affects blood saturation and delivery to tissues. An increase in erythropoietin release will affect red cell production but
does not have an immediate or direct impact on oxygen delivery.
Which of the following factors will result in an immediate increase in oxygen delivery to the tissues?

A. Increased pH
B. High altitudes
C. Increased hemoglobin binding of 2,3-BPG
D. Increased renal release of erythropoietin
A. Loss of residual RNA occurs immediately upon marrow release

A. After the nucleus is extruded, reticulocytes spend about 2 days in the bone marrow before release into the blood,
where maturation continues for another day. Intense erythropoietin stimulus can cause early release of bone marrow
reticulocytes. These reticulocytes are larger and contain more filamentous reticulum than a more mature reticulocyte.
These "shift" or "stress" reticulocytes exhibit diffuse basophilia on the Wright's stained smear and will need more than the
usual 1 day in circulation to mature (to lose RNA). A very high number of reticulocytes in the blood circulation can
increase the MCV. The level of reticulocyte maturity is best assessed by the immature reticulocyte fraction (IRF), an index
reported by automated cell counters that is based on RNA content
Periods of intense erythropoietin activity cause premature release of marrow reticulocytes into the blood. Which of the
following is not true of these early reticulocytes?

A. Loss of residual RNA occurs immediately upon marrow release

B. Circulate longer than usual before reaching maturity
C. May be termed shift or stress reticulocytes
D. Show diffuse basophilia with Wright's stain
C. Heinz bodies

C. Heinz bodies do not stain with Wright's stain and appear as "normal" hemoglobin even though their presence causes
cell rigidity and membrane damage. They can be visualized on wet preps with phase microscopy or by using supravital
stains, such as crystal violet or brilliant green. Heinz bodies consist of intracellular globin or hemoglobin precipitate that
results from hemoglobin denaturation (G6PD deficiency, unstable hemoglobin valiants) or excess globin chains (certain
thalassemic syndromes). Basophilic stippling, Cabot rings, and Pappenheimer bodies are visible with both Wright's and
supravital stains.
Which of the following inclusions is only visible with supravital staining?

A. Basophilic stippling
B. Cabot rings
C. Heinz bodies
D. Pappenheimer bodies

B. Increased red cell destruction

B. The presence of schistocytes (schizocytes) on the smear indicates that red cells have been subjected to some form of
physical trauma that causes damage. Red cell fragmentation can be the result of impact with fibrin strands, mechanical
trauma by artifical surfaces, injury by heat, partial phagocytosis, or damage by toxins and drugs. Schistocytes are
characteristic of the increased red blood cell destruction that occurs in severe hemolytic anemias but are not associated
with
The presence of schistocytes on the peripheral blood smear is commonly associated with

A. Increased iron mobilization

B. Increased red cell destruction
C. Decreased erythropoietin activity
D. Decreased red cell proliferation
C. Nucleated red cells in the peripheral circulation

C. Tissue hypoxia associated with low erythrocyte and hemoglobin levels causes increased renal release of erythropoietin
to stimulate bone marrow erythropoiesis. Depending on severity, the bone marrow responds by increasing its activity 6-8
times normal and becomes hypercellular because of an increase in RBC precursors (erythroid hyperplasia); and the M:E
ratio falls. Nucleated red cells may be released into the blood along with the outpouring of reticulocytes. The number of
nucleated red cells tends to correlate with anemia severity.
Which of the following may be a sign of accelerated bone marrow erythropoiesis?

A. Hypercellular marrow with a decreased number of RBC precursors

B. Bone marrow M:E ratio of 6:1
C. Nucleated red cells in the peripheral circulation
D. Low erythrocyte, hemoglobin, and hematocrit levels
C. Hemoglobin synthesis

C. Millions of hemoglobin molecules are produced in the red cell cytoplasm during maturation. When developing erythroid
cells are deprived of essential hemoglobin components, the result is the production of microcytic, hypochromic red cells. It
is thought that during maturation, extra cell divisions occur until a certain hemoglobin concentration is reached. Impaired
hemoglobin synthesis may be the result of heme defects (involving iron or protoporphyrin) or may be caused by globin
defects. Impaired DNA synthesis is associated with macrocytic red cells, and normocytic red cells are characteristic of
enzyme defects.
Microcytic, hypochromic red cells are most often associated with impaired

A. DNA synthesis
B. RNA metabolism
C. Hemoglobin synthesis
D. Enzyme metabolism
C. Orthochromic normoblasts

C. The nucleated red cells seen in Color Plate 2 would be staged as orthochromic normoblasts (metarubricytes) when in
the bone marrow. This is the last stage of red cell maturation that contains a nucleus. The pyknotic, degenerated nucleus
is normally extruded out of the red cell in the marrow to yield the anucleate reticulocyte. The release of nucleated red cells
into the blood before reaching maturity usually indicates a high demand for red cells.
When in bone marrow, the nucleated red cells present in Color Plate 2 would be staged as

A. Basophilic normoblasts
B. Polychromatophilic normoblasts
C. Orthochromic normoblasts
D. Pronormoblast
B. Altered membrane lipids

B. The red cell membrane consists of a protein shell heavily coated with lipids. The membrane lipid bilayer is maintained
by constant interchange with plasma lipids. Acanthocytes are the result of abnormal plasma lipids that have altered the
lipid composition of the membrane, often involving increased cholesterol content. Acanthocytes (spur cells) are associated
with a congenital form of acanthocytosis and with liver disease, or are seen following splenectomy.
When acanthocytes are found on the blood smear, it is usually the result of

A. Abnormal membrane permeability

B. Altered membrane lipids
C. Mechanical trauma
D. Polymerization of hemoglobin molecules
A. Embden-Meyerhof

A. The mature red cell, which lacks mitochondria and Kreb's cycle activity, depends on glucose metabolism for cellular
energy. The end product of the anaerobic Embden-Meyerhof pathway (BMP) is ATP, which is necessary for membrane
maintenance and volume control (cation pumps). The hexose monophosphate (HMP) pathway is aerobic and reduces
oxidants by providing NADPH and glutathione. The Rapoport-Luebering shunt controls the amount of 2,3-
bisphosphoglycerate that regulates hemoglobin affinity for oxygen. Oxidized hemoglobin (methemoglobin) is reduced to
functional hemoglobin by the methemoglobin reductase pathway
Which erythrocyte metabolic pathway generates adenosine triphosphate (ATP) via glycolysis?

A. Embden-Meyerhof
B. Hexose monophosphate
C. Rapoport-Luebering
D. Methemoglobin reductase
C. Polychromatophilic normoblast

C. The polychromatophilic normoblast (rubricyte) is the last red cell stage capable of mitosis. With cellular divisions, each
pronormoblast produces up to 16 erythrocytes. The polychromatophilic normoblast is also the stage in which hemoglobin
is first visible. The gray-blue color of the cytoplasm when Wright's stained is due to a mixture of hemoglobin and RNA,
hence the name "polychromatophilic." The reticulocyte is the last stage able to synthesize hemoglobin.
Which of the following red blood cell precursors is the last stage to undergo mitosis?

A. Pronormoblast
B. Basophilic normoblast
C. Polychromatophilic normoblast
D. Orthochromic normoblast
A. Beta-globin chains

A. The major adult hemoglobin, Hb A, consists of two alpha- and two beta-globin chains. The switch from gamma chains
(Hb F) to beta chains occurs 3-6 months after birth, and Hb A reaches adult levels (about 97%) around 6 months of age.
Most globin chains produced in a normal adult are alpha and beta types (1:1 ratio) for hemoglobin A production.
Hemoglobin A2 contains delta chains and comprises about 2% of hemoglobin in normal adults. Epsilon chains are found
in early embryonic hemoglobins only
The major adult hemoglobin requires the synthesis of alpha-globin chains and

A. Beta-globin chains
B. Delta-globin chains
C. Epsilon-globin chains
D. Gamma-globin chains
C. Macrocytic

C. Impaired DNA synthesis results in nuclear maturation that lags behind cytoplasmic development (asynchrony),
decreased cellular divisions, and the production of macrocytic red cells. Defective nuclear maturation (megaloblastic) is
almost always caused by a deficiency of vitamin B12 or folic acid, which are DNA coenzymes. Macrocytic red cells that
are not due to vitamin B12 or folic acid deficiency (nonmegaloblastic) may be seen in liver disease or when reticulocytosis
is pronounced. Microcytic, hypochromic red cells are the result of impaired hemoglobin synthesis.
Defective nuclear maturation commonly results in the production of red cells that are

A. Normocytic
B. Hypochromic
C. Macrocytic
D. Microcytic
A. Ferritin
A. When iron is removed from the heme of destroyed red blood cells, it is bound to transferrin and recycled for
hemoglobin production or goes to storage. The major storage form of iron is ferritin, which is a water-soluble iron complex
bound in a protein shell called apoferritin. Hemosiderin is a water-insoluble complex of iron aggregates and protein that is
derived from ferritin. The main site of iron stores is the liver, but storage iron is also found in the bone marrow and spleen.
The major storage form of iron is

A. Ferritin
B. Transferrin
C. Hemosiderin
D. Hemachromatin
B. MCV 90.0 fL, RDW 25.0%

B. RBC indices are average values, so they have less meaning in heterogeneous RBC populations with wide size
variations. Because the MCV is a mean red cell volume measurement, the presence of both microcytes and macrocytes
would yield a falsely normal MCV value. One would expect the RDW (red blood cell distribution width) to be high because
it is an index of variation in red cell size or anisocytosis. The RDW is low when red cells are of uniform size (a
homogeneous population). The RDW is high when a heterogeneous population of red cells is present.
The red cells observed on a peripheral blood smear show extreme anisocytosis with an equal number of macrocytes and
microcytes. Which of the following values correlate with this finding?

A. MCV 108.0 fL, RDW 14.0%

B. MCV 90.0 fL, RDW 25.0%
C. MCV 75.0 fL, RDW 16.0%
D. MCV 88.0 fL, RDW 12.0%
B. Bilirubinemia

B. Bilirubin is formed when hemoglobin degradation occurs in the reticuloendothelial system, primarily in the spleen.
Unconjugated bilirubin is transported by the plasma to the liver, where it is conjugated. When excessive extravascular red
cell destruction occurs, the plasma bilirubin level rises and is largely unconjugated bilirubin. When acute intravascular red
cell destruction occurs, hemoglobin is released into the plasma and findings may include hemoglobinemia,
hemoglobinuria, and hemosiderinuria.
Excessive extravascular red cell destruction is associated with

A. Hemoglobinemia
B. Bilirubinemia
C. Hemoglobinuria
D. Hemosiderinuria
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D. Haptoglobin

D. Haptoglobin forms a 1:1 complex with alpha-beta dimers of hemoglobin. The large size of this complex prevents
filtration of the hemoglobin through the kidneys, where it can cause renal damage. Haptoglobin can be depleted in the
plasma during major hemolytic events, such as malarial attacks, transfusion reactions, and other causes of severe
intravascular red cell destruction.
Which protein is primarily responsible for transport of hemoglobin dimers resulting from intravascular hemolysis?

A. Hemopexin
B. Albumin
C. Hemosiderin
D. Haptoglobin
C. Codocytes

C. Codocytes (target cells) have an increased surface area-to-volume ratio and are associated with abnormal hemoglobin
synthesis. They are found in hemoglobinopathies, especially hemoglobin S or C disorders, as well as thalassemias and
iron deficiency. Target cells can also result from an increase in membrane lipids and may be seen in liver disease.
Discocytes are normal biconcave red cells, and elliptocytes (ovalocytes) can be found in varying sizes. The teardrop
shape of daciyocytes may occur when a red cell is stretched in the spleen and cannot regain its original shape.
The morphologic abnormality characteristically found in hemoglobinopathies is

A. Elliptocytes
B. Dacryocytes
C. Codocytes
D. Discocytes
B. In mitochondria

B. Heme synthesis begins in the mitochondria with the formation of aminolevulinic acid. Formation of the pyrrole ring
structure occurs in the cytoplasm, resulting in the synthesis of coproporphyrinogen III. The final stages of porphyrin
synthesis occur again in the mitochondria, culminating in the formation of heme when ferrous iron is incorporated into
protoporphyrin IX in the presence of ferrochelatase.
Where do the early and late stages of heme synthesis occur?

A. On ribosomes
B. In mitochondria
C. In cytoplasm
D. In nucleoli
A. Red cell membrane structure

A. The red cell membrane consists of an outer bilayer of lipids with embedded, integral proteins and an underlying
skeleton. Spectrin is the predominant skeletal protein that forms a cytoskeleton with other proteins, such as actin, protein
4.1, and ankyrin. The skeletal proteins are responsible for cell shape, deformability, and stability. Any defect in structure or
extensive damage to the membrane cannot be repaired and may lead to premature red cell death.
Spectrin is a protein that occupies a major role in

A. Red cell membrane structure

B. Reducing ferric iron
C. Red cell transport and removal of CC>2
D. Iron recovery during hemoglobin degradation
C. Neutralizes intracellular oxidants that accumulate

C. Reduced glutathione (GSH) counteracts oxidants that accumulate in the red cell. These occur as a result of normal
metabolic activities and increase during infections or as a result of treatment by certain drugs. In the absence of GSH or
as a result of enzyme deficiencies in the hexose monophosphate pathway (HMP), oxidant accumulation can lead to
oxidation and precipitation of hemoglobin.
What is the function of reduced glutathione (GSH) in the red blood cell?

A. Promotes Kreb's cycle activity

B. Maintains anion balance during the "chloride shift"
C. Neutralizes intracellular oxidants that accumulate
D. Prevents oxygen uptake by hemoglobin
C. Amount of iron that transferrin can bind

C. Total iron-binding capacity (TIBC) represents the amount of iron that circulating transferrin could bind when fully
saturated. In this test, the amount of transferrin protein in the serum is indirectly measured by adding feme (Fe3+) iron to
the serum and allowing it to bind to the unsaturated sites on transferrin. Unbound iron is then removed and the sample
analyzed for the remaining iron that is bound to transferrin. The serum iron level measures iron bound to transferrin.
Under normal conditions, about one-third of the binding sites on transferrin are occupied with iron
What does measuring the total ironbinding capacity (TIBC) represent?

A. Amount of free iron in serum

B. Circulating protein-bound iron
C. Amount of iron that transferrin can bind
D. Indirect measurement of iron stores
B. Storage iron

B. The amount of circulating ferritin indirectly reflects the amount of storage iron in the tissues. A bone marrow exam is
not essential to assess iron stores, except in complicated cases, because the serum ferritin test is considered a good
indicator of iron storage status in most individuals. Because ferritin is an acute-phase reactant, it may be increased in
chronic inflammatory disorders regardless of iron stores. Therefore, the serum ferritin should be interpreted with other iron
tests. The percent transferrin saturation is the serum iron divided by the serum TIBC.
Serum ferritin is a good indicator of the amount of

A. Cytochrome iron
B. Storage iron
C. Hemoglobin iron
D. Transferrin saturation
B. Resists elution from red cells with acid solutions

B. Fetal hemoglobin can be distinguished from adult hemoglobin in red blood cells by the acid elution technique of
Kleihauer and Betke. Only hemoglobin F remains in red blood cells after exposure to a citric acid-phosphate buffer
solution at pH 3.3. Hb F has a higher oxygen affinity than Hb A (less binding of 2,3-BPG), so it carries oxygen well in
utero. Hemoglobin F production decreases after birth, composing less than 1% of total hemoglobin in normal adults. In
certain conditions (thalassemias, hemoglobinopathies), defective beta-chain production can be compensated for by
increased production of gamma chains and formation of hemoglobin F (two alpha and two gamma chains).
Fetal hemoglobin differs from adult hemoglobin in that hemoglobin F

A. Has a lower oxygen affinity

B. Resists elution from red cells with acid solutions
C. Is no longer synthesized after birth in a normal individual
D. Has four gamma-globin chains

D. Megaloblastic anemia

D. Deficiencies of folic acid (folate) and vitamin B12 result in abnormal DNA synthesis and a resultant delay in nuclear
maturation in comparison to cytoplasmic development. These anemias are categorized as megaloblastic because of the
giant red cell precursors observed in the bone marrow. The other anemias are characterized by defects of heme
(sideroblastic anemia and iron-deficiency anemia) or globin synthesis (hemoglobin C disease).
Impaired DNA metabolism is characteristic of

A. Hemoglobin C disease
B. Iron-deficiency anemia
C. Sideroblastic anemia
D. Megaloblastic anemia
A. G6PD gene is located on the X chromosome.

A. G6PD deficiency has a sex-linked inheritance pattern and is the most common enzyme deficiency in the hexose
monophosphate (HMP) shunt. Individuals are asymptomatic unless exposed to oxidants, which compromise the ability of
the glutathione reduction pathway to prevent the oxidation of hemoglobin. The oxidized hemoglobin precipitates in the
form of Heinz bodies, which cause acute intravascular hemolysis. In the most common G6PD variant, the hemolytic
episode is self-limiting, with old red cells that lack enzyme being destroyed and young red cells with some enzyme activity
unaffected.
Which of the following is associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency?

A. G6PD gene is located on the X chromosome.

B. Ongoing intravascular hemolysis occurs.
C. All circulating red cells, including reticulocytes, lack enzyme activity.
D. Splenectomy can relieve the rate of red cell destruction.
B. Glutamic acid replaces lysine on position 26 of the beta chains

B. Hemoglobin nomenclature indicates a number of things. The symbol a2 or a2A indicates the presence of normal adult,
or A, alpha chains. The designation (3226 Glu~>Lys indicates that lysine residues have replaced glutamic acid on position
26 of the beta chains. All types of E hemoglobin show a similar electrophoretic mobility and migrate closely to
hemoglobins C and A2 on cellulose acetate (alkaline pH). Hemoglobin E occurs with the greatest frequency in Southeast
Asia.
In regard to variant hemoglobin E, alpha 2 Beta 2 26 Glu -> Lys, which of the following statements is false?

A. There are two normal alpha chains.

B. Glutamic acid replaces lysine on position 26 of the beta chains.
C. Hemoglobin E is the second most common hemoglobin variant known.
D. Glutamic acid is normally found at position 26 of the beta chain.
C. An intrinsic hereditary defect of red cells should be suspected.

C. The peripheral blood as seen in Color Plate 3

shows numerous elliptocytes (ovalocytes). If they were artifact due to smear preparation, they would be oriented in the
same direction. Hereditary elliptocytosis (HE) is associated with symptomatic hemolytic anemia in only about 10-15% of
the cases, but the presence of an enlarged spleen is evidence of ongoing extravascular destruction. In patients with
chronic hemolysis, gallstones are a common complication because of excess bilirubin catabolism. In most persons with
HE, anemia does not develop because bone marrow production of red cells compensates for the mild shortening of red
cell life span.
Color Plate 3 shows the peripheral blood of a 16-year-old female with a sporadic history of dizzy spells, fainting, and
jaundice. This patient also had a history of periodic abdominal pain related to gallstones. Upon physical examination, she
exhibited mild splenomegaly. Her hemoglobin was 107 g/L (10.7 g/dL), hematocrit was 0.32 L/L (32%), red cell indices
were normal, and the direct antiglobulin test was negative. Based on history and peripheral blood morphology, which of
the following statements is most
likely true ?

A. Hemoglobin S will be revealed by electrophoresis.

B. Tests to confirm iron deficiency should be ordered.
C. An intrinsic hereditary defect of red cells should be suspected.
D. The anemia is secondary to spleen and gallbladder disorders.
B. Cooley beta-thalassemia major

B. Cooley anemia, or beta-thalassemia major, would be the appropriate diagnosis in this case. In this condition, two beta-
thalassemia genes are inherited that result in virtually no hemoglobin A production because no beta-globin chains are
produced. The primary hemoglobin made is hemoglobin F. The severe microcytic anemia results from the destruction of
red cell precursors in the bone marrow (ineffective erythropoiesis) and rigid red cells in the blood that contain unused
alpha-globin chains. Nucleated red blood cells and target cells, as seen in Color Plate 4B, are common, as well as
basophilic stippling. Infants with alpha-thalassemia major die in utero or shortly after birth. Hemoglobin H disease (three-
gene deletion alpha-thalassemia) results from deficient, alpha-chain synthesis that leads to production of Hb H (four beta
chains), an unstable hemoglobin that forms Heinz bodies and causes chronic hemolysis. No clinical manifestations are
seen in patients with hereditary persistence of fetal hemoglobin (HPFH).
A 9-month-old male was seen in the Emergency Department with a femur fracture that had occurred from a fall down the
stairs. Upon physical examination, the physician noted hepatosplenomegaly, extreme pallor, and a slight arrhythmia.
A complete blood count revealed the following:
WBC 12.2 X 1 09/L (1 2.2 X 1 03/(uL)
RBC 3.05 X 1 01 2/L (3.05 X 1 06/(uL)
Hemoglobin 61 g/L (6.1 g/dL)
Hematocrit 0.20 L/L (20%)
MCV 65.5 fL
MCH 20 pg
MCHC 305 g/L (30.5 g/dL)
RDW 25%

The Wright's stained blood smear showed the findings seen in Color Plate 4.
Hemoglobin electrophoresis was ordered with results as follows:
HgbA 0%
HgbA2 3%
HgbF 97%

Which condition is most likely causing the hematologic abnormalities?

A. Alpha-thalassemia major
B. Cooley beta-thalassemia major
C. Hemoglobin H disease
D. Hereditary persistence of
hemoglobin F
C. Hemoglobin SC disease

C. As seen in Color Plate 5, the presence of numerous target cells and SC crystals on the peripheral blood smear
suggests the presence of hemoglobin SC disease. These bizarre crystals are distinguished by one or more blunt,
fingerlike projections that protrude from the cell membrane. Clinically, hemoglobin SC disease is not usually as severe as
sickle cell disease, and electrophoresis shows equal amounts of Hb S and Hb C. Codocytes, in varying numbers, are
typical of hemoglobin S, C, and E disorders.
A 14-year-old African-American male was seen in the clinic for abdominal pain. A complete blood count revealed the
following:
WBC 7.0 X 1 09/L (7.0 X 1 03/|JLL)
RBC 2.90 X 1 01 2/L (2.90 X 1 06/(JiL)
Hemoglobin 85 g/L (8.5 g/dL)
Hematocrit 0.25 L/L (25%)
MCV 86.2 f L
MCH 29.3 pg
MCHC 340 g/L (34.0 g/dL)
ROW 21%

The peripheral smear showed the red blood cell morphology seen in Color Plate 5. What condition is suggested by these
findings?

A. Hemoglobin E disease
B. Hemoglobin S disease
C. Hemoglobin SC disease
D. Hemoglobin C disease
C. Iron deficiency

C. Pica is a clinical finding seen in some patients with iron deficiency. Pica is unusual cravings for nonfood items that may
include dirt, clay, laundry starch, or, most commonly, ice. Among some cultures, pica is a custom (eating dirt) that may
contribute to iron deficiency. In children, lead poisoning often results from the ingestion of dirt or lead-based paint from
toys and may be related to iron deficiency. Porphyrias are a group of inherited disorders characterized by enzyme
deficiencies and abnormal porphyrin metabolism. The presence of pyridoxine (pyridoxal-5'-phosphate or vitamin Bg) is
important to early porphyrin synthesis.
Pica is most commonly associated with which of the following conditions?

A. Pyridoxine deficiency
B. Lack of erythrocyte folate
C. Iron deficiency
D. Porphyrias
B. Dietary insufficiency

B. Folate deficiency is most commonly a result of poor dietary intake of folate alone or in combination with increased
requirements as during pregnancy. Daily requirements for folate are high, and depletion of folate stores can occur within 4
months as compared to vitamin B12, in which deficiency takes at least 2 years to develop (there are high stores). Thus,
dietary deficiency of vitamin B12 is rare, but folate supplements are commonly required during pregnancy or in hemolytic
anemias with excess cell turnover.
Of the following, the leading cause of folate deficiency is

A. Increased requirements
B. Dietary insufficiency
C. Drug inhibition
D. Malabsorption
C. Hemoglobin S is more soluble in dithionite than is normal hemoglobin.

C. The hemoglobin solubility test can detect the presence of hemoglobin S, which is insoluble in the dithionite reagent,
whereas normal hemoglobin A is soluble. A positive screening test, however, does not distinguish between patients with
hemoglobin AS trait, hemoglobin SC disease, and hemoglobin SS disease, so results must be confirmed by
electrophoresis. Sickle cell trait is clinically asymptomatic with target cells only. Disorders prevalent in the malarial belt
(sickle cell trait, G6PD deficiency, hereditary ovalocytosis, thalassemia minor) are thought to impart resistance to
falciparum malaria. Repeated splenic infarctions by sickle cell masses in hemoglobin SS disease cause autosplenectomy
by adulthood
Which of the following statements about sickle cell syndromes is false?

A. Asplenism may result from repeated sickling crises in the homozygous state.
B. Heterozygous persons may be partly protected from infection by falciparum malaria.
C. Hemoglobin S is more soluble in dithionite than is normal hemoglobin.
D. Trait conditions are generally asymptomatic with no sickle cell formation.
D. Idiopathic thrombocytopenic purpura
(ITP)

D. The schistocytes in Color Plate 6 are found in microangiopathic hemolytic anemia and caused by red cells shearing on
fibrin strands deposited in small vessels. Widespread or localized (e.g., kidney) fibrin deposition in DIG, HUS, and TTP
results in red cell fragmentation. In addition, thrombocytopenia is a usual feature of MAHA. ITP is characterized by severe
thrombocytopenia that results from destruction of platelets by autoantibodies, but it is not associated with red cell damage
or anemia.
The findings seen in Color Plate 6 can be found in patients with microangiopathic hemolytic anemia (MAHA). Which of the
following conditions could not be responsible for this type of red cell destruction?

A. Disseminated intravascular coagulation (DIC)

B. Hemolytic uremic syndrome (HUS)
C. Thrombotic thrombocytopenic purpura (TTP)
D. Idiopathic thrombocytopenic purpura (ITP)
C. Increased total iron-binding capacity

C. Ringed sideroblasts result from the accumulation of iron deposits in the mitochondria surrounding the nucleus of
erythroid precursors. The deposits are secondary to a defect in heme synthesis and a pathological finding in sideroblastic
anemia. Blocks in the protoporphyrin pathway required for heme synthesis may be hereditary (rare) or acquired and result
in iron overload with increased marrow iron. Pappenheimer bodies and basophilic stippling are frequent findings on the
blood smear, and increased serum iron, decreased TIBC, increased percent transferrin saturation, and increased serum
ferritin are usual.
Which of the following blood findings does not correlate with the presence of ringed sideroblasts in the bone marrow?

A. Pappenheimer bodies
B. Basophilic stippling
C. Increased total iron-binding capacity
D. Increased percent transferrin saturation
D. Pernicious anemia

D. Reticulocytosis is indicative of increased erythropoietic activity by the bone marrow. This is a normal response in
conditions involving premature red cell destruction in the circulation or following blood loss due to acute hemorrhage. The
reticulocyte count is consistently increased in active hemolytic disease because the marrow speeds up red cell production
to supply replacement cells. Anemia develops when the rate of red cell destruction exceeds the marrow's ability to replace
red cells (uncompensated hemolytic disease). The reticulocyte count is not usually elevated in pernicious anemia even
though increased marrow erythropoiesis occurs. The defective cellular maturation that occurs in megaloblastic anemias
results in the death of many red cells in the bone marrow (ineffective
erythropoiesis).
Which of the following conditions is not usually associated with marked reticulocytosis?

A. Four days after a major hemorrhage

B. Drug-induced autoimmune hemolytic anemia
C. Sickle cell anemia
D. Pernicious anemia
B. Membrane cation permeability

B. The major defect in hereditary stomatocytosis is altered permeability of the red cell membrane to Na+ and K+ ions. A
net gain of sodium within the cell leads to increased water entry and the appearance of a swollen cell with a slit-like area
of pallor. This is a heterogeneous group of disorders, in that a number of specific membrane defects have been
postulated, and anemia varies from mild to severe. One autosomal dominant disorder is associated with Rh-null
individuals.
Hereditary stomatocytosis is manifested physiologically by changes in

A. Hemoglobin oxygen affinity

B. Membrane cation permeability
C. Efficiency of hemoglobin reduction
D. Glycolytic ATP production
D. Increased platelets, increased granulocytes, decreased erythropoietin level

D. Polycythemia vera (PV) belongs to the group of disorders that are hematopoietic stem cell defects and commonly
characterized as myeloproliferative disorders. Although the major increase in PV is in red blood cells, there is also an
overproduction of granulocytes and platelets, particularly in the early stages of the disease. The increased production of
red cells in PV is not due to the activity of erythropoietin. The production of erythropoietin is almost completely suppressed
in this malignant condition.
In addition to an increase in red blood cells, which of the following is characteristic of polycythemia vera?

A. Decreased platelets, decreased granulocytes, decreased erythropoietin level

B. Decreased platelets, decreased granulocytes, increased erythropoietin level
C. Increased platelets, increased granulocytes, increased erythropoietin level
D. Increased platelets, increased granulocytes, decreased erythropoietin level
A. Extramedullary hematopoiesis

A. Aplastic anemia can be defined as blood pancytopenia resulting from bone marrow failure. This stem cell disorder
results in a hypocellular marrow with few developing precursors and decreased production of all cell lines. The anemia is
generally normocytic or slightly macrocytic with reticulocytopenia. The "defect" also affects resting hematopoietic cells in
the liver and spleen, so extramedullary hematopoiesis does not occur to compensate for marrow failure
Which of the following is not characteristic of aplastic anemia?

A. Extramedullary hematopoiesis
B. Bone marrow hypoplasia
C. Absolute reticulocytopenia
D. Blood findings of pancytopenia
A. Both normal

A. Because red blood cells and plasma are lost together, the hemoglobin and hematocrit will not reflect the severity of an
acute hemorrhage until the lost blood volume begins to be replaced by the formation of plasma. The restoration of a
normal blood volume is usually complete by 24 hours. It is then that the hemoglobin and hematocrit will reach their lowest
point and will begin to rise only with the release of newly formed red cells, usually within 3-4 days.
What values would you expect to obtain on hemoglobin and hematocrit determinations done immediately after a major
hemorrhage, if hemoglobin and hematocrit values were normal prior to the hemorrhage?

A. Both normal
B. Both decreased
C. Hemoglobin decreased, hematocrit normal
D. Hemoglobin normal, hematocrit decreased
D. No further testing is indicated

D. Elevated RBC, hemoglobin, and hematocrit values in a newborn are a carryover from intrauterine life, when a high
number of red cells were needed to carry oxygen. Erythropoiesis is suppressed in response to the marked increase in
oxygenation of tissues after birth, and the reticulocyte count, which is initially high, will fall along with a slow decline in the
hemoglobin level. A hemoglobin value below 140 g/L (14.0 g/dL) is abnormal for a neonate. Newborn red cells are
macrocytic and up to 10 nucleated red cells per differential may be seen.
Results from a 1-day-old infant include a hemoglobin of 201 g/L (20.1 g/dL), hematocrit of 0.60 L/L (60.0%), MCV of 110.2
fL, and 4 nucleated red cells/100 WBCs. How should these results be interpreted?

A. The elevated hemoglobin and hematocrit values indicate possible dehydration.

B. The nucleated red cells suggest accelerated erythropoiesis due to a hemolytic process.
C. Testing should be done to identify the cause of the macrocytosis.
D. No further testing is indicated.
D. Dacryocytes; myelofibrosis

D. The red blood cells with single elongated projections, seen in Color Plate 7, are dacryocytes or teardrops. Dacryocytes
are often seen in disorders of marrow replacement that affect bone marrow architecture, especially myelofibrosis.
Teardrops can also result from the splenic removal of inclusions and may be present in a variety of anemias.
Drepanocytes or sickle cells are observed during a sickling crisis of sickle cell anemia. Acanthocytes, echinocytes, and/or
codocytes can be found in liver disease (presence varies with disease severity).
When viewing Color Plate 7, the red blood cells with a single elongated projection are known as and may be seen in

A. Acanthocytes; liver disease

B. Echinocytes; liver disease
C. Drepanocytes; myelofibrosis
D. Dacryocytes; myelofibrosis
C. Myelophthisic

C. Myelophthisic anemia is an anemia of bone marrow failure. It is seen in patients who are experiencing bone marrow
replacement of normal hematopoietic tissue by metastatic cancer cells, fibrosis, or leukemia. The anemia is considered a
hypoproliferative anemia because there is no hemolysis involved and the cells are normocytic, normochromic. Disruption
of the bone marrow by abnormal cells can result in the release of immature cells (nucleated red cells and immature
neutrophils) into the blood and may involve blood cell production in extramedullary sites
A patient with normocytic, normochromic anemia secondary to small cell carcinoma may be exhibiting an anemia
designated as

A. Hemolytic
B. Megaloblastic
C. Myelophthisic
D. Sideroblastic
A. Has no identifiable cause

A. Any idiopathic disorder is one for which there is no apparent cause. Ionizing radiation is a well-known cause of aplasia,
as is chemical exposure (pesticides, benzene). latrogenic disorders are those that result from treatments for a different
disorder; for example, aplasia can result from chloramphenicol treatment for bacterial disease. Aplastic anemia may
develop as a complication from infections such as EpsteinBarr or hepatitis viruses.
Idiopathic aplastic anemia is best defined as a form of anemia that

A. Has no identifiable cause

B. Is caused by a physician's treatment
C. Follows exposure to ionizing radiation
D. Develops after a viral infection
C. Diamond-Blackfan anemia

C. Diamond-Blackfan anemia is a congenital disorder that depresses only red blood cell production. Fanconi anemia is a
congenital form of aplastic anemia that results in aplasia of all cell lines and has a high risk of developing acute myeloid
leukemia or other cancers. The bone marrow distinguishes Diamond-Blackfan from the hypocellular marrow seen in
aplastic anemia because there is a lack of erythroid precursors but a normal number of myeloid and megakaryocytic
precursor cells.
Which of the following is a true red blood cell aplasia?

A. Marrow replacement anemia

B. Fanconi anemia
C. Diamond-Blackfan anemia
D. Donath-Landsteiner anemia
C. Dehydration secondary to diuretic use

C. Dehydration is a cause of relative (pseudo) erythrocytosis due to plasma loss. High altitude adjustment, cardiac or
pulmonary disease, and defective oxygen transport are all causes of absolute secondary erythrocytosis. Secondary
erythrocytosis (polycythemia) is a compensatory increase in red cells, produced in an attempt to increase the amount of
oxygen available to the tissues.
Which of the following is not a cause of absolute secondary erythrocytosis?

A. Defective cardiac or pulmonary function

B. High-altitude adjustment
C. Dehydration secondary to diuretic use
D. Hemoglobins with increased oxygen affinity
B. Four gamma chains

B. In infants with homozygous alphathalassemia, no alpha-globin chains are produced (because of the deletion of all four
alpha genes). Consequently, the infants have nearly 100% hemoglobin Bart's, which consists of four gamma-globin
chains. This hemoglobin migrates farther toward the anode than Hb A. Because Hb Bart's has a very high oxygen affinity,
it is useless for delivery of oxygen to the tissues, making its presence incompatible with life. Hemoglobin H, composed of
four beta chains, also migrates farther than Hb A, but Hb H disease is not fatal
A cellulose acetate hemoglobin electrophoresis (alkaline pH), performed on the blood of a stillborn infant, revealed a
single band that migrated farther toward the anode than did the Hb A control. What is the most likely composition of the
stillborn infant's hemoglobin?

A. Four beta chains

B. Four gamma chains
C. Two alpha and two beta chains
D. Two alpha and two gamma chains
C. Hydrops fetalis

C. Bart's hydrops fetalis (homozygous alphathalassemia major) is a lethal condition in which all normal hemoglobins are
absent and the presence of Bart's hemoglobin results in death due to hypoxia. Severe cases of Rh hemolytic disease of
the newborn/fetus (erythroblastosis fetalis) are characterized by hemolytic anemia, high numbers of nucleated red blood
cells, and hyperbilirubinemia that can cause brain damage (kernicterus). The bilirubin level is elevated but anemia is mild,
if present, in ABO hemolytic disease of the newborn.
The most likely cause of the stillborn infant's condition in question 83 is

A. Erythroblastosis fetalis
B. Rh hemolytic disease of the fetus
C. Hydrops fetalis
D. ABO hemolytic disease of the newborn
B. Folic acid and vitamin B12 deficiencies

B. The blood profile alone cannot distinguish folic acid and vitamin B12 deficiencies, because both are characterized by
macrocytic ovalocytes, Howell-Jolly bodies, and hypersegmented neutrophils. Clinical severity generally differentiates the
heterozygous (mild) and homozygous (severe) conditions of thalassemic and sickle cell syndromes. The anemia of acute
blood loss is usually normocytic, whereas the anemia of chronic blood loss becomes microcytic due to the development of
iron deficiency.
Which of the following conditions show similar CBC and blood smear findings?

A. Beta-thalassemia major and minor

B. Folic acid and vitamin B12 deficiencies
C. Acute and chronic blood loss
D. Sickle cell disease and trait

C. Direct antiglobulin test

C. The cause of the many spherocytes and polychromatophilic red cells seen in Color Plate 8 would be best determined
with the direct antiglobulin test (DAT). The differential diagnosis is hereditary spherocytosis (negative DAT) and warm
autoimmune hemolytic anemia (positive DAT). Both of these hemolytic disorders are the result of membrane injury and
would show an increased osmotic fragility result due to the spherocytes, elevated reticulocyte counts, and elevated urine
urobilinogen, as well as elevated serum bilirubin levels.
Which of the following would be useful in identifying the cause of the blood profile seen in Color Plate 8?

A. Osmotic fragility test

B. Reticulocyte count
C. Direct antiglobulin test
D. Urine urobilinogen level
D. Aplastic anemia

D. Schistocytes and spherocytes are associated with red cell destruction and would be found in clostridial septicemia
(toxins), prosthetic heart alves (mechanical trauma), and thermal burns (heat). Microspherocytes can also result from the
direct membrane damage caused by clostridial toxins and heat. Aplastic anemia is not a hemolytic anemia but is caused
by decreased bone marrow production. Aplastic anemia is usually normocytic, with no evidence of red cell damage on the
blood smear, and red cell destruction tests such as serum bilirubin would be normal.
Which of the following conditions is not associated with the presence of schistocytes and spherocytes?

A. Clostridial septicemia
B. Prosthetic heart valves
C. Severe thermal burns
D. Aplastic anemia
D. Relative polycythemia

D. Erythrocytosis (polycythemia) is either absolute or relative. Absolute erythrocytosis occurs when the RBC mass
increases, taking up a larger than usual proportion of the blood volume. Relative polycythemia occurs when the RBC
mass stays normal but the amount of fluid volume decreases, thus increasing the proportion of the blood occupied by red
cells as compared to the total blood volume which has decreased. Primary polycythemia is a condition of erythrocytosis
without an underlying or contributing condition. The body produces an increased number of red cells without an increase
in erythropoietin (an inappropriate response). Secondary polycythemia occurs when some underlying condition causes an
increase in erythropoietin, so erythrocytosis occurs secondary to the condition (an appropriate
response).
A 30-year-old woman who has been vomiting for 3 days has a hemoglobin value of 180 g/L (18.0 g/dL) and a hematocrit
of 0.54 L/L (54.0%). Her results suggest the presence of

A. Absolute erythrocytosis
B. Primary polycythemia
C. Secondary polycythemia
D. Relative polycythemia
A. Hemochromatosis

A. Hemochromatosis is an excessive deposition of iron in body tissues that results in iron-laden macrophages, expansion
of storage sites, and serious damage to organs (heart, liver). Iron overload can be hereditary or acquired as a
complication of severe hemolytic anemias, frequent blood transfusions, or sideroblastic anemia. Hereditary
hemochromatosis is caused by a mutation of the HFE gene that results in increased absorption of iron from the
gastrointestinal tract and leads to iron overload. It is associated with low levels of hepcidin, an iron regulator, which
causes increased iron absorption and release of iron from macrophages. The treatment for hereditary hemochromatosis is
phlebotomy, and molecular
testing is done for diagnosis.
An excessive accumulation of iron in body tissues is called

A. Hemochromatosis
B. Erythroblastosis
C. Megaloblastosis
D. Acrocyanosis
A. Acanthocytes

A. Abetalipoproteinemia, or hereditary acanthocytosis, is a rare autosomal recessive disorder of lipid metabolism. An

absence of serum beta lipoprotein, a transport protein, causes abnormal plasma lipids. The numerous acanthocytes (spur
cells) are the result of an alteration in the lipid content of the red cell membrane. The anemia is mild, but this disorder is
associated with progressive neurologic disease.
Abetalipoproteinemia is characterized by mild anemia and numerous on the peripheral blood smear.

A. Acanthocytes
B. Elliptocytes
C. Echinocytes
D. Stomatocytes
A. Bleeding

A. The majority of body iron is found in the hemoglobin of circulating erythrocytes. This means that any form of bleeding
will lead to excessive iron loss. Iron balance is normally very tightly controlled through absorption rather than excretion.
Iron deficiency in males is rare but, if present, it is usually the result of chronic gastrointestinal bleeding (ulcers, cancer).
What is the most common cause of iron deficiency?

A. Bleeding
B. Gastrectomy
C. Inadequate diet
D. Intestinal malabsorption
B. Decreased alpha chains result in excess beta chains

B. The severe transfusion-dependent anemia, which is typical of homozygous beta-thalassemia, is the result of
unbalanced globin-chain synthesis and massive red cell destruction that far exceeds the rate of production. Decreased or
absent beta chains lead to excess alpha chains that precipitate in red cells and subsequently are destroyed. The
response is intense marrow erythroid hyperplasia, bone expansion, and erythropoiesis in extramedullary sites. A
complication of continuous red cell hemolysis and repeated blood transfusions is iron overload. Patients require iron
chelation therapy to prevent liver and heart failure. Splenectomy may be needed to reduce blood requirements, but it is
not done before 4 years of age because of the increased risk of infection.
Which of the following does not characterize beta-thalassemia major?

A. Transfusion-dependent anemia
B. Decreased alpha chains result in excess beta chains.
C. Iron chelation therapy is necessary.
D. Common in persons of Mediterranean ancestry
A. Serum iron decreased, transferrin decreased

A. Serum iron is low in both iron-deficiency anemia and the anemia of chronic disorders. The total iron-binding capacity
(TIBC), which is an indirect measure of the amount of transferrin protein, is low in the anemia of chronic disease, whereas
it is high in iron deficiency. Synthesis of transferrin is regulated by iron availability. Usually, when storage iron decreases,
serum iron levels decrease and transferrin levels (TIBC) increase. In the anemia of chronic disorders, storage iron is
normal or increased (but unavailable), and transferrin levels (TIBC) are decreased.
In the anemia of chronic disease, what are the usual serum iron and transferrin levels?

A. Serum iron decreased, transferrin decreased

B. Serum iron decreased, transferrin increased
C. Serum iron normal, transferrin normal
D. Serum iron increased, transferrin increased
C. Neurologic system

C. Although the punctate basophilic stippling found in lead poisoning in erythrocytes is considered a classic finding, the
anemia present is usually not severe unless accompanied by iron deficiency. The presence of lead inhibits several
enzymes involved in the formation of heme, with a consequent increase in erythrocyte protoporphyrin and urinary
aminolevulinic acid. The most significant effect of lead toxicity is the resulting neurological deficit and impairment of
mental development.
In children, the most important effect of lead poisoning is on the

A. Liver
B. Kidney
C. Neurologic system
D. Development of erythrocytes
C. Spleen removal

C. In Color Plate 9, the dual population of red blood cells represented may also be termed dimorphic. This blood picture
could be seen in a patient with microcytic, hypochromic anemia after the transfusion of normal red cells or when new
normocytic, normochromic red cells are produced after successful treatment for iron deficiency. Concurrent deficiencies,
such as coexisting iron and folate deficiency during pregnancy, would result in the production of both microcytic and
macrocytic red cells.
Which of the following would not result in the dual population of red cells represented in Color Plate 9?

A. Blood transfusion
B. Oral iron therapy
C. Spleen removal
D. Coexisting deficiencies
B. Substitution of valine for glutamic acid in position 6 of the beta-globin chain

B. The cells visualized in Color Plate 10 are sickle cells in the presence of target cells. The substitution of a valine for the
glutamic acid normally found in the sixth position of the betaglobin chain causes red cells containing hemoglobin S to
undergo the characteristic shape change that gives the sickle cell its name. A defect of both beta genes results in sickle
cell disease, whereas a single gene mutation causes the sickle cell trait. Hemoglobin C results from the substitution of
lysine for glutamic acid in the sixth position of the beta-globin chain.
What is the most likely genetic defect in the hemoglobin of cells seen in Color Plate 10?

A. Substitution of valine for glutamic acid in position 6 of the alpha-globin chain

B. Substitution of valine for glutamic acid in position 6 of the beta-globin chain
C. Substitution of lysine for glutamic acid in position 6 of the alpha-globin chain
D. Substitution of lysine for glutamic acid in position 6 of the beta-globin chain
D. Percentage of hemoglobin S on electrophoresis

D. The number of irreversibly sickled cells (ISCs) and the proportion of S hemoglobin within the cells contribute
collectively to the severity of sickle cell disorders. The classification of "trait" versus "disease" is not based on the severity
of symptoms. The absence of Hb A and the presence of over 80% Hb S on electrophoresis would be classified as
homozygous sickle cell disease (SS), whereas the heterozygous condition (AS) would show approximately 60% Hb A and
40% Hb S. Sickling is rare in the trait condition because of the lower concentration of Hb S. Sickle cell disease typically
shows increased levels of compensatory Hb F, as does hemoglobin SC disease.
On what is the classification of sickle cell trait versus sickle cell disease based?
A. Severity of the clinical symptoms
B. Number of irreversibly sickled cells (ISCs)
C. Level of compensatory hemoglobin F
D. Percentage of hemoglobin S on electrophoresis
B. Supportive therapy

B. Hyperbaric oxygen will reverse the sickling process, but it will also suppress erythropoietin, which stimulates the bone
marrow to produce adequate replacement erythrocytes. Hydroxyurea reduces sickling by increasing Hb F levels and has
been shown to improve the clinical course of patients plagued by painful crises. Treatment is primarily supportive and
symptomatic, with efforts made to avoid those factors known to precipitate a crisis.
Which of the following is the most appropriate treatment for sickle cell anemia?

A. Hydroxyurea
B. Supportive therapy
C. Hyperbaric oxygen
D. Iron
D. Reticulocyte count

D. In response to premature red cell destruction, the normal bone marrow can speed up red cell production. Hemolytic
anemias typically have high reticulocyte counts, because the marrow can respond to the need for red cells. Generally,
anemias caused by defective maturation or decreased production have inappropriately low reticulocyte counts, because
the marrow fails to respond due to injury or lack of essential hematopoietic components. Low hemoglobin and hematocrit
values reveal the presence of anemia but do not indicate etiology. The reticulocyte count is particularly useful in
distinguishing hemolytic anemias from other normocytic anemias that are not hemolytic.
Which of the following values can be used to indicate the presence of a hemolytic anemia?

A. Hemoglobin level
B. Hematocrit level
C. Erythrocyte count
D. Reticulocyte count
C. Heterozygous beta-thalassemia

C. Both iron deficiency and heterozygous thalassemia can present with a mild microcytic, hypochromic anemia. Target
cells may be seen in both, but basophilic stippling is only found in thalassemia. The hemoglobin A2 is normal in
heterozygous alpha thalassemia but is frequently twice the normal level in heterozygous beta-thalassemia, because these
individuals compensate with increased delta-chain production due to deficient beta-globin chain synthesis. In this case,
iron deficiency would likely be ruled out first with iron tests. Beta-thalassemia with hemoglobin S trait (Hb S/beta-
thalassemia) produces a severe clinical picture similar to sickle cell anemia, with sickling of red cells.
A pre-operative, 20-year-old female has a mild microcytic anemia, with target cells and stippled red cells observed on the
blood smear. Her hemoglobin A2 level is quantified at 5%. What do these findings suggest?

A. Iron-deficiency anemia
B. Heterozygous alpha-thalassemia
C. Heterozygous beta-thalassemia
D. Hemoglobin S/beta-thalassemia
D. Precipitation of denatured hemoglobin

D. Oxidative denaturation is the primary mechanism of the hemolytic process. When glucose-6-phosphate dehydrogenase
(G6PD) is deficient, the red blood cells cannot generate sufficient reduced glutathione (GSH) to detoxify hydrogen
peroxide. Hemoglobin is oxidized to methemoglobin, denatures, and precipitates, forming Heinz bodies. The Heinz bodies
cause the rigidity of the red cells, and hemolysis occurs as the cells try to pass through the microcirculation.
What causes the hemolytic process in glucose-6-phosphate dehydrogenase deficiency following oxidant exposure?

A. Coating of red cells by antibody

B. Osmotic pressure changes
C. Complement attachment
D. Precipitation of denatured hemoglobin
B. Higher number of circulating reticulocytes

B. In hereditary spherocytosis, the rigid spherocytes are being destroyed in the splenic microcirculation. Following
splenectomy, the hemoglobin level should rise as the spherocytes circulate longer. Consequently, there is less need for
increased red cell production by the bone marrow, and the number of reticulocytes released into the blood will fall.
Approximately, 30% of platelets are normally sequestered by the spleen, so a transient increase in the platelet count
occurs and red cell inclusions (Howell-Jolly and Pappenheimer bodies), normally pitted out of red cells by the spleen, will
be observed.
In clinically severe hereditary spherocytosis, which of the following findings would not be found post-splenectomy?

A. Rise in the red cell count and hemoglobin level

B. Higher number of circulating reticulocytes
C. Increased number of Howell-Jolly bodies
D. Transient elevation in the platelet count
D. Increased serum haptoglobin

D. Unconjugated bilirubin levels will rise when either excessive intravascular or extravascular hemolysis is occurring.
When hemolysis is intravascular, the free hemoglobin released into the circulation is bound by haptoglobin, and the
complex is transported to the liver, where it is metabolized to bilirubin. Depletion of the haptoglobin protein will occur if use
exceeds production, and then hemopexin binds hemoglobin for removal. When both haptoglobin and hemopexin are
depleted, plasma hemoglobin levels will increase. The serum lactate dehydrogenase rises when red cells are broken
down and intracellular LD enzymes are released.
Which of the following laboratory results is not consistent with accelerated red cell destruction?

A. Increased serum bilirubin

B. Increased plasma hemoglobin
C. Increased serum lactate dehydrogenase (LD)
D. Increased serum haptoglobin
A. Extracorpuscular factors

A. Hemolytic anemias can be classified by the mode of transmission (hereditary or acquired) and by the type of defect
(intrinsic or extrinsic). With the exception of paroxysmal nocturnal hemoglobinuria (PNH), intrinsic defects are hereditary,
and the defect that shortens survival is within the abnormal red cell. Hemolytic anemias due to extrinsic defects are
acquired and caused by external agents or extracorpuscular factors that destroy the intrinsically normal red cell.
Acquired hemolytic anemias are usually due to

A. Extracorpuscular factors
B. Defects within the bone marrow
C. Intracellular factors
D. Changes in hemoglobin stability
C. P antigens

C. Paroxysmal cold hemoglobinuria (PCH) is caused by an IgG biphasic antibody with P specificity known as the Donath-
Landsteiner antibody. This autoantibody fixes complement to the red cells in the cold, and the complementcoated red
cells lyse when warmed. PCH can be idiopathic or follow a viral infection and is characterized by acute intravascular
hemolysis and hemoglobinuria after cold exposure. Cold autoantibodies usually show I specificity, whereas warm
autoantibodies are often directed against Rh antigens on the red cells.
The antibody associated with paroxysmal cold hemoglobinuria shows specificity for

A. ABO antigens
B. I antigens
C. P antigens
D. Rh antigens
B. Vitamin B12

B. The hypersegmented neutrophils and macrocytic ovalocytes seen in Color Plate 11 suggest the presence of
megaloblastic anemia. The two most common causes are lack of folic acid or vitamin Bj2, which are coenzymes required
for normal DNA synthesis. This patient's neurological symptoms are indicative of a vitamin B12 deficiency, because that
vitamin is also needed for myelin synthesis (CNS).
A 69-year-old male is admitted with pallor, mild tachycardia, and difficulty walking because of numbness in the
extremities. His CBC reveals a hemoglobin of 78 g/L (7.8 g/dL), a hematocrit of 0.25 L/L (25.0%), and MCV of 118.5 fL.
This patient's symptoms and the blood findings seen in Color Plate 11 are most suggestive of anemia due to a lack of

A. Folic acid
B. Vitamin B12
C. Vitamin B6
D. Ascorbic acid
B. Serum ferritin level

B. Pappenheimer bodies observed with Wright's stain can be confirmed with the Prussian blue stain and are composed of
iron. The presence of siderotic granules in the red cells is associated with iron overload, and the serum ferritin test, which
reflects the amount of storage iron, would be elevated. The test for parietal cell antibodies can be done to determine the
cause of vitamin B12 deficiency.
A clinical laboratory scientist examined a Wright's stained peripheral smear and saw what appeared to be small, dark-
staining granules in the mature erythrocytes. A second smear was stained with Prussian blue and a positive result was
obtained. Based on this information, which of the following would you expect to be abnormal?

A. Plasma hemoglobin level

B. Serum ferritin level
C. Hemoglobin electrophoresis
D. Test for parietal cell antibodies
D. Production of structurally abnormal hemoglobin variants

D. Hemoglobinopathies are a hereditary group of qualitative disorders in which genetic mutations cause the production of
structurally abnormal globin chains. The three most common variant hemoglobins are Hb S, Hb C, and Hb E, all of which
are due to an amino acid substitution in the beta-globin chain. Hemoglobin C is the second most common hemoglobin
variant, after hemoglobin S, seen in the United States. Thalassemias are characterized by an absent or reduced rate of
globin-chain synthesis.
Hemoglobinopathies are characterized by

A. Absent or reduced rate of globin-chain synthesis

B. Inability to transport and release oxygen to the tissues
C. Inhibition of iron chelation needed for heme biosynthesis
D. Production of structurally abnormal hemoglobin variants
C. Membrane loss and red cell trapping occur in the splenic microcirculation.

C. The structurally abnormal red cells in hereditary spherocytosis (HS) are deficient in spectrin and are abnormally
permeable to sodium. The bone marrow produces red cells of normal biconcave shape, but HS cells lose membrane
fragments and become more spherical as they go through the spleen and encounter stress in the blood circulation. The
membrane defect is accentuated by the passage of red cells through the spleen, where they are deprived of glucose and
are unable to generate sufficient ATP to pump sodium out of the cell. Ultimately, the red cells are trapped and destroyed
in the spleen. The osmotic fragility is increased because of the membrane loss (reduced surface area-to-volume ratio),
and the MCHC value may be increased.
Which of the following statements about hereditary spherocytosis is true?

A. Abnormally shaped cells are produced in the bone marrow.

B. Cells have a decreased mean cell hemoglobin concentration (MCHC).
C. Membrane loss and red cell trapping occur in the splenic microcirculation.
D. Red cell osmotic fragility is decreased.
A. Characteristic oval shape occurs in mature erythrocytes.

A. In hereditary elliptocytosis (HE), the red blood cells show increased permeability to sodium and may have one of
several membrane defects linked to this heterogeneous disorder. These include deficiencies in skeletal proteins such as
protein 4.1 or spectrin. The characteristic oval or elliptical shape is seen only in mature red blood cells, and it occurs in the
circulation when HE red cells cannot return to a normal biconcave shape
Which of the following statements about hereditary elliptocytosis (HE) is true?

A. Characteristic oval shape occurs in mature erythrocytes.

B. Heterogeneous group of disorders linked to Rh-null individuals.
C. Cellular defect involves the lipid composition of the membrane.
D. HE cells are abnormally permeable to calcium.

C. Chronic gastrointestinal blood loss

C. The anemia of chronic disease (ACD) is very common and develops in patients with chronic infections (tuberculosis),
chronic inflammatory disorders (rheumatoid arthritis, systemic lupus), and malignant disease (cancer, lymphoma). ACD
has a complex etiology that includes impaired release of storage iron for erythropoiesis and a reduced response to
erythropoietin. The anemia may be normocytic or microcytic, and severity depends on the underlying disorder.
Which of the following disorders is not commonly linked to the development of anemia of chronic disease?

A. Persistent infections
B. Noninfectious inflammatory disorders
C. Chronic gastrointestinal blood loss
D. Malignancy
A. Electrophoresis shows approximately 60% hemoglobin A and 40% hemoglobin C

A. Hemoglobin C disease results from a homozygous substitution of lysine for glutamicacid at position 6 of the beta-globin
chains. Numerous target cells and occasional intracellular C crystals will be found on the blood smear. Osmotic fragility is
decreased (increased resistance) because of the many target cells, and electrophoresis will show an absence of Hb A
and over 90% Hb C. The clinical severity of Hb CC is mild as compared to Hb SS or Hb SC diseases.
Which of the following statements about hemoglobin C disease is false?

A. Electrophoresis shows approximately 60% hemoglobin A and 40% hemoglobin C.

B. Target cells are frequently seen on peripheral smears.
C. Red cells may contain bar-shaped intracellular crystals.
D. The disorder is less severe than sickle cell disease.
D. Increased sickling occludes vessels.

D. Red cells that contain a high concentration of hemoglobin S will assume the sickle shape when deprived of oxygen
(which can be reversed if reoxygenated). After repeated sickling, reversion capabilities are lost and irreversibly sickled
cells (ISCs) are seen. Sickle cells are mechanically brittle, nondeformable cells that become impeded in circulation,
causing blocks that restrict blood flow in vessels and leading to organs (vascular occlusive disease). They are easily
trapped in the small vessels of the spleen, leading to obstructive ischemia and eventual destruction of splenic tissue
Which of the following is associated with sickle cells?

A. Increased oxygen tension promotes sickling.

B. There is decreased mechanical fragility.
C. There is increased deformability.
D. Increased sickling occludes vessels.
B. Aplastic anemia

B. Aplastic anemia is bone marrow failure characterized by hypocellularity and decreased production of all cell lines. The
normal M:E ratio (4:1) does not change in aplasia, because the number of both myeloid and erythroid precursors is
decreased. In anemias such as sickle cell anemia, beta-thalassemia major, or megaloblastic anemia, the marrow
becomes hypercellular because of an increase in erythroid precursors, and the M:E ratio falls.
A bone marrow M:E ratio of 4:1 would bean expected finding for

A. Sickle cell anemia

B. Aplastic anemia
C. Beta-thalassemia major
D. Megaloblastic anemia
B. Secondary warm autoimmune hemolytic anemia

B. The immune hemolytic anemia indicated by the smear findings is warm autoimmune hemolytic anemia (WAIHA).
Antibody-coated red cells are being partially phagocytized by macrophages (with receptors for IgG and complement),
causing loss of membrane fragments. The spherocytes are ultimately destroyed, primarily in the spleen. The cause of the
autoantibody production may be unknown (idiopathic), develop secondary to a disease that alters the immune response
(chronic lymphocytic leukemia or lymphoma), or can be drug induced. Cold hemagglutinin disease is characterized by red
cell agglutination due to a cold autoantibody.
An elderly man with a 10-year history of chronic lymphocytic leukemia presented with jaundice and fatigue that was
attributed to a recent 3-gram drop in his hemoglobin. Many spherocytes and polychromatophilic red cells were found on
his Wright's stained blood smear. Which type of immune hemolytic anemia is most likely?

A. Idiopathic warm autoimmune hemolytic anemia

B. Secondary warm autoimmune hemolytic anemia
C. Primary cold hemagglutinin disease
D. Paroxysmal cold hemoglobinuria
C. Bone marrow erythroid precursors exhibit normoblastic maturation.

C. Intrinsic factor is a glycoprotein secreted by the parietal cells, along with HC1, that is needed to bind vitamin B12 for
absorption. Pernicious anemia (PA), which is a megaloblastic anemia caused by the lack of intrinsic factor, is most
common cause of vitamin B12 deficiency (cobalamin). PA is characterized by atrophy of the gastric parietal cells and
achlorhydria (absence of HC1). Autoimmune factors are involved because a high percentage of patients produce
autoantibodies to intrinsic factor (50%) and/or parietal cells (90%). The bone marrow erythroid precursors exhibit
megaloblastic maturation, with nuclear maturation lagging behind cytoplasmic maturation (asynchrony is also seen in
developing granulocytes and platelets). Many fragile red cells die in the bone maiTow, and those released into the
circulation have a very short survival, which causes a marked increase in lactate dehydrogenase levels.
A moderately anemic patient with suspected pernicious anemia (PA) shows intrinsic factor antibodies and a low
cobalamin level. Which of the following would not support the diagnosis of PA?

A. Gastric atrophy and achlorhydria

B. Oval macrocytes and Howell-Jolly bodies
C. Bone marrow erythroid precursors exhibit normoblastic maturation.
D. Elevated serum lactate dehydrogenase (LD) and bilirubin levels
B. Hemoglobin D

B. Hemoglobin D migrates in the same location as hemoglobin S on cellulose acetate at alkaline pH but does not cause
sickling. The negative solubility test rules out the presence of hemoglobin S. Target cells are seen in large numbers in
homozygous hemoglobin D disease. The quantification of 95% differentiates homozygous from heterozygous states
where less than 50% hemoglobin D would be seen.
A cellulose acetate electrophoresis revealed a large band of hemoglobin in the hemoglobin S position. This band
quantified at 95%. The peripheral smear revealed 70% target cells, and the solubility test was negative. Based on this
information, what is the hemoglobin?

A. Hemoglobin C
B. Hemoglobin D
C. Hemoglobin E
D. Hemoglobin S
B. Glucose-6-phosphate dehydrogenase

B. G6PD deficiency compromises the ability of the glutathione reduction pathway to prevent the oxidation of hemoglobin.
Oxidative stress may occur from infections, ingestion of mothballs, ingestion of fava beans, and certain drugs, including
primaquine or sulfonamides. The oxidized hemoglobin precipitates in the form of Heinz bodies, which leads to a hemolytic
crisis characterized by intravascular red cell destruction, removal of Heinz bodies by splenic macrophages, and the
presence of spherocytes and fragmented red cells on the smear.
A previously healthy man experiences weakness and hemoglobinuria after taking the antimalarial agent primaquine. This
hemolytic attack most likely occurred because of a deficiency of

A. Pyruvate kinase
B. Glucose-6-phosphate dehydrogenase
C. 2,3-Bisphosphoglycerate
D. Methemoglobin reductase
B. Paroxysmal nocturnal hemoglobinuria

B. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired defect of membrane structure in which red cells have a
high affinity for
complement binding. PNH is characterized by pancytopenia and chronic intravascular hemolysis with hemoglobinuria and
hemosiderinuria. A
stem cell mutation causes production of red cells, white cells, and platelets that are sensitive to complement lysis because
of the loss of a membrane glycolipid (GPI). The sucrose hemolysis test can be used to screen for PNH red cells, but the
Ham's acid serum test has been replaced by immunophenotyping for confirmation of PNH. Paroxysmal cold
hemoglobinuria (PCH) is characterized by intravascular hemolysis and hemoglobinuria after cold exposure that is due to a
complement-binding autoantibody. A transient finding of hemoglobinuria following forceful contact of the body with hard
surfaces (as may be seen in joggers and soldiers) describes March hemoglobinuria.
Which of the following is an acquired red cell membrane defect that results in increased sensitivity to complement
binding?

A. March hemoglobinuria
B. Paroxysmal nocturnal hemoglobinuria
C. Paroxysmal cold hemoglobinuria
D. Methemoglobinemia
A. Methotrexate therapy

A. Secondary, acquired sideroblastic anemia is the result of blocks in the protoporphyrin pathway that can be identified
and, therefore, are reversible if the toxin or agent is removed. Alcohol inhibits vitamin B6 and anti-tuberculosis drugs also
interfere with vitamin B6 (pyridoxine). Lead poisoning causes multiple blocks in protoporphyrin synthesis, including
inhibition of ferrochelatase, which is needed for iron incorporation into protoporphyrin to produce heme. Methotrexate is
an antifolate chemotherapeutic agent that causes a drug induced megaloblastic anemia.
Which of the following is not associated with acquired reversible sideroblastic anemias?

A. Methotrexate therapy
B. Lead intoxication
C. Isoniazid treatment for tuberculosis
D. Acute alcohol ingestion
A. It is due to a reduction in the number of erythrocytes.

A. Although iron deficiency may be the most common cause of anemia in pregnancy, there is a mild form of anemia that
develops during the third trimester in pregnant women with adequate iron levels. Although both erythrocytes and plasma
increase during pregnancy, the plasma increases in a higher proportion, causing a relative (pseudo) anemia. This
increased blood volume actually increases oxygen delivery to both the mother and the fetus.
Which of the following statements about the relative anemia of pregnancy is false?

A. It is due to a reduction in the number of erythrocytes.

B. It is normocytic and normochromic.
C. It does not produce an oxygen deficit for the fetus.
D. It is associated with an increase in plasma volume.
A. Loss of erythropoietin synthesis

A. The anemia of chronic renal failure results from decreased production and release of erythropoietin from the diseased
kidney. The drop in erythropoietin results in decreased red blood cell production by the marrow. Recombinant
erythropoietin is of great value in treating anemia resulting from end-stage renal disease. Iron or folate supplements may
be needed to maximize the response, especially in patients on dialysis. Uremic metabolites may cause reduced red cell
survival and impairment of platelet function.
The anemia found in chronic renal failure is most likely caused by

A. Loss of erythropoietin synthesis

B. Lack of cellular oxygen demand
C. Defective iron absorption
D. Destruction of red cells by uremic metabolites
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D. Reduced red cell survival

D. Aplastic anemia is a stem cell defect that leads to decreased production of erythrocytes, leukocytes, and platelets
(pancytopenia). The survival of red cells released into the circulation is normal. Infection is a serious problem because of
the lack of neutrophils. The reduced number of platelets is responsible for the bleeding often seen. Treatment includes
blood and platelet transfusions, antibiotics, growth factors, and steroids. Bone marrow transplantation may be necessary.
Which of the following phrases about aplastic anemia is false?

A. Stem cell disorder

B. Risk of life-threatening infection
C. Frequent bleeding complications
D. Reduced red cell survival
B. Macrocytic anemia

B. The fish tapeworm competes for vitamin B12, and a macrocytic (megaloblastic) anemia may develop. Hookworm
infestation causes chronic blood loss and a microcytic anemia due to iron deficiency. A variety of organisms are
associated with hemolysis, including malaria and clostridial infections. Viral hepatitis can cause marrow suppression and a
normocytic, hypoproliferative anemia.
The fish tapeworm Diphyllobothrium latum is associated with the development of

A. Microcytic anemia
B. Macrocytic anemia
C. Hemolytic anemia
D. Hypoproliferative anemia
A. Renal tumors

A. A need for the increased oxygen carrying capacity provided by additional red blood cells is found in conditions such as
pulmonary disease, where normal oxygenation is inhibited. A decrease in the ability of the cardiovascular system to
appropriately circulate cells is another reason for increased erythrocytes. Individuals with a high level of methemoglobin,
such as heavy smokers or persons with genetic disorders, cannot effectively unload oxygen. This results in a need for
increasing the number of red blood cells to compensate. Renal tumors are associated with excess production of
erythropoietin, leading to an inappropriate polycythemia
An increase in erythropoietin is not a normal compensating mechanism in which of the following conditions?

A. Renal tumors
B. Heavy smoking
C. Cardiovascular disease
D. Pulmonary disease
B. Quantitative defect in globin-chain synthesis

B. Thalassemias are a group of congenital disorders characterized by quantitative defects in globin-chain synthesis.
Alpha-thalassemias result from gene deletions that cause a reduced rate of alpha-globin chain production. Beta-
thalassemias result from point mutations that cause a reduced rate of beta-globin chain synthesis. Normally, equal
amounts of alpha- and beta-globin chains are produced for Hb A synthesis. In alpha- or betathalassemias, synthesis of
globin chains is imbalanced, because a decreased production rate of one type of globin chain causes an excess of the
other (consequences will depend on the thalassemia type).
Thalassemias are the result of a

A. Structural defect in the heme portion of hemoglobin

B. Quantitative defect in globin-chain synthesis
C. Qualitative defect in globin-chain structure
D. Change in hemoglobin solubility properties
C. Increased serum transferrin, decreased transferrin saturation, decreased ferritin

C. Low serum iron and iron stores (represented by serum ferritin) characterize iron deficiency that is severe enough to
result in anemia. The production of transferrin, the iron transport protein, increases as iron stores decrease. Transferrin
saturation decreases dramatically so that transferrin is less than 15% saturated with iron.
Which of the following characterizes iron deficiency
anemia?

A. Decreased serum iron, decreased transferrin saturation, normal ferritin

B. Decreased serum transferrin,
decreased transferrin saturation, decreased ferritin
C. Increased serum transferrin, decreased transferrin saturation, decreased ferritin
D. Increased serum transferrin, increased transferrin saturation, decreased serum iron
D. By 6 months of age

D. The switch from gamma-globin chain production for Hb F to beta-globin chain synthesis for Hb A occurs 3-6 months
after birth. Clinical symptoms of a homozygous beta-globin chain defect, such as sickle cell disease or homozygous beta-
thalassemia, will not be evident until about 6 months of age or shortly after. Alphaglobin chain production is normally high
throughout fetal and adult life. A homozygous defect involving the alpha-globin chain will affect the infant in utero.
Clinical manifestations of a homozygous mutation involving the beta-globin gene will most likely appear

A. During embryonic development

B. In the neonate at birth
C. No later than 3 weeks after birth
D. By 6 months of age
A. Release of merozoites from erythrocytes

A. The hemolytic crisis of malaria results from the rupture of erythrocytes containing merozoites. This event becomes
synchronized to produce the fever and chill cycles that are characteristic of this infection. In severe infections, particularly
those caused by Plasmodium falciparum, the massive intravascular hemolysis results in significant hemoglobinuria.
The hemolysis associated with infection by malaria organisms is due to the
A. Release of merozoites from erythrocytes
B. Invasion of erythrocytes by merozoites
C. Host's immunologic response to infected erythrocytes
D. Toxins produced by the malarial organism
D. Crenated cells caused by incorrect blood to anticoagulant ratio

D. The incorrect ratio of blood to anticoagulant caused the cells to shrink. This produced the crenated appearance of the
red cells. This is an artifact as opposed to a significant clinical finding and can also be the result of prolonged blood
anticoagulation. Spur cells (or acanthocytes) lack a central pallor area and have sharp projections, as opposed to
crenated cells (or echinocytes), which have a pallor area and blunt projections.
A clinical laboratory scientist received a 5 mL EDTA tube that contained 0.5 mL of anticoagulated blood. A smear was
prepared and stained with Wright's stain. When examined microscopically, the majority of cells appeared to have many
evenly distributed, blunt spicules on the surface. How should this cellular appearance be interpreted?

A. An anemic condition requiring further testing

B. Spur cells caused by using incorrect technique during slide preparation
C. Artifact caused by a dirty spreader slide
D. Crenated cells caused by incorrect blood to anticoagulant ratio
A. Pyruvate kinase deficiency

A. Pyruvate kinase (PK) is an enzyme of the Embden-Meyerhof pathway (anaerobic glycolysis). A deficiency of PK results
in decreased ATP generation, which causes impairment of the cation pump and a loss of normal membrane deformability.
PK-deficient cells have a shortened survival time, but clinical manifestations vary widely.
A failure to generate sufficient ATP is characteristic of red blood cells with

A. Pyruvate kinase deficiency

B. Glucose-6-phosphate dehydrogenase deficiency
C. Lipoprotein deficiency
D. Hexokinase deficiency
B. Iron stores are depleted

B. When iron use exceeds absorption, iron stores (serum ferritin) are depleted first. At this early stage, there is no anemia
(normal hemoglobin) and the transferrin level is normal. This is followed by increased transferrin synthesis (TIBC) and
decreased serum iron. Finally, a microcytic, hypochromic anemia develops
When iron use exceeds absorption, which of the following occurs first?

A. Hemoglobin level decreases.

B. Iron stores are depleted
C. Transferrin synthesis increases.
D. Excretion of iron decreases.
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A. Impaired release of storage iron because of increased hepcidin levels

A. In the anemia of chronic disease (ACD), a chronic illness causes impaired release of iron from storage. These patients
have iron but are unable to use it for bone marrow erythropoiesis. Hepcidin, a hormone produced by the liver, plays a
major role in the regulation of body iron by influencing intestinal absorption and release of storage iron from macrophages.
Hepcidin levels increase during inflammation (positive acutephase reactant), which causes decreased release of iron from
stores. There is also impaired response of marrow red cell precursors to erythropoietin stimulation in ACD. The impaired
response is thought to be related to the effects of inflammatory cytokines. Recombinant erythropoietin improves the
anemia in some cases.
The major mechanism responsible for the anemia of chronic disease is

A. Impaired release of storage iron because of increased hepcidin levels

B. Damaged bone marrow stem cells
C. Immune destruction caused by red cell autoantibodies
D. Increased erythropoietin response by committed red cell progenitor cells
C. Reversible with intramuscular vitamin B12 injections

C. In the idiopathic or primary type of sideroblastic anemia, the blocks in the protoporphyrin pathway (heme synthesis)
that lead to iron overload are unknown and, therefore, are irreversible. The anemia is refractory (unresponsive) to
treatment other than transfusion. Ringed sideroblasts and increased stainable iron will be found in the bone marrow when
stained with Prussian blue. This primary, acquired form of sideroblastic anemia is also known as refractory anemia with
ringed sideroblasts (RARS) and is classified as a myelodysplastic syndrome.
Which of the following is not a characteristic of the idiopathic type of sideroblastic anemia?

A. Refractory to treatment
B. Blocks in heme synthesis are unknown
C. Reversible with intramuscular vitamin B12 injections
D. Subtype of myelodysplastic syndromes
B. Result of hyperplastic marrow activity

B. The demand for red blood cell replacement in beta-thalassemia major during early childhood development results in a
hyperproliferative marrow. Expansion of the marrow causes the bones to be thin and narrow. This may result in pathologic
fractures. Facial bones have the Mongoloid appearance, with prominence of the forehead, cheekbones, and upper jaw.
Thinning of bones and deformation of facial bone structure seen in homozygous beta-thalassemia is a

A. Consequence of disturbances in calcium metabolism

B. Result of hyperplastic marrow activity
C. Secondary disorder due to immunologic response
D. Result of increased fibroclast activity
D. The autoantibody is usually an IgG type directed against Rh antigens.

D. Cold autoimmune hemolytic anemia (CAIHA), or cold hemagglutinin disease, is characterized by the production of IgM
cold autoantibodies that often show I specificity. The cause of the autoantibody production may be unknown (primary) or
occur secondary to Mycoplasma pneumonia or lymphoma. Significantly high liters can result in agglutination of red cells in
the extremities called Raynaud's phenomenon (acrocyanosis).
Which of the following does not accurately describe cold autoimmune hemolytic anemia?

A. Red cell agglutination in extremities induces Raynaud's phenomenon.

B. It may occur secondary to Mycoplasma pneumonia.
C. Hemolysis is complement-mediated or via removal of coated cells.
D. The autoantibody is usually an IgG type directed against Rh antigens.
A. Sickle cell disease during crisis

A. The red blood cell distribution width (RDW)

is an index of red cell size variation or anisocytosis.
The RDW will be high when a heterogeneous cell population consisting of red cells with varying sizes is present (sickle
cell anemia with compensation). The RDW is low when a homogeneous or single population of red cells is present that
are of uniform size (thalassemia minor, anemia of chronic disease).
Which of the following represents an anemia that would have a high red cell distribution width (RDW)?

A. Sickle cell disease during crisis

B. Thalassemia minor
C. Aplastic anemia
D. Anemia of chronic disorders
D. Folic acid deficiency

D. Splenomegaly is a common finding in hemolytic anemias, because the spleen is the major site of extravascular red cell
destruction. Patients with hereditary spherocytosis and hemoglobin SC disease often have enlarged spleens for this
reason. Patients with beta-thalassemia major exhibit splenomegaly because of active splenic removal of red cells, but the
spleen may also be a site of extramedullary erythropoiesis. Splenomegaly can also be due to extramedullary
hematopoiesis in malignant disorders such as polycythemia vera or myelofibrosis. Splenomegaly would not be a
characteristic finding in megaloblastic anemia.
In which of the following disorders would splenomegaly not be a common finding?

A. Homozygous beta-thalassemia
B. Hereditary spherocytosis
C. Hemoglobin SC disease
D. Folic acid deficiency

C. Phagocytes, immunocytes
C. The major function of leukocytes is defense, either by phagocytosis or by immune mechanisms. The phagocytic cells
are the granulocytes and monocytes. The immune response is mediated by lymphocytes; however, monocytes play a role
in immunity as antigen-presenting cells. Leukocytes may be classified according to granularity as granulocytes and
nongranulocytes or divided based on nuclear segmentation as polymorphonuclears (PMNs) and mononuclears
Functionally, white blood cells are divided into

A. Granulocytes, nongranulocytes
B. Polymorphonuclears, mononuclears
C. Phagocytes, immunocytes
D. Granulocytes, lymphocytes
D. Monocyte

D. Monocytes have a diameter up to 20 making them the largest cells in the peripheral
blood under normal conditions. Eosinophils and neutrophils have diameters of about 12 |xm. The small lymphocyte is 8-9
|xm in diameter, similar to the red blood cell, which has a diameter of 6-8 (xm. Large lymphocytes range in size from 11 to
16 jim in diameter.
What is the largest white blood cell normally found in the peripheral blood?

A. Eosinophil
B. Neutrophil
C. Lymphocyte
D. Monocyte
A. Less than 1 day

A. After granulocytes are released from the bone marrow, they remain in the circulation one day or less. Their major
function takes place in the tissues. They migrate through the vessel walls to reach areas of inflammation very soon after
release. The life span of the granulocyte is short; however, eosinophils and basophils appear to survive longer in the
tissues than neutrophils.
What is the approximate amount of time a granulocyte spends in the circulation before migrating into the tissues?

A. Less than 1 day

B. About 3 days
C. Up to 5 days
D. More than 10 days
C. 50%

C. Approximately 50% of the neutrophils in the peripheral blood are found in the circulating pool. This is the pool
measured when a total WBC count is done. Another 50% are found adhering to vessel walls (marginal pool). These pools
are in constant exchange. Emotional or physical stimuli can cause a shift of cells from the marginating pool to the
circulating pool, causing a transient rise in the total WBC count. The total WBC count can double but returns to normal
within several hours
What percentage of neutrophils in the peripheral blood constitutes the circulating pool?

A. 100%
B. 80%
C. 50%
D. 30%
A. Neutrophil

A. Although some phagocytic activity has been attributed to the eosinophil, it is the segmented neutrophil and monocyte
that have the greatest phagocytic activity. The neutrophil is the most important because of numbers and its ability to
respond quickly, especially against bacterial pathogens. Monocytes arrive at the site of injury after the neutrophil to "clean
up."
What is the major phagocytic cell involved in the initial defense against bacterial pathogens?

A. Neutrophil
B. Eosinophil
C. Basophil
D. Monocyte
B. Colony stimulating factor

B. The growth factor mainly responsible for regulating

the production of granulocytes and monocytes is granulocyte/monocyte colony stimulating factor (GM-CSF), which acts
on the committed bipotential progenitor cell CFU-GM (colonyforming unit GM). GM-CSF stimulation of granulocyte or
monocyte production increases in response to need and can also affect the production of erythrocytic and megakaryocytic
lineages. G CSF induces granulocyte differentiation, and M-CSF supports monocyte differentiation. Erythropoietin (EPO)
is a lineage-specific growth factor responsible for stimulating erythrocyte production, and thrombopoietin (TPO) is mainly
responsible for regulating platelet production. Interleukins, particularly IL-3, influence multiple cell lines,
including granulocytes and monocytes.
What is the growth factor that is primarily responsible for regulating granulocyte and monocyte production?

A. Erythropoietin
B. Colony stimulating factor
C. Interleukin
D. Thrombopoietin
A. Myeloblasts and promyelocytes

A. The granulocyte mitotic pool contains the cells capable of division, which are the myeloblasts, promyelocytes, and
myelocytes. The post-mitotic pool, or reserve, is the largest bone marrow pool and contains metamyelocytes, band and
segmented forms. This pool is available for prompt release into the blood if needed (e.g., infection), and its early release
is the cause of a "left shift." If released, the bone marrow mitotic pool can dramatically increase its activity to replenish this
reserve (cytokine stimulation increases).
What does the granulocyte mitotic pool in the bone marrow contain?

A. Myeloblasts and promyelocytes

B. Band and segmented forms
C. The majority of marrow granulocytes
D. Myelocytes and metamyelocytes
B. An increase in immature blood cells following release of bone marrow pools

B. A "shift to the left" means an increase in immature neutrophilic cells in the blood caused by bone marrow release of
cells in response to infection or tissue damage. A redistribution of the blood pools because of emotional or physical stimuli
is characterized by an increased WBC count without a left shift. A cell "hiatus" refers to a population of cells in which there
is a gap in the normal maturation sequence. A cell hiatus is most often seen in acute leukemia, in which there are many
blasts and a few mature cells but no intermediate stages.
A "shift to the left," when used to describe a cell population, refers to

A. Increased cells in the blood due to a redistribution of blood pools

B. An increase in immature blood cells following release of bone marrow pools
C. A cell production "hiatus" or gap
D. A higher percentage of lymphocytes than neutrophils
D. Decreased numbers of granulocytes

D. "Agranulocytosis" refers to an absence of granulocytes in both the peripheral blood and bone maiTow. A deficiency of
granulocytes is found in cases of aplastic anemia, in which deficiencies in red cells and platelets also occur. The early
release of cells from the bone marrow will result in immature cells in the blood but is not referred to as agranulocytosis.
Neutrophils that exhibit little or no granulation may be called hypogranular or agranular and are a sign of abnormal growth
(dyspoiesis).
Which of the following is characteristic of agranulocytosis?

A. Neutrophils without granules

B. Decreased numbers of granulocytes, red cells, and platelets
C. Immature granulocytes in the peripheral blood
D. Decreased numbers of granulocytes
B. Synthesize antibody

B. Antibodies are synthesized by plasma cells, which are end-stage B lymphocytes that have transformed to plasma cells
following stimulation by antigen. An end product of T cell activation is the production of cytokines (lymphokines) such as
interleukins and colony-stimulating factors. T cells are surveillance cells that normally comprise the majority (about 80%)
of lymphocytes in the blood. T cells regulate the immune response by helping (T helper or inducer cells) or suppressing (T
suppressor cells) the synthesis of antibody by plasma cells.
Which of the following is not a characteristic of T lymphocytes?

A. Secrete cytokines
B. Synthesize antibody
C. Comprise majority of cells in the blood lymphocyte pool
D. Regulate the immune response
C. There is a relative lymphocytosis.

C. Absolute values for cell types are obtained by multiplying the percentage of the cell type by the total number of cells. In
this case, 4000/mm3 X 0.65 = 2600/jJiL or 2.6 X 109/L. Although reference ranges vary, the normal absolute count for
lymphocytes is from 1.0 to 4.0 X 109/L and the normal percentage of lymphocytes is 20-44%. In this case, there is a
relative lymphocytosis (increase in percentage), but the absolute lymphocyte value is normal. Percentages can be
misleading, so the absolute number of a particular cell type should always be evaluated.
An adult has a total white blood cell count of 4.0 X 109/L (4.0 X 103/uL). The differential count is as follows:
polymorphonuclear
neutrophils (PMNs) 25%, bands 5%, lymphocytes 65%, and monocytes 5%. The absolute value reference range for
lymphocytes is 1.0—4.0 X 109/L. Which of the following is true?

A. The percentage of lymphocytes is normal.

B. There is an absolute lymphocytosis.
C. There is a relative lymphocytosis.
D. There is both an absolute and a relative lymphocytosis.
B. Auer rods are composed of fused primary granules.

B. Auer rods are seen in the cytoplasm of malignant cells, most often myeloblasts, and are composed of fused primary
(nonspecific, azurophilic) granules. Hypersegmented neutrophils have five lobes or more and are associated with vitamin
B12 or folate deficiency. Toxic granules are primary granules with altered staining characteristics that stain in late-stage
neutrophils due to toxicity. Dohle bodies are agranular patches of RNA present in neutrophil cytoplasm and associated
with toxic states.
Which of the following statements is correct?

A. Hypersegmented neutrophils have four nuclear lobes.

B. Auer rods are composed of fused primary granules.
C. Toxic granules are prominent
secondary granules.
D. Dohle bodies are agranular patches of DNA.
D. Sex

D. The total white blood cell count reference ranges for males and females are equivalent. WBC counts do change with
age, being higher in newborns and children than in adults. Any change from basal conditions, such as exercise or
emotional stress, will cause a transient leukocytosis due to a redistribution of blood pools. WBC values are lower in the
morning and higher in the afternoon (diurnal variation).
Which of the following factors is not associated with variations in the total white blood cell count?

A. Age
B. Exercise
C. Emotional stress
D. Sex
C. Risk of infection

C. Neutropenia is associated with a risk of infection. The degree of neutropenia correlates with the infection risk from high
susceptibility (<1.0 X 109/L) to great risk (<0.5 X 109/L). Infection increases with the degree and duration of the
neutropenia. Shortness of breath and bleeding tendencies are clinical symptoms associated with severe anemia and
thrombocytopenia, respectively.
Of the following, an absolute neutrophil count of 1.0 X 109/L would be associated with

A. Shortness of breath
B. Bleeding tendencies
C. Risk of infection
D. No clinical symptoms
B. Membrane receptors bind IgG, initiating anaphylactic reactions.

B. Basophils and tissue mast cells have receptors for IgE and complement components, which trigger degranulation when
appropriate antigens are present and are responsible for severe hypersensitivity reactions (anaphylaxis). Basophils and
tissue mast cells have morphologic similarities but represent distinct cell types. Basophils possess water-soluble granules
that contain, among other substances, heparin and histamine (a vasodilator and smooth muscle contractor). Basophils
have a segmented nucleus, and the granules, although often scanty, overlie the nucleus. The mast cell has a single round
nucleus, contains many more granules than the basophil, and can be found in the bone marrow.
Which of the following statements about basophils is false?

A. Morphologically, basophils resemble tissue mast cells.

B. Membrane receptors bind IgG, initiating anaphylactic reactions.
C. Basophilic granules contain heparin and histamine.
D. Granules are water soluble.
C. Myelocyte

C. The last stage in the granulocytic series that divides is the myelocyte. Cells before and including this stage constitute
the bone marrow mitotic pool and undergo multiple cellular divisions. Nuclear chromatin progressively clumps and nucleoli
are no longer present in the nondividing metamyelocyte stage that follows the myelocyte.
The most mature granulocyte precursor that can undergo mitosis is the

A. Myeloblast
B. Promyelocyte
C. Myelocyte
D. Metamyelocyte
C. Myelocyte

C. The precursor cell that can first be recognized as granulocytic is the myeloblast and has no granules. Primary or
nonspecific granule production begins and ends during the promyelocyte stage. The granules are distributed between
daughter cells as mitotic divisions occur. Secondary or specific granule production begins with the myelocyte stage and
continues during succeeding cell stages with the synthesis of products specific to the function of the particular granulocyte
(neutrophil, eosinophil, or basophil)
Production of primary granules ceases and production of secondary granules commences with what cell stage?

A. Myeloblast
B. Promyelocyte
C. Myelocyte
D. Metamyelocyte
B. Eosinophilic granules contain
lysozyme

B. Eosinophils lack lysozyme, which is present in neutrophils and monocytes, and contain a distinctive peroxidase that
differs biochemically from the myeloperoxidase of neutrophils and monocytes. Major basic protein is a component of the
granules and is very important to the ability of eosinophils to control parasites. In addition, eosinophils play a role in
modifying the allergic reactions caused by degranulation of basophils. Basophils release eosinophil chemotactic factor of
anaphylaxis (ECF-A), which calls eosinophils to the site.
Which of the following statements about eosinophils is false?

A. They contain a type of peroxidase that is distinct from that of neutrophils.

B. Eosinophilic granules contain lysozyme
C. Eosinophils are an important line of defense against parasites.
D. Major basic protein is a component of eosinophil granules.
A. Coated with a phospholipid membrane

A. Primary granules, which appear in the promyelocyte stage, may be called azurophilic or nonspecific granules. Specific
or secondary granules (neutrophilic, eosinophilic, basophilic) appear in the myelocyte stage. Primary granules contain
hydrolytic enzymes (e.g., myeloperoxidase, lysozyme, acid phosphatase) and are coated with a phospholipid membrane.
Lactoferrin is a component of neutrophil granules. Primary granules are visible in the myelocyte stage, but in later stage
cells the primary granules, although present, are less visible by light microscopy under normal conditions.
Which of the following is characteristic of primary granules?

A. Coated with a phospholipid membrane

B. Called azurophilic or specific granules
C. Contain myeloperoxidase and lactoferrin
D. Present in the promyelocyte stage only
A. Toxic granules and Dohle bodies in the neutrophils
A. The presence of toxic granules, Dohle bodies, and/or vacuoles in the cytoplasm of neutrophils (segmented, band,
metamyelocyte, and myelocyte stages) is indicative of a neutrophilic response to inflammation. The changes observed in
the "toxic" neutrophil may occur in patients with severe burns, some malignancies, exposure to toxic drugs and chemicals,
and acute infection (most often bacterial). A Barr body is a "drumstick"-shaped body of nuclear material found in the
neutrophils of females that represents the inactive X chromosome and is of no significance. Auer rods are seen in
malignant myeloid cells, usually blasts. Hypersegmented neutrophils are associated with megaloblastic anemias but may
be seen in long-term chronic infections. Pyknotic cells and vacuoles may be seen in overwhelming sepsis or in a
degenerating blood specimen. Russell bodies are globular inclusions found in plasma cells that are composed of
immunoglobulin.
Which of the following are indicators of a neutrophilic response to tissue damage or inflammatory stimuli?

A. Toxic granules and Dohle bodies in the neutrophils

B. Vacuoles and Barr bodies in the neutrophils
C. Hypersegmented neutrophils and Auer rods
D. Pyknotic neutrophils and Russell bodies
A. Diapedesis

A. Diapedesis is the movement of cells (usually referring to neutrophils) from the blood stream into the tissues by
squeezing through endothelial cells of the vessel wall. Chemotaxis is the movement of cells directed by chemotactic
stimuli such as bacterial products, complement components, or injured tissue. Opsonization is the coating of an organism
or foreign particle by IgG or complement for recognition and phagocytosis by neutrophils or monocytes. The ingestion of
red cells, often coated with IgG or complement, is called erythrophagocytosis. Margination is the attachment of neutrophils
to the endothelial lining of the blood vessels.
What is the term for cell movement through blood vessels to a tissue site?

A. Diapedesis
B. Opsonization
C. Margination
D. Chemotaxis

D. Basophils

D. Basophil granules contain histamine, a potent vasodilator and smooth muscle contractor, that is responsible for the
systemic effects seen in immediate hypersensitivity reactions (type I), which are also termed anaphylaxis. Degranulation
occurs when basophils are coated with an IgE type of antibody that recognizes a specific allergen, such as bee venom,
certain plant pollens, or latex. The resulting anaphylactic shock can be life threatening.
Vasodilation and bronchoconstriction are the result of degranulation by which of the following blood cells?

A. Eosinophils
B. Monocytes
C. Neutrophils
D. Basophils
B. Monoclonal antibody reactions to surface and cytoplasmic antigens

B. Morphologic criteria such as cell size, nuclear shape, and chromatin pattern or cytoplasmic granularity cannot be used
to identify lymphocyte subtypes. Monoclonal antibodies (CD surface markers) to specific surface and cytoplasmic
antigens can distinguish lymphocyte subpopulations and identify the development stage. For example, blood lymphocytes
that are B cells express CD 19 and CD20 markers, T cells express CD2 and CDS (and either CD4 or CDS markers), and
NK cells express CD56. Natural killer cells often exhibit large granular lymphocyte morphology (LGLs).
On what basis can B and T lymphocytes be distinguished?

A. Differences in nuclear shape

B. Monoclonal antibody reactions to surface and cytoplasmic antigens
C. Cytoplasmic granularity and overall cell size
D. Chromatin pattern in the nucleus
B. Plasma cells

B. Plasma cells are the mature end stage of the B lymphocyte, producing immunoglobulins (antibodies) in response to
activation by a specific antigen (humoral immunity). The antibody produced by a single plasma cell is of one
immunoglobulin type. Natural killer (NK) cells recognize and kill tumor cells or cells infected with virus through direct
contact. Virocytes are reactive lymphocytes, and thymocytes are immature T cells. T lymphocytes provide cellular (cell
mediated) immunity.
Cells that produce immunoglobulins in response to antigenic stimulation are designated

A. Natural killer cells

B. Plasma cells
C. Virocytes
D. Thymocytes
A. Suppress allergic reactions caused by basophils

A. A function of the eosinophil is to modify the severe allergic reactions caused by degranulation of the basophil.
Neutrophils have receptors for the opsonins IgG and complement and are the most important cell in the initial defense
against acute bacterial infection. Neutrophils are nonspecific phagocytes, ingesting bacteria, fungi, dead cells, etc., and
they contain hydrolytic enzymes, including muramidase (lysozyme) and alkaline phosphatase. Neutrophils die in the
performance of their function and are removed by macrophages.
Which of the following statements about neutrophils is false?

A. Suppress allergic reactions caused by basophils

B. Have surface receptors for IgG and complement components
C. Contain alkaline phosphatase and muramidase
D. Act in nonspecific phagocytosis and are destined to die
C. Irregular, indented nuclear shape

C. The nucleus in both monocytes and reactive lymphocytes can be irregular in shape, with indentations, although a
monocyte nucleus often has folds and lobulations. Reactive lymphocytes characteristically have an increased amount of
dark blue cytoplasm, whereas monocyte cytoplasm is usually a blue-gray color. Lymphocytes lack the many fine granules
that give monocytes a typical "ground glass" appearance of the cytoplasm, but monocytes can occasionally have larger
granules. Sharp indentation of the cytoplasm by adjacent red cells and an increased number of large granules are
features of reactive lymphocytes. Vacuoles, although more commonly present in monocytes, can also be seen in reactive
lymphocytes.
Which of the following characteristics would be least likely to distinguish reactive lymphocytes from monocytes?

A. Sharp indentation of the cytoplasmic margin by adjacent red blood cells

B. Presence of large azurophilic granules
C. Irregular, indented nuclear shape
D. Abundant, deeply basophilic
cytoplasm
B. Indentation of nucleus

B. Indentation of the nucleus (kidney shape) is the feature that characterizes the metamyelocyte stage. Specific granules
begin forming in the myelocyte and persist through later stages. Cytoplasmic color is not a reliable feature, because it is
variable and may not differ significantly from the myelocyte or band stage. Nucleoli are absent in metamyelocytes and
may not be visible in myelocytes (they may be indistinct).
Which of the following can differentiate metamyelocytes from other stages of granulocyte maturation?

A. Presence of specific granules

B. Indentation of nucleus
C. Absence of nucleoli
D. Color of cytoplasm
A. 1 to 4 years

A. Young children have the highest peripheral lymphocyte concentrations, ranging from 4.0 to 10.5 X 109 cells/L at 1 year
of age and declining to 2.0-8.0 X 109 cells/L by 4 years of age. Lymphocyte counts decrease with age because of a
decrease in lymphocyte stimulation and processing of antigens, ranging from 1.0 to 4.0 X 109 cells/L in adults. In addition
to the difference in lymphocyte number in children, the normal morphology of children's lymphocytes differs from that of
adults. Patient age should be considered when deciding between normal and abnormal lymphocytes.
Lymphocyte concentrations in the peripheral blood are greatest during what age interval?

A. 1 to 4 years
B. 4 to 15 years
C. 16 to 40 years
D. 40 to 70 years
A. SIgM, a surface membrane
immunoglobulin

A. Early B cell precursors would be expected to express TdT, CD 10, and CD34. TdT, the enzyme marker for terminal
deoxynucleotidyl transferase, and the stem cell marker CD34 are present on the earliest B or T lymphoid cells. Surface
immunoglobulin (SIgM) can only be detected on B cells at later stages of development. TdT can be used to differentiate
the leukemic cells of acute lymphoid leukemia from acute myeloid leukemia. CALLA (CD 10 or common ALL antigen) is a
marker found in precursor types of B cell ALL.
Which of the following is the least likely to be expressed by early B cell precursors?

A. SIgM, a surface membrane

immunoglobulin
B. CD34, a hematopoietic stem cell marker
C. TdT (terminal deoxynucleotidyl transferase), a nuclear enzyme
D. CDlO(CALLA), a surface antigen
C. Their quantity of lysosomes and acid hydrolases decreases during maturation.

C. Acid hydrolases and the number of lysosomes increase as the blood monocyte matures into a tissue macrophage.
Macrophages are widely dispersed in body tissues and organs of the reticuloendothelial (RE) system (also known as the
mononuclear phagocyte system). Macrophages have receptors for IgG and complement,and they serve as phagocytes by
ingesting debris and dead cells (usually neutrophils) at sites of inflammation. Macrophages act in the immune response as
antigen-presenting cells by ingesting and exposing antigens for recognition by lymphocytes. Monocytes/macrophages
secrete complement components and cytokines, including colony stimulating factors and interleukins.
Which of the following statements about macrophages is incorrect?

A. They are mature tissue forms of blood monocytes.

B. They serve as antigen-presenting cells to the immune system.
C. Their quantity of lysosomes and acid hydrolases decreases during maturation.
D. They remove damaged or dying cells and cellular debris.
B. Spleen and lymph nodes

B. Antigen-independent lymphopoiesis occurs in primary lymphoid tissue located in the thymus and bone marrow. The
formation of immunocompetent T and B cells from the lymphoid progenitor cell is influenced by environment (thymus,
marrow) and several interleukins. Antigen-dependent lymphopoiesis occurs in secondary lymphoid tissue (spleen, lymph
nodes, Peyer's patches) and begins with antigenic stimulation of immunocompetent T and B cells. Lymphocytes are the
only white cells that recirculate (i.e., return to the blood from the tissues).
Antigen-dependent lymphopoiesis occurs in secondary lymphoid tissue located in the

A. Liver and kidney

B. Spleen and lymph nodes
C. Lungs and Peyer's patches
D. Thymus and bone marrow
D. Myeloperoxidase

D. Myeloperoxidase is an enzyme present in the primary granules, regardless of the phagocytic activity of the cell. The
products produced during the respiratory burst, many of them short lived, are generated in response to chemotactic
activation and ingestion of microbes. Generation of oxygen metabolites is necessary for microbial killing.
Which of the following is not produced by neutrophils during the respiratory burst?

A. Hydroxyl radicals (OH~)

B. Hydrogen peroxide (H2O2)
C. Superoxide anion (O^~)
D. Myeloperoxidase

C. B lymphocytes

C. The Epstein-BaiT vims (EBV) attaches to receptors on B lymphocytes, and the virus is incorporated into the cell. The
infection generates an intense immune response of T cells directed against infected B cells. It is the activated T
lymphocytes that comprise the majority of reactive lymphocytes seen in the blood of patients with infectious
mononucleosis. Other B cells produce nonspecific polyclonal (heterophile) antibody in response to the EBV infection.
In patients with infectious mononucleosis, which blood cells are infected by the causative agent?

A. Monocytes
B. T lymphocytes
C. B lymphocytes
D. Histiocytes
C. Hairy cells contain tartrate-resistant acid phosphatase.

C. The malignant cells of hairy cell leukemia (HCL) stain positive with acid phosphatase in the presence of tartaric acid;
that is, hairy cells contain tartrate-resistant acid phosphatase (TRAP). Normal cells stain acid phosphatase positive, but
staining is inhibited by the addition of tartrate. HCL is a chronic disorder, mainly confined to the elderly. The spleen usually
shows marked enlargement, but enlarged lymph nodes are very uncommon. Hairy cells are malignant B cells, and
pancytopenia is usual at presentation.
Which of the following statements about hairy cell leukemia is true?

A. It is an acute disease, primarily affecting young adults.

B. Splenomegaly is an unusual finding.
C. Hairy cells contain tartrate-resistant acid phosphatase.
D. Hairy cells are abnormal T lymphocytes.
A. Burkitt lymphoma

A. The lymphoid cells of B cell acute lymphoblastic leukemia (FAB type L3) are morphologically identical to the malignant
B cells of Burkitt lymphoma (large cells with basophilic cytoplasm and cytoplasmic lipid vacuoles). Although the site of
origin is the bone marrow in B cell ALL and the tissues in Burkitt lymphoma, the World Health Organization (WHO)
classifies them as the same disease entity with different clinical presentations (Burkitt leukemia/lymphoma). Both chronic
lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are malignant proliferations of small, mature
lymphocytes, and diagnosis is based on the predominant site of involvement. Mycosis fungoides and Sezary syndrome
are different stages of a cutaneous T cell lymphoma in which the skin is the early site of involvement, with subsequent
progression to the bone marrow and blood.
Based on the WHO classification system, B cell ALL (FAB type L3) and represent different clinical presentations of the
same disease entity.

A. Burkitt lymphoma
B. Hodgkin lymphoma
C. Mycosis fungoides
D. Small lymphocytic lymphoma
D. Leukoerythroblastic reaction

D. A leukoerythroblastic blood profile, which refers to the presence of both immature neutrophils and nucleated red cells,
is most commonly associated with conditions involving bone maiTOw infiltration by malignant cells (leukemia, cancer) or
replacement by fibrotic tissue. A neutrophilic left shift is defined as the presence of increased numbers of immature
neutrophils in the blood without nucleated red cells. A regenerative left shift and a neutrophilic leukemoid reaction are
characterized by varying degrees of leukocytosis and a neutrophilic left shift, most often found in response to infection. In
contrast, a degenerative left shift refers to leukopenia and a left shift that may occur if marrow pools are depleted in an
overwhelming infection (use exceeds the bone marrow's capacity to replace).
The presence of both immature neutrophils and nucleated erythrocytes in the peripheral blood is most accurately called a

A. Neutrophilic left shift

B. Regenerative left shift
C. Neutrophilic leukemoid reaction
D. Leukoerythroblastic reaction
A. Pelger-Huet

A. "True" Pelger-Huet anomaly is a benign autosomal dominant trait characterized by hyposegmentation of the
granulocytes, coarse nuclear chromatin, and normal cytoplasmic granulation. The cells have no functional defect. It is of
practical importance to recognize this anomaly so that it is not confused with a shift to the left due to infection. Acquired or
"pseudo" Pelger-Huet is commonly associated with myeloproliferative disorders, myelodysplastic syndromes, or drug
therapy. Pelgeroid cells are hyposegmented and the cytoplasm is frequently hypogranular.
In which anomaly is a failure of granulocytes to divide beyond the band or twolobed stage observed?

A. Pelger-Huet
B. May-Hegglin
C. Alder-Reilly
D. Chediak-Higashi
A. Cushing syndrome

A. Eosinophils are decreased in Gushing syndrome, in which the adrenal glands secrete large
amounts of adrenocorticosteroids. Eosinophils are increased in allergic disorders, various skin diseases, and certain types
of parasitic infections (especially those due to intestinal and tissuedwelling worms). Eosinophilia is also seen in chronic
myelogenous leukemia and Hodgkin lymphoma.
In which of the following are eosinophils not increased?

A. Cushing syndrome
B. Allergic disorders
C. Skin disorders
D. Parasitic infection
D. Oxidative respiratory burst

D. Chronic granulomatous disease (CGD) is a hereditary disorder in which neutrophils are incapable of killing most
ingested microbes. The disease is usually fatal because of defective generation of oxidative metabolism products, such as
superoxide anions and hydrogen peroxide, which are essential for killing. Chemotaxis, lysosomes, phagocytosis, and
neutrophil morphology are normal. Several variants of CGD have been described, with specific enzyme defects and
different modes of inheritance. The more common type of CGD has a sex-linked inheritance pattern.
Which of the following represents the principal defect in chronic granulomatous disease (CGD)?

A. Chemotactic migration
B. Phagocytosis
C. Lysosomal formation and function
D. Oxidative respiratory burst
B. A folate antagonist (e.g., methotrexate)

B. A drug-induced megaloblastic blood profile with macrocytic ovalocytes and hypersegmented neutrophils is shown in
Color Plate 11. This is a common finding in patients receiving antifolate chemotherapeutic drugs such as methotrexate.
Recombinant erythropoietin is associated with a reticulocyte response and used to treat a variety of conditions, such as
renal disease, anemia of chronic disease, or anemia caused by chemotherapy. Chloramphenicol is an antibiotic with a
known association for aplasia due to marrow suppression.
The blood shown in Color Plate 11 is from a leukemia patient following treatment. These findings are most suggestive of
therapy with

A. Corticosteroids (e.g., prednisone)

B. A folate antagonist (e.g., methotrexate)
C. Recombinant erythropoietin
D. Chloramphenicol
C. Essential thrombocythemia

C. Primary or essential thrombocythemia (ET) is a chronic myeloproliferative disorder in which the main cell type affected
is the platelet. An extremely high number of platelets are produced, but abnormal platelet function leads to both bleeding
and clotting problems. The bone marrow shows megakaryocytic hyperplasia. The hemoglobin value and platelet count are
increased in polycythemia vera, and CML is characterized by a high WBC count. Malignant thrombocythemia must be
differentiated from a reactive thrombocytosis seen in patients with infection or following surgery. In reactive causes, the
platelet count is rarely over 1 million X 109/L, platelet function is normal, and thrombocytosis is transient.
A patient with normal hemoglobin and WBC count values, a persistently elevated platelet count (over 1000 X 109/L),
increased marrow megakaryocytes, and a history of frequent bleeding and clotting episodes most likely has

A. Polycythemia vera
B. Chronic myelofibrosis
C. Essential thrombocythemia
D. Chronic myelogenous leukemia
B. Idiopathic myelofibrosis

B. The bone marrow is progressively replaced by fibrotic tissue in myelofibrosis, a chronic myeloproliferative disorder.
Attempts to aspirate bone marrow usually result in a "dry tap." A biopsy stain demonstrates increased fibrosis (fibroblasts
are thought to be stimulated by megakaryocytes). The presence of teardropshaped red blood cells is an important feature
of myelofibrosis. In addition, abnormal platelets, a leukoerythroblastic blood profile and myeloid metaplasia in the spleen
and liver are often associated with this disease. A high LAP score (reference range 13-160) and increased RBC mass are
found in polycythemia vera, but the LAP score is low in chronic myelogenous leukemia.
An adult patient with massive
splenomegaly has mild anemia, a slightly elevated WBC count, and an LAP score of 170. The blood smear shows
teardrop erythrocytes and leukoerythroblastosis. These findings are most consistent with

A. Chronic myelogenous leukemia

B. Idiopathic myelofibrosis
C. Primary polycythemia
D. Primary thrombocythemia
B. Bordetella pertussis (whooping cough)

B. A striking lymphocytosis may be seen in children with pertussis, but normal lymphocytes, rather than reactive
lymphocytes, are present. A relative and/or absolute lymphocytosis with reactive lymphocytes in various stages of
activation, as seen in Color Plate 121, is characteristic of infection caused by Epstein-Barr virus (EBV), cytomegalovirus
(CMV), and toxoplasmosis. A positive heterophile antibody test can help distinguish infectious mononucleosis caused by
EBV from conditions with a similar blood picture. Epstein-Barr virus is also linked to Burkitt and Hodgkin lymphomas.
Which of the following infections does not reveal a blood picture as seen in Color Plate 12?

A. Epstein-Barr virus (EBV)

B. Bordetella pertussis (whooping cough)
C. Cytomegalovirus (CMV)
D. Toxoplasma gondii (toxoplasmosis)
A. B cell

A. B cell chronic lymphocytic leukemia (CLL) is by far the most common type found in the United States. Immune
dysfunction because of hypogammaglobulinemia occurs in later stages of the disease, as does thrombocytopenia.
Development of warm autoimmune hemolytic anemia is a frequent occurrence in patients with CLL. Treatment for B cell
CLL is conservative and aimed at controlling symptoms. T cell CLL is a rare and is a more aggressive disease.
The most common type of chronic lymphocytic leukemia (CLL) in the United States involves the

A. B cell
B. NK cell
C. T cell
D. Plasma cell
D. Increased IgM and blood hyperviscosity

D. Waldenstrom macroglobulinemia is caused by a proliferation of transitional B lymphocytes (lymphoplasmacytic or

plasmacytoid lymphs) that secrete high amounts of monoclonal IgM. Because IgM is a macroglobulin, blood
hyperviscosity is the cause of many of the symptoms found in this disease (bleeding and visual impairment).
Plasmapheresis can reduce the IgM protein concentration. Hepatosplenomegaly is common in Waldenstrom disease
(rather than bone lesions).
Which of the following are characteristic findings in Waldenstrom disease?

A. Increased IgA and hepatosplenomegaly

B. Increased IgE and renal failure
C. Increased IgG and hypercalcemia
D. Increased IgM and blood hyperviscosity
C. Human immunodeficiency virus (HIV)

C. The elevated WBC count and toxic neutrophils seen in Color Plate 13 indicate an extreme response to severe infection
(bacterial septicemia, fungal) or treatment with recombinant myeloid growth factors. GM-CSF and GCSF are used to
increase cells for peripheral stem cell transplant and reduce infection in patients after high-dose chemotherapy or during
transplant. A leukemoid reaction is one that mimics the type of blood picture seen in leukemia. It is associated with
extremely high leukocyte counts (often greater than 50 X 109 cells/L) and is usually found in severe infection. The most
common type of leukemoid reaction is neutrophilic, but lymphocytic leukemoid reactions also occur. HIV infection is
associated with leukopenia and lymphocytopenia.
Which of the following would not cause a total WBC count of 62.2 X 109/L (62.2 X 103/uL) and the blood findings seen in
Color Plate 13?

A. Treatment with myeloid growth factors

B. Gram-negative septicemia
C. Human immunodeficiency virus (HIV)
D. Systemic fungal infection
B. Chronic lymphocytic leukemia

B. The blood shown in Color Plate 14 is from an elderly patient with chronic lymphocytic leukemia (CLL), which is
characterized by an absolute lymphocytosis and a predominance of small, mature lymphocytes with hyperclumped
nuclear chromatin. Elevated leukocyte counts are usual, as are fragile, smudged lymphocytes. Acute lymphoblastic
leukemia (ALL) typically occurs in children and is characterized by immature lymphoid cells. Plasmacytoid lymphocytes
and red cell rouleaux may be found in the blood of individuals with Waldenstrom disease. Viral infections are associated
with a lymphocytosis and the presence of reactive lymphocytes that are heterogeneous in morphology. Reactive
lymphocytes exhibit a variety of forms with regard to size and cytoplasmic staining intensity as compared to the
homogeneous cell populations present in malignant disorders such as CLL and ALL.
The peripheral blood shown in Color Plate 14 is from a 69-year-old female. Her WBC count was 83.0 X 109 cells/L (83.0
X 103/(xL) and her platelet count was normal. Based on the cell morphology and this information, what is the most likely
diagnosis?

A. Acute lymphoblastic leukemia

B. Chronic lymphocytic leukemia
C. Waldenstrom macroglobulinemia
D. Viral infection
D. Chronic lymphocytic leukemia (CLL)

D. Progression to acute leukemia is a very unlikely event for patients with chronic lymphocytic leukemia, even though
there is no cure. Patients with chronic myelogenous leukemia typically progress to "blast crisis," most often of myeloid
type, unless treated with imatinib mesylate (Gleevec®) in the chronic phase. Refractory anemia with excess blasts
(RAEB) is the most likely type of myelodysplastic syndrome to develop acute myelogenous leukemia. Refractory anemia
with ringed sideroblasts (RARS) is "preleukemic" but fairly stable.
In which of the following is progression to acute leukemia least likely?

A. Chronic myelogenous leukemia (CML)

B. Refractory anemia with excess blasts (RAEB)
C. Refractory anemia with ringed sideroblasts (RARS)
D. Chronic lymphocytic leukemia (CLL)
A. "Wrinkled" cytoplasm due to an accumulation of glucocerebroside

A. Gaucher disease is a lipid storage disorder in which there is an accumulation of glucocerebroside in the macrophages
because of a genetic lack of glucocerebrosidase, an enzyme required for normal lipid metabolism. Gaucher cells are
found in the liver, spleen, and bone marrow. Niemann-Pick disease is caused by a deficiency of sphingomyelinase in
which "foamy" macrophages, called Niemann-Pick cells, are filled with sphingomyelin. Normal acrophages may contain
iron and other cellular debris.
A Gaucher cell is best described as a macrophage with

A. "Wrinkled" cytoplasm due to an accumulation of glucocerebroside

B. "Foamy" cytoplasm filled with
unmetabolized sphingomyelin
C. Pronounced vacuolization and deposits of cholesterol
D. Abundant cytoplasm containing storage iron and cellular remnants
D. Presence of giant binucleated Reed Sternberg
cells with prominent nucleoli

D. The presence of Reed-Sternberg cells is the diagnostic feature of Hodgkin disease (lymphoma). The Reed Sternberg
giant cell is usually binucleated, and each lobe has a prominent nucleolus. Studies suggest that this neoplastic cell is of B
cell lineage. It is not found in the blood but only in the tissues. Circulating T cells with a convoluted nucleus describe the
Sezary cells seen in Sezary syndrome, the leukemic phase of mycosis fungoides. A monoclonal population of large
lymphoid cells or immature B cells with nuclear clefts is most descriptive of lymphoma cells, present in certain types of
peripheralized non-Hodgkin lymphoma, that have spread from the tissues to the bone marrow and blood.
Which of the following suggests a diagnosis of Hodgkin disease rather than other lymphoproliferative disorders?

A. Presence of a monoclonal population of large lymphoid cells

B. Predominance of immature B cells with irregular nuclear clefts
C. Circulating T cells with a convoluted, cerebriform nucleus
D. Presence of giant binucleated Reed Sternberg
cells with prominent nucleoli
B. Increased albumin level

B. The overall reaction of the body to tissue injury or invasion by an infectious agent is known as inflammation. This
response brings leukocytes to the site of infection or tissue damage and is associated with activation of inflammatory
mediators, including cytokines (IL-1), molecules released by cells (histamine), and byproducts of plasma enzyme systems
(complement, kinins, fibrin). The plasma concentration of positive acute-phase reactants (APRs), such
In a patient with fever of unknown origin, which of the following findings is not consistent with an inflammatory process?

A. Increased C-reactive protein

B. Increased albumin level
C. Increased fibrinogen level
D. Increased erythrocyte sedimentation rate
C. Acute promyelocytic leukemia (FAB type M3)

C. The abnormal cells found in acute promyelocytic leukemia (FAB type M3) contain large numbers of azurophilic
granules. These granules contain procoagulants that on release hyperactivate coagulation, resulting in disseminated
intravascular coagulation. Although other acute leukemias may trigger DIG, M3 is the one most frequently associated with
this life-threatening bleeding complication. If DIG is resolved, many patients with acute promyelocytic leukemia respond
favorably to therapy with retinoic acid, which causes maturation of the malignant promyelocytes. The presence of t(15;17)
has diagnostic and prognostic significance, and acute promyelocytic leukemia is classified with "acute myeloid leukemias
with recurrent cytogenetic translocations" by the World Health Organization (WHO). Acute myeloblastic leukemia with
t(8;21) is also included in this WHO category (con-elates with FAB type M2).
The presence of the chromosomal abnormality t(15;17) and a high incidence
of disseminated intravascular coagulation (DIC) is diagnostic of

A. Acute myeloblastic leukemia without maturation (FAB type Ml)

B. Acute myeloblastic leukemia with maturation (FAB type M2)
C. Acute promyelocytic leukemia (FAB type M3)
D. Acute myelomonocytic leukemia (FAB type M4)
D. Lymphadenopathy

D. Although a hallmark of acute lymphoblastic leukemias (ALL), lymphadenopathy is not associated with acute
myelogenous leukemias. ALL is also more likely to have central nervous system involvement, and the CNS is a potential
site of relapse. Hepatomegaly and splenomegaly are associated with both types of acute leukemia, as well as with the
presence of anemia, neutropenia, and thrombocytopenia. Common presenting symptoms are fatigue, infection, or
bleeding. If untreated, both acute myelogenous and lymphoblastic leukemias have a rapidly fatal course.
Which of the following is not commonly found in acute myelogenous leukemias?

A. Neutropenia
B. Thrombocytopenia
C. Hepatosplenomegaly
D. Lymphadenopathy
B. CD10,CD19

B. The blast cells shown in Color Plate 15 are from a child with CALLA positive, precursor B acute lymphoblastic
leukemia. The malignant cells would be expected to express CD 10, the common ALL antigen marker; the B cell lineage
marker CD 19; and TdT (terminal deoxynucleotidyl transferase), a marker on early lymphoid cells. Precursor T acute
lymphoblastic leukemia would express TdT and the T cell markers CD2 and CD7. CD 13 and CD33 are myeloid markers,
and CD14 is a marker for monocytic cells.
The child whose blast cells are shown in Color Plate 15 has acute lymphoblastic leukemia that is precursor B cell type and
CALLA positive. Analysis by flow cytometry would likely show cells that immunophenotype for

A. CD2,CD7
B. CD10,CD19
C. CD13,CD33
D. CD14,CD34
A. Acute leukemia

A. The "packed" bone marrow with predominantly immature blast cells and few normal precursor cells, as seen in Color
Plate 16, is most indicative of a patient with acute leukemia. Although chronic leukemias usually have a hypercellular
marrow, the malignant cells are more mature or differentiated (i.e., able to mature beyond the blast stage).
Myelodysplastic syndromes are associated with a hypercellular bone marrow, but the marrow blast percent is less than
20% (using WHO criteria). Aplastic anemia is characterized by a hypocellular bone marrow with few cells.
The patient whose bone marrow is shown in Color Plate 16 most likely has a(n)

A. Acute leukemia
B. Chronic leukemia
C. Myelodysplastic syndrome
D. Aplastic anemia
C. IgG light chains

C. The secretion of large amounts of monoclonal IgG or other immunoglobulin light chains by a malignant clone of plasma
cells produces a characteristic M spike on serum and urine protein electrophoresis. In some cases, only the light chains
are produced in excess. Because the light chains are easily cleared by the kidneys, they may appear only in the urine
(Bence-Jones proteinuria). Renal impairment in multiple myeloma is associated with the toxic effects of filtered light
chains. High levels of serum beta microglobulin correlate with the myeloma tumor burden. Cryoglobulins are proteins that
precipitate in the cold and may be seen in multiple myeloma and Waldenstrom macroglobulinemia.
Multiple myeloma is characterized by the presence in urine of large amounts of

A. Cryoglobulins
B. IgG heavy chains
C. IgG light chains
D. Beta microglobulins
C. Multiple myeloma

C. Multiple myeloma is a malignant lymphoI proliferative disorder characterized by a clonal proliferation of plasma cells
and multiple bone tumors. Myeloproliferative disorders are characterized by a proliferation of bone marrow cells
(granulocytic, monocytic, erythrocytic, megakaryocytic), with usually one cell type primarily affected. For example, the
main cell type affected in polycythemia vera is the erythrocyte, and the platelet is mainly affected in essential
thrombocythemia. Transformation among the myeloproliferative disorders is frequent.
Which of the following is not classified as
a myeloproliferative disorder?

A. Polycythemia vera
B. Essential thrombocythemia
C. Multiple myeloma
D. Chronic myelogenous leukemia

B. BCR/ABL

B. The Philadelphia chromosome, t(9;22), is detected in almost all cases of CML (depends on detection method) and
results in a mutated BCR/ABL fusion gene. The resulting fusion protein causes increased tyrosine kinase activity, which
promotes cell proliferation. Imatinib mesylate (Gleevec®) is a therapeutic agent that targets the molecular defect by
blocking tyrosine kinase activity and is now a first-line drug used in the chronic phase of CML.
Which of the following gene mutations correlates with the t(9;22) that is present in Philadelphia chromosome positive
chronic myelogenous leukemia?

A. MYC/IGH
B. BCR/ABL
C. PML/RARA
D. JAK2
B. Diagnosis is based on cellular morphology and cytochemistry.

B. The French-American-British (FAB) classification of acute leukemias, myeloproliferative disorders, and myelodysplastic
diseases was originally based on cellular morphology and cytochemistry (immunophenotyping was later added). Using
FAB criteria, acute leukemia was defined as greater than 30% bone marrow blasts. The diagnostic criteria used by the
World Health Organization (WHO) includes morphologic, cytochemical, immunologic, cytogenetic, and molecular features,
as well as clinical findings, to better characterize all hematologic malignancies (myeloid and lymphoid) and predict disease
course. The WHO classification defines acute leukemia as the presence of 20% or more bone marrow blasts and includes
diagnostic categories with recurrent cytogenetic abnormalities. According to the WHO classification, lymphoid disorders
are grouped into B cell, T/NK cell, and Hodgkin lymphoma. Further division of the B and T cell neoplasms considers site
of involvement and precursor cell versus mature cell conditions.
Which of the following statements does not correctly describe the WHO (World Health Organization) classification of
hematopoietic neoplasms?

A. Acute leukemia is defined as the presence of at least 20% bone marrow blasts.
B. Diagnosis is based on cellular morphology and cytochemistry.
C. It groups lymphoid disorders into
B cell, T/NK cell, and Hodgkin
lymphoma.
D. Diagnostic criteria include morphologic, cytochemical, immunologic, cytogenetic, and molecular features.
A. An extreme leukocytosis with increased neutrophilic bands, metamyelocytes, and myelocytes

A. The blood profile of both chronic myelogenous leukemia (CML) and a neutrophilic leukemoid reaction is characterized
by extremely high leukocyte counts with immature neutrophils. Splenomegaly is a manifestation of the malignant disease
process and associated with CML rather than a leukemoid reaction. The presence of toxic granules and Dohle bodies
would be typical of a leukemoid reaction caused by a severe bacterial infection. The LAP score is low in CML and high in
a neutrophilic leukemoid reaction.
Which of the following would be least helpful in distinguishing chronic myelogenous leukemia (CML) from a neutrophilic
leukemoid reaction?

A. An extreme leukocytosis with increased neutrophilic bands, metamyelocytes, and myelocytes

B. Leukocyte alkaline phosphatase score
C. Presence of marked splenomegaly
D. Neutrophils with Dohle bodies and toxic granulation
C. Stains positive with myeloperoxidase (MPO)

C. In Color Plate 17, the malignant blast cell contains an Auer rod, composed of fused primary granules, which stains
positive with both myeloperoxidase and Sudan black B. Auer rods are not seen in lymphoblasts, and their presence can
be diagnostic of acute myelogenous leukemia, such as acute myeloblastic leukemia (FAB types Ml and M2) or acute
myelomonocytic leukemia (FAB type M4). Multiple Auer rods may be seen in acute promyelocytic leukemia (FAB type
M3). Auer rods stain negatively with LAP, which detects the enzyme alkaline phosphatase in neutrophil granules.
The cytoplasmic inclusion present in the cell shown in Color Plate 17

A. Excludes a diagnosis of acute myelogenous leukemia

B. Stains positive with leukocyte alkaline phosphatase (LAP)
C. Stains positive with myeloperoxidase (MPO)
D. Identifies the cell as a malignant lymphoblast
D. Elevated leukocyte count

D. At presentation, patients with chronic leukemia (e.g., CLL or CML) consistently have elevated leukocyte counts,
whereas individuals with acute leukemia may present with low, normal, or high leukocyte counts. The hallmark findings of
anemia, thrombocytopenia, and neutropenia are often found in patients with acute leukemia at the time of diagnosis and
are due to replacement of normal marrow hematopoietic cells by blasts. Patients with chronic leukemia may have few
symptoms at onset, with anemia and thrombocytopenia developing during progression of the disease.
Which of the following is a typical finding in chronic leukemias at onset?

A. Symptoms of infection and bleeding

B. Significant thrombocytopenia
C. Severe anemia
D. Elevated leukocyte count
D. Chronic myelogenous leukemia

D. Leukocyte alkaline phosphatase (LAP) scores are usually low in patients with chronic myelogenous leukemia (CML).
The LAP reflects alkaline phosphatase activity in neutrophils, and the score is usually elevated in conditions where
neutrophils are activated and/or increased in number, such as late pregnancy, bacterial infection, and polycythemia vera.
The primary use of the LAP is to distinguish between the malignant cells of CML and a severe bacterial infection
(leukemoid reaction). It may also be used to distinguish between CML and other chronic myeloproliferative disorders such
as polycythemia vera. The LAP may be called NAP (neutrophil alkaline phosphatase) stain.
In what condition would an LAP score of 10 most likely be found?

A. Bacterial septicemia
B. Late pregnancy
C. Polycythemia vera
D. Chronic myelogenous leukemia
C. Infectious hepatitis

C. Acute viral hepatitis is associated with lymphocytosis. The major causes of neutrophilia are bacterial infection,
neoplastic tumors, and inflammatory responses to tissue injury. "Toxic" neutrophils may be present (toxic granulation,
Dohle bodies, vacuolization). Infection with organisms other than bacteria (fungi, some parasites, certain viruses) may
also cause neutrophilia.
Which of the following is not associated with neutrophilia?

A. Staphylococcal pneumonia
B. Crushing injury
C. Infectious hepatitis
D. Neoplasms (tumors)
D. Infectious mononucleosis

D. Monocytes must be distinguished from reactive lymphocytes, which are the characteristic feature of infectious
mononucleosis. Monocytosis occurring in the recovery stage of acute infections is considered a favorable sign. An
increase in monocytes is associated with collagen disorders (e.g., rheumatoid arthritis), tuberculosis, and malignant
conditions such as myelodysplastic syndromes and monocytic leukemias.
In which of the following would an absolute monocytosis not be seen?

A. Tuberculosis
B. Recovery stage of acute bacterial infection
C. Collagen disorders
D. Infectious mononucleosis
B. Acute lymphoblastic leukemia (FAB type L1)

B. The periodic acid-Schiff (PAS) stain can be used to detect intracellular glycogen deposits in the lymphoblasts of acute
lymphoblastic leukemia (ALL), in which coarse clumps of PAS positive material may be observed. Myeloblasts and
monoblasts usually show a faint staining reaction. The immunophenotype has a much greater diagnostic value for ALL
than the cytochemical stain results. The PAS may also be used to distinguish the malignant erythroid precursors of acute
erythroleukemia, which show strong PAS positivity, from normal erythrocytic cells that stain negative.
Coarse PAS positivity may be found in the leukemic cells of

A. Acute myeloblastic leukemia (FAB type M1)

B. Acute lymphoblastic leukemia (FAB type L1)
C. Acute myelomonocytic leukemia (FAB type M4)
D. Acute monocytic leukemia (FAB type M5)
D. Hypocellular bone marrow with 25% blasts

D. Myelodysplastic syndromes (MDSs) are characterized by a hypercellular bone marrow and up to 20% marrow blasts
that distinguish MDS from acute leukemia (using WHO criteria). The blood and bone marrow blast percentages differ, and
the risk of transformation to acute leukemia varies with the types of MDSs.
Which of the following is not among the diagnostic criteria used for classifying the myelodysplastic syndromes?

A. Unexplained anemia refractory to treatment

B. Hypogranular and hyposegmented neutrophils
C. Abnormal platelet size and
granulation
D. Hypocellular bone marrow with 25% blasts
A. Granulocytic; monocytic

A. Naphthol AS-D chloroacetate esterase (specific) reacts strongly in granulocytic cells, and alpha-naphthyl acetate
esterase (nonspecific) stains positively in monocytic cells. The esterase stains are used to distinguish between subtypes
of acute myelogenous leukemia. The cells of acute myeloblastic leukemia (FAB types Ml and M2) will stain positive with
specific esterase and negative with nonspecific esterase. The cells of acute monocytic leukemia (FAB type M5) will stain
positive with nonspecific esterase and negative with specific esterase. The cells of acute myelomonocytic leukemia (FAB
type M4) will show positivity with both specific and nonspecific esterase. Stain results are correlated with cell morphology,
immunophenotype, and karyotype for diagnosis.
Naphthol AS-D chloroacetate esterase (specific) is usually positive in cells, and alphanaphthyl acetate esterase
(nonspecific) is useful for identifying blast cells of lineage

A. Granulocytic; monocytic
B. Monocytic; granulocytic
C. Granulocytic; lymphocytic
D. Monocytic; lymphocytic
A. May-Hegglin anomaly

A. May-Hegglin anomaly is an autosomal dominant disorder in which large blue cytoplasmic structures that resemble
Dohle bodies are found in the granulocytes and possibly the monocytes. Leukocytes are normal in function. Platelets are
decreased in number and abnormally large. About one-third of patients have mild to severe bleeding problems because of
abnormal platelet function.
The familial disorder featuring pseudoDohle bodies, thrombocytopenia, and
large platelets is called

A. May-Hegglin anomaly
B. Chediak-Higashi syndrome
C. Pelger-Huet anomaly
D. Alder-Reilly anomaly
D. Mucopolysaccharide metabolism

D. Alder-Reilly anomaly is a hereditary autosomal recessive disorder caused by a deficiency of enzymes involved in the
metabolism of mucopolysaccharides. Partially degraded mucopolysaccharides accumulate in various tissues, organs, and
the leukocytes that are characterized by the presence of large azurophilic granules resembling toxic granulation. The
inclusions do not affect leukocyte function and are referred to as Alder-Reilly bodies. The anomaly is often associated with
facial and skeletal abnormalities, such as those seen in Hunter syndrome and Hurler syndrome. Lysosomal fusion with
impaired degranulation is the defect in Chediak Higashi syndrome and is associated with early death due to abnormal
leukocyte function.
Alder-Reilly anomaly is an abnormality of

A. Lysosomal fusion
B. Nuclear maturation
C. Oxidative metabolism
D. Mucopolysaccharide metabolism
C. Serum and urine protein
electrophoresis

C. Serum and urine protein electrophoresis detects the presence of an M spike, the first essential step in establishing the
disorder as a monoclonal gammopathy such as multiple myeloma or Waldenstrom disease. This can be followed by
immunoelectrophoresis to determine the class of immunoglobulin or chain type. Immunologic markers, cytochemical
stains, and/or cytogenetics are used in conjunction with cell morphology to diagnose malignant conditions.
What is the initial laboratory technique for the diagnosis of monoclonal gammopathies?

A. Immunologic markers of marrow

biopsy cells
B. Cytochemical staining of marrow and
peripheral blood cells
C. Serum and urine protein
electrophoresis
D. Cytogenetic analysis of marrow cells
C. Stage IV has the best prognosis

C. The prognosis is poor for patients with stage IV Hodgkin disease, in which there is widespread disease including bone
marrow involvement. Stage I or II Hodgkin disease has a very good prognosis for cure. The clinical course and treatment
varies with the extent of disease and morphologic subtype (Rye classification). The peak incidence for Hodgkin lymphoma
occurs in young adults (late twenties). Men have a 50% higher incidence of the disease than women. The CRP level and
ESR are increased during active disease and can be used to monitor remission status.
Which of the following statements about Hodgkin disease is false?

A. Peak incidence occurs in young adults.

B. Staging determines extent of disease and treatment course.
C. Stage IV has the best prognosis.
D. Almost a 2:1 male predominance over females is characteristic.
C. Acute myelomonocytic leukemia

C. The acute leukemia indicated by these results is acute myelomonocytic leukemia (AMML), which has both granulocytic
and monocytic features. Note the monocytic characteristics of the blast cells in Color Plate 18«. CD 14 is a monocytic
marker and CDS 3 is a marker for primitive myeloid cells. The SBB shows positive staining in both granulocytic and
monocytic cells, the specific esterase stains positive in granulocytic cells, and the nonspecific esterase is positive in
monocytic cells.
The blast cells shown in Color Plate 18 are CD14 and CD33 positive, Sudan black B positive, specific esterase positive,
and nonspecific esterase positive. Which type of acute leukemia is most consistent with the immunophenotyping and
cytochemical staining results?

A. Acute lymphoblastic leukemia, T cell type

B. Acute erythroleukemia
C. Acute myelomonocytic leukemia
D. Acute monocytic leukemia
B. Acute lymphoblastic leukemia in children

B. Acute lymphoblastic leukemia (ALL) of children has the best prognosis. Other favorable factors include children
between ages 3 and 7, mild to moderate increases in the peripheral white blood count prior to treatment, and precursor B
ALL, CALLA positive type (rather than T cell ALL). Certain cytogenetic and molecular abnormalities are also associated
with a better prognosis. Acute leukemia in adults is less favorable because remissions are shorter and more difficult to
induce, especially in thos in over 70 years of age. Prognosis is poor in adults with ALL.
Which type of leukemia is associated with the best prognosis for a cure?

A. Chronic lymphocytic leukemia in the elderly

B. Acute lymphoblastic leukemia in children
C. Acute myelogenous leukemia in children
D. Chronic myelogenous leukemia in young adults
B. Lymph node biopsy

B. The test that would be the most beneficial for the diagnosis of Hodgkin lymphoma is a lymph node biopsy.
Lymphadenopathy is the major clinical presentation of Hodgkin disease, and early stages do not have bone marrow
involvement. A skin biopsy would be indicated for diagnosis of mycosis fungoides, a T cell lymphoma of the skin. A bone
marrow exam and spinal tap are important to the diagnosis of acute leukemias.
What is the key diagnostic test for Hodgkin lymphoma?

A. Bone marrow biopsy

B. Lymph node biopsy
C. Spinal tap
D. Skin biopsy
A. Chronic myelogenous leukemia

A. A hypercellular bone marrow and high M:E ratio are most characteristic of the excessive granulocyte production that
occurs in chronic myelogenous leukemia. Polycythemia vera typically has a hypercellular marrow with panhyperplasia and
a normal or low M:E ratio. Beta-thalassemia major is a severe hemolytic anemia in which RBC hyperplasia of the marrow
is pronounced and a low M:E ratio is usual. Aplastic anemia is associated with a hypocellular marrow with a reduction of
all cell lines and normal M:E ratio.
A bone marrow with 90% cellularity and myeloid:erythroid (M:E) ratio of 10:1 is most characteristic of

A. Chronic myelogenous leukemia

B. Primary polycythemia
C. Beta-thalassemia major
D. Aplastic anemia
B. Refractory anemia with ringed sideroblasts (RARS)

B. Refractory anemia with ringed sideroblasts (RARS) is a myelodysplastic syndrome (MDS) that may also be referred to
as primary or idiopathic sideroblastic anemia. The main findings that characterize this type of MDS include refractory
anemia with a heterogeneous population of red cells, a hypercellular bone marrow with <5% blasts, and the presence of
>15% ringed sideroblasts in the marrow (demonstrated with Paissian blue stain). RA and RARS are the least likely MDS
types to progress to acute myelogenous leukemia
A 60-year-old patient presents with extreme fatigue. Her blood and bone marrow findings are as follows:
severe anemia with a dual RBC population, 3% marrow blasts, and numerous ringed sideroblasts. This information is
most consistent with

A. Refractory anemia (RA)

B. Refractory anemia with ringed sideroblasts (RARS)
C. Refractory anemia with excess blasts (RAEB)
D. Chronic myelomonocytic leukemia (CMML)
C. Recent strenuous exercise

C. Recent strenuous exercise or other physical and emotional stimuli cause a transient increase in the leukocyte count.
This is due to a redistribution of the blood pools. Marrow injury to stem cells or marrow replacement by malignant cells
causes neutropenia of varying degrees. Neutropenia may be caused by immune mechanisms (antibodies) or an
overactive spleen that sequesters neutrophils. Chemotherapeutic drugs also suppress bone marrow production of
neutrophils
Which of the following is not a mechanism by which neutropenia may be produced?

A. Hypersplenism
B. Marrow injury or replacement
C. Recent strenuous exercise
D. Drug-induced antibodies
C. Increased erythropoietin leve

C. Primary polycythemia (vera) is a malignant myeloproliferative disorder characterized by autonomous marrow

production of erythrocytes in the presence of low erythropoietin levels. Usual findings include increased RBC mass with
elevated hemoglobin values and variable degrees of leukocytosis and thrombocytosis (pancytosis). Splenomegaly, a high
LAP score, thrombotic tendencies, and problems caused by blood viscosity are typical. Phlebotomy is done to reduce red
cell mass.
Which of the following is not a characteristic finding in polycythemia vera?

A. Blood pancytosis
B. Increased red cell mass
C. Increased erythropoietin level
D. Increased blood viscosity
D. Chronic myelogenous leukemia

D. Basophilia (and eosinophilia) is a typical finding in patients with chronic myelogenous leukemia (CML). A progressive
increase in basophil number suggests transformation of the disease to a more accelerated phase. Myeloproliferative
disorders such as CML, polycythemia vera, or AML are often associated with peripheral basophilia, which is not a feature
of lymphoproliferative disorders such as acute lymphoblastic leukemia, hairy cell leukemia, or plasma cell leukemia.
In what disorder is significant basophilia most commonly seen?

A. Hairy cell leukemia

B. Plasma cell leukemia
C. Acute lymphoblastic leukemia
D. Chronic myelogenous leukemia
C. Marrow erythroblasts and multinucleated red cells

C. More than 50% of the marrow cells are erythroid in acute erythroleukemia (FAB type M6). Giant erythroid precursors,
bizarre and multinucleated red cells, and increased myeloblasts are found in the marrow and may appear in the blood.
Acute erythroid leukemia is rare, and the disease typically evolves into acute myeloblastic leukemia (FAB types Ml or M2).
Acute erythroleukemia (FAB type M6) is characterized by increased

A. Promyelocytes and lysozyme activity

B. Marrow megakaryocytes and
thrombocytosis
C. Marrow erythroblasts and multinucleated red cells
D. Marrow monoblasts and immature monocytes
D. Normal sedimentation rate

D. Plasma cell myeloma is a clonal disease involving malignant end-stage B cells, in which overproduction of
immunoglobulin is a hallmark and the presence of red cell rouleaux is a characteristic finding on the blood smear, as
shown in Color Plate 20«. Excessive amounts of a monoclonal immunoglobulin result in the deposition of proteins on
circulating red cells that causes red cell "coining." The erythrocyte sedimentation rate is extremely elevated because of
spontaneous rouleaux formation. Multiple myeloma is characterized by bone pain and spontaneous bone fractures
caused by tumors of plasma cells. Bone destruction leads to elevated calcium levels, and renal impairment can result
from damage by excess light chains. Plasma cells progressively crowd out normal bone marrow precursors and may be
found in the blood circulation in advanced disease. Treatment with thalidomide has improved survival.
The blood findings present in Color Plate 20 are from a patient with complaints of fatigue and severe lower back pain.
Which of the following would not be typical of this disease?

A. Bone tumors of plasma cells

B. Hypercalcemia
C. Progressive renal impairment
D. Normal sedimentation rate
C. Extramedullary hematopoiesis

C. The production of hematopoietic cells in sites outside of the bone marrow can be referred to as myeloid metaplasia or
extramedullary hematopoiesis. Hematopoiesis, with the exception of lymphopoiesis, is normally confined to the bone
marrow during postnatal life. Production of erythroid, myeloid, and megakaryocytic elements can be established in the
liver and spleen, similar to that which occurs during embryonic development. Myeloid metaplasia is frequently associated
with myelofibrosis, a condition in which the marrow is gradually replaced by fibrotic tissue.
Myeloid metaplasia refers to

A. Displacement of normal marrow cells by fibrous tissue

B. Hematopoietic failure
C. Extramedullary hematopoiesis
D. Tumors (neoplasms) of the bone marrow
A. Lymphadenopathy is the most common presenting symptom.

A. Prominent lymphadenopathy is the most consistent finding in non-Hodgkin types of lymphoma at presentation, but
lymphoma may also arise in the spleen, liver, or GI tract (abdominal tumor). Lymphomas begin as localized tumors
involving lymphoid tissue that spread to the bone marrow and blood (depends on type). The malignant lymphoid cells are
immunologically classified as B cell (most common) or T/NK cell. Clonality can also be established by demonstrating gene
rearrangements via molecular analysis. Some common subtypes of non-Hodgkin lymphoma are small lymphocytic,
Burkitt, follicular, and mantle cell lymphomas. Leukemias are initially systemic disorders primarily involving the bone
marrow and blood at onset. Bone lesions are associated with multiple myeloma
Which of the following statements about non-Hodgkin types of lymphoma is true?

A. Lymphadenopathy is the most common presenting symptom.

B. Initially, they present as a systemic disease rather than a localized tumor.
C. They are often associated with multiple bone lesions.
D. They are characterized by proliferation of malignant cells primarily involving the bone marrow.

B. Potassium ferricyanide and potassium cyanide

B. The standard assay for hemoglobin utilizes potassium ferricyanide. This solution, formerly called Drabkin's reagent, is
now called cyanmethemoglobin (HiCN) reagent. The ferricyanide oxidizes hemoglobin iron from ferrous (Fe2+) to ferric
(Fe3+), and the potassium cyanide stabilizes the pigment as cyanmethemoglobin for spectrophotometric measurement
What combination of reagents is used to measure hemoglobin?

A. Hydrochloric acidHct (%) and p-dimethylaminobenzaldehyde

B. Potassium ferricyanide and potassium cyanide
C. Sodium bisulfite and sodium
metabisulfite
D. Sodium citrate and hydrogen peroxide
B. A2, C,E, and O

B. The band containing hemoglobin A2 is the slowest-migrating, staying closest to the cathode. The band containing
hemoglobin A has a net negative charge at an alkaline pH, and it moves the farthest toward the anode. An adult patient
without a hemoglobinopathy will have only these two bands appearing on a cellulose acetate electrophoresis.
The slowest-moving hemoglobin(s) on an alkaline electrophoresis at pH 8.6 is(are)
A. A
B. A2, C,E, and O
C. F
D. S, D, andG
C. Patient has hemoglobin AD or AG, and both procedures are correct

C. Hemoglobins S, D, and G all migrate to the same location on the hemoglobin electrophoresis gel at an alkaline pH.
However, because hemoglobins D and G are nonsickling hemoglobins, tests based on sickle formation under decreased
oxygen tension will have negative results. These hemoglobins can be further differentiated by their movement on agar gel
at an acid pH, whereas hemoglobins D and G will migrate with hemoglobin A, not with hemoglobin S.
A patient with suspected sickle cell trait has negative solubility test results, but hemoglobin electrophoresis at pH 8.6
shows an apparent A-S pattern. What is the most likely explanation?

A. Patient has hemoglobin AS, and the solubility test is incorrect.

B. Patient has hemoglobin AA, and the electrophoresis is incorrect.
C. Patient has hemoglobin AD or AG, and both procedures are correct.
D. Tests need to be repeated; impossible to determine which procedure is correct.
C. Sickle cell trait can be differentiated from sickle cell anemia with this test

C. When the sample is deoxygenated, reduced hemoglobin S polymerizes, resulting in a cloudy solution. A false negative
can be obtained if the quantity of hemoglobin S is below the sensitivity of the method, which can be seen in newborns and
anemic patients. Although this procedure is a screening test for hemoglobin S detection, it is positive in the presence of
any sickling hemoglobin, such as hemoglobin C Harlem.
Which of the following is an incorrect statement about the solubility test for Hemoglobin S?

A. Hemoglobin S polymerizes when deoxygenated.

B. Testing performed on a 2-day-old infant can result in a false negative result.
C. Sickle cell trait can be differentiated from sickle cell anemia with this test.
D. The test is positive in hemoglobin ^Harlem
A. Column used is slanted.

A. A slanted column increases the ESR. A clotted sample, which lacks fibrinogen, causes a falsely decreased ESR.
Fibrinogen is the plasma protein that most greatly affects the ESR. The EDTA tube for ESR must be at least half-full, and
the test must be set up within 4 hours of draw; failure to follow these guidelines results in poikilocytosis that will inhibit
rouleaux formation.
Which of the following is not associated with causing a falsely low ESR?

A. Column used is slanted.

B. EDTA tube is clotted.
C. EDTA tube is one-third full.
D. EDTA specimen is 24 hours old.
C. 330X109/L

C. Some patients develop EDTA-dependent platelet agglutinins caused by an IgM or IgG platelet-specific antibody. To
correct for this, the sample can be redrawn in sodium citrate and rerun. The dilution factor of blood to anticoagulant in
sodium citrate is 9:1. To compensate for the 10% dilutional loss of platelets, the platelet count obtained must be multiplied
by 1.1 (300 X 109/LX1.1=330X109/L).
A platelet count is performed on an automated instrument from an EDTA blood sample. Smear evaluation reveals the
presence of platelet clumps. The specimen is redrawn using sodium citrate as the anticoagulant, and a count of 300 X
109/L is obtained. What is the correct platelet count to report?

A. 270X109/L
B. 300X109/L
C. 330X109/L
D. 360X109/L
B. 5

B. Blood smears should be made within 5 hours of collection from blood anticoagulated with EDTA. Although some of the
blood cells may still be normal in blood kept longer, others (especially granulocytes) may deteriorate. Vacuolation of
neutrophils can appear as an artifact in blood kept past this time. The age of the blood may also affect the visual quality
when the slide is stained.
To best preserve cellular morphology, differential smears from an EDTA specimen should be made no more than hour(s)
after collection.

A. 1
B. 5
C. 12
D. 24
A. Decrease the angle of the spreader slide

A. Decreasing the angle will produce a longer, thinner smear. Increasing the angle or using a smaller drop of blood will
produce a shorter, thicker smear. The angle normally used for the spreader slide when making a smear is 30^5 degrees.
The blood smear made on a patient with polycythemia vera is too short. What should be done to correct this problem?

A. Decrease the angle of the spreader slide.

B. Increase the angle of the spreader slide.
C. Adjust the angle of the spreader slide to 45 degrees.
D. Use a smaller drop of blood.
D. Methylene blue and eosin

D. One type of Romanowsky stain is the Wright's stain. It is a polychrome stain consisting of methylene blue and eosin.
This combination causes multiple colors to appear on staining. Another commonly used Romanowsky stain is the
Wright's-Giemsa stain. Brilliant green and neutral red are used in a supravital stain for Heinz bodies. Crystal violet and
safranin are used in Gram's stain for bacteria.
The components of Wright's stain include

A. Crystal violet and safranin

B. Brilliant green and neutral red
C. New methylene blue and carbolfuchsin
D. Methylene blue and eosin
C. The stain or buffer is too acidic

C. When red blood cells are stained correctly with Wright's stain, their color is pink to orangered. They will appear bright
red in the presence of an acid buffer and stain. Staining elements such as white cells, which stain with a more basic pH,
will not take up the stain adequately in this instance. Inadequate washing and an alkaline stain or buffer mixture results in
a smear that is excessively blue.
What is the reason for red blood cells to be bright red and the WBC nuclei to be poorly stained when using Wright's stain?

A. The staining time is too long.

B. The stain or buffer is too alkaline.
C. The stain or buffer is too acidic.
D. The smear was not washed long enough.
C. 6.0%

C. The formula for calculating a reticulocyte count in percent is

(Number of reticulocytes counted/ Total number of RBCs counted) X100
In the case described in question 233,

%Reticulocytes = (60/1000) X 100 = 6.0%

Because the error in reticulocyte counts is high, it is desirable to count a larger number of cells or use a standardized
counting method such as the Miller disk.
If 60 reticulocytes are counted in 1000 red blood cells, what is the reticulocyte count?

A. 0.06%
B. 0.6%
C. 6.0%
D. 60.0%
C. 180X109/L

C. The formula used to calculate the absolute

reticulocyte count is
Reticulocyte percent
100
X RBC (1012/L) X 1000
Multiplication by 1000 is done to report the
results in SI units of 109/L.
In this case,
6.0 X 3.00
100 X 1000 = 180 X 109/L
180 X 103/uL is not expressed in SI units.
Using the percent reticulocyte from question 233 and an RBC count of 3.00 X 1012/L (3.00 X 106/|xL), the calculated
absolute reticulocyte count reported in SI units is

A. 1.8X109/L
B. 18X109/L
C. 180X109/L
D. 180X103/(JLL
B. Lipids

B. As visualized in Color Plate 19«, Sudan black B is a cytochemical stain for lipids, including steroids, phospholipids, and
neutral fats. It is widely used as a tool to differentiate the blasts of acute lymphoblastic leukemia (ALL) from those of acute
myelogenous leukemia (AML). Blasts in ALL are SBB negative, whereas those in AML will show some degree of
positivity.
The Sudan black B stain shown in Color Plate 19 is a stain for

A. Glycogen
B. Lipids
C. Myeloperoxidase
D. Acid phosphatase
C. 200

C. An LAP score is determined by first multiplying the number of cells found by the degree
of positivity (i.e., 20 X 1 = 20). These numbers are then added together to obtain a final score. In this instance, 0 + 20 +
60 + 60 + 60 = 200
The following numbers were obtained in evaluating leukocyte alkaline phosphatase (LAP) activity in neutrophils. What is
the score?
0 -15
1 - 20
2 - 30
3 - 20
4 - 15

A. 100
B. 115
C. 200
D. 215
C. Iron

C. When stained with a mixture of potassium ferricyanide and hydrochloric acid, nonheme iron stains bright blue. This is
the most common stain used for storage iron. It can be used on bone marrow to identify sideroblasts, peripheral blood to
identify the presence of siderocytes, or urine to perform hemosiderin testing
Perl's Prussian blue is a stain used to detect

A. DNA
B. RNA
C. Iron
D. Glycogen
C. Pappenheimer bodies

C. Pappenheimer bodies are iron deposits associated with mitochondria, and they stain with both Perl's Prussian blue and
Wright's stain. A cell that contains Pappenheimer bodies is called a siderocyte. Howell-Jolly bodies and basophilic
stippling can be visualized with Wright's stain, whereas Heinz bodies require a supravital stain to be seen.
Which of the following red cell inclusions stain with both Perl's Prussian blue and Wright's stain?

A. Howell-Jolly bodies
B. Basophilic stippling
C. Pappenheimer bodies
D. Heinz bodies
B. 0.10mm

B. Depth on a standard counting chamber is 0.10 mm. The formula to calculate volume is V= A X D, where V is volume, A
is area, and D is depth. When the counting chamber is used, the area may change, depending on the number of ruled
squares counted, but the depth remains constant.
What is the depth between the counting platform and the coverslip on a hemacytometer?

A. 0.01mm
B. 0.10mm
C. 1.00mm
D. 0.1 cm
B. 7.7X109/L

B. The standard formula for hemacytometer counts expressed in mm3 is

Total number cells counted X dilution factor
Area counted X depth
In this instance,
308 X 20 _ 6160
8 mm2 X 0.10 mm 0.8 mm3
= 7700/mm3
= 7.7 X 109/L
A WBC count is performed on a hemacytometer using a 1:20 dilution. 308 cells are seen in a total area of 8 mm2. What is
the WBC count?

A. 3.8X109/L
B. 7.7X109/L
C. 15.4X109/L
D. 38.5X109/L
B. 2.75 - 9.5 - 24.8

B. The Rule of Three states that RBC X 3 = Hgb and Hgb X 3 = Hct ±3 in error-free results. These rules apply only for
normocytic, normochromic erythrocytes. One check to determine if an error has occurred is to determine the MCHC. An
MCHC should be less than 37.0 g/dL in error-free results. The MCHC is calculated by dividing hemoglobin by hematocrit
and multiplying by 100. In instance (B), the MCHC is 38.3 g/dL and the Rule of Three is broken. All other answers follow
the Rule of Three
Which set of results indicates that an error in measurement has occurred?
RBC x 10^12/L - Hgb (g/dL) - Hct (%)

A. 2.50 - 7.6 - 22.9

B. 2.75 - 9.5 - 24.8
C. 3.40 - 10.0 - 31.0
D. 3.75 - 11.1 - 34.0
A. Hereditary spherocytosis

A. The only true cause of a high MCHC is the presence of spherocytes, as may be seen in hereditary spherocytosis.
Because the MCHC is a calculation using the hemoglobin and hematocrit, anything causing those parameters to be wrong
will affect the MCHC. The occurrence of a falsely high MCHC is much more common than the presence of spherocytes,
and specimen troubleshooting procedures must be undertaken to obtain reportable results.
Which of the following would not be the cause of a falsely high MCHC of 38.3 g/dL on an automated instrument?

A. Hereditary spherocytosis
B. Lipemia
C. Presence of a cold agglutinin
D. Instrument sampling or mixing error
C. Interruption of an electrical current by cells

C. Blood cells are nonconductors of electrical current; they create a resistance/impedance of current in a diluent solution
that is conductive. When the suspension is forced through a small aperture, the current flow is interrupted by the presence
of the cells. A pulse is generated. The number of pulses generated is proportional to the number of particles present, and
the size of the pulse generated is proportional to the size of the cell.
What is the principle of automated impedance cell counters?

A. Angle of laser beam scatter by cells

B. Amplification of an electrical current by cells
C. Interruption of an electrical current by cells
D. Change in optical density of the solution containing cells
C. ±2.0

C. Using ±2 s, 95% confidence limits are achieved; 95% confidence limits predict a range that values should fall within
95% of the time. For example, if a WBC count is 12.0 X 109/L with 2 s of ±0.5, then a succeeding count must be less than
11.5 X 109/L or greater than 12.5 X 109/L to be considered significantly different
A clinically significant difference between two electronic cell counts is indicated when the standard deviation is greater
than

A. ±1.0
B. ±1.5
C. ±2.0
D. ±3.0
B. Cytoplasmic granularity

B. Side angle scatter of a laser beam increases with granularity of the cytoplasm. Forward angle scatter is used to
determine relative size. The number of signals is proportional to the number of cells. The presence of specific antigens in
the cytoplasm or on the cell surface is determined by immunofluorescence after reactions with appropriate antibodies.
Side angle scatter in a laser-based cell counting system is used to measure

A. Cell size
B. Cytoplasmic granularity
C. Cell number
D. Immunologic (antigenic) identification
A. Falsely increased because of nRBCs

A. An impedance counter cannot differentiate between the nucleus of a white blood cell and the nucleus of an nRBC. Both
will be counted as WBCs. The presence of 5 or more nRBCs/100 WBCs can result in a falsely elevated white blood cell
count, and a correction must be made
as follows:
Corrected WBC count =
Observed count X 100
100 + # nRBCs/100 WBCs
A white blood cell count is done on an automated impedance cell counter from a patient with the blood picture seen in
Color Plate 4. The WBC count is most likely

A. Falsely increased because of nRBCs

B. Falsely increased because of red cell fragments
C. Falsely decreased because of nRBCs
D. Accurate; no error with this methodology
D. Beta-thalassemia minor

D. Hemoglobin A2 values up to 3.5% are considered normal. Values between 3.5 and 8.0% are indicative of beta
thalassemia minor. Hemoglobins C, E, and O have net electrical charges similar to hemoglobin A2. They elute off with
hemoglobin A2 using anion exchange (column) chromatography, causing an invalid hemoglobin A2 result. If the
hemoglobin A2 quantification using column chromatography yields a result greater than 8.0%, one of these interfering
hemoglobins should be considered.
The hemoglobin A2 quantification using anion exchange chromatography will be valid in

A. Hemoglobin C disease
B. Hemoglobin E trait
C. Hemoglobin O trait
D. Beta-thalassemia minor
A. Beta-thalassemia major
A. Any condition with spherocytes can cause an increased osmotic fragility, dependent on the number of spherocytes
present. Spherocytes are seen in hereditary spherocytosis, immune hemolytic anemias, and severe burns. Target cells,
associated with thalassemias and hemoglobinopathies, have an increased surface area-to-volume ratio and a decreased
osmotic fragility.
Which of the following is not associated with an increased osmotic fragility and a decreased surface area-to-volume ratio?

A. Beta-thalassemia major
B. Hereditary spherocytosis
C. Warm autoimmune hemolytic anemia
D. Burn victims
B. Solubility test for hemoglobin S

B. The solubility test for hemoglobin S is not quantitative; it is reported as positive or negative. A clotted specimen will not
affect the result. A clotted specimen will falsely decrease the other tests listed: ESR due to low fibrinogen, hematocrit due
to a false low RBC count, and platelets are trapped in the clot.
A clotted EDTA tube can be used to perform a(n)

A. Erythrocyte sedimentation rate

B. Solubility test for hemoglobin S
C. Hematocrit
D. Platelet count
A. Reference interval

A. Hematology reference intervals are available in many textbooks. They are influenced by patient population,
instrumentation, and reagents used. Therefore, it is ideal for each laboratory to establish its own reference intervals. The
reference interval excludes the upper and lower 2.5% of the values. The remaining 95% represent the reference
interval.
The test value range that includes 95% of the normal population is the

A. Reference interval
B. Linearity limit
C. Reportable range
D. Critical range
C. Certified standards are used

C. Standards are commercially available to generate a hemoglobin concentration curve. The absorbance of each solution
is read against a reagent blank at 540 nm on a spectrophotometer. Patient blood samples and commercial control
materials can be used to assess precision and other quality control parameters.
To establish a standard curve for reading hemoglobin concentration,

A. A commercial control material is used.

B. A wavelength of 640 nm is employed.
C. Certified standards are used.
D. A patient blood sample of known hemoglobin concentration is used.
A. Excessive anticoagulant

A. Anything that causes an increase in absorbance will cause a hemoglobin that is read spectrophotometrically to be
falsely high. It is necessary to correct for this type of error, such as making a plasma blank in the case of lipemia or
icterus. WBCs are present in the hemoglobin dilution and usually do not interfere. When the WBC count is extremely high,
their presence will cause cloudiness, increasing the absorbance in the hemoglobin measuring cell and resulting in a
falsely high hemoglobin concentration. Excessive anticoagulant does not affect hemoglobin
readings.
Which of the following is not a source of error when measuring hemoglobin by the cyanmethemoglobin method?

A. Excessive anticoagulant
B. White blood cell count that exceeds linearity limits
C. Lipemic plasma
D. Scratched or dirty hemoglobin measuring cell
A. Excessive centrifugation causes falsely low results

A. When a microhematocrit is spun at 10,000-15,000 X g for 5 minutes, maximum packing is achieved. Spinning a longer
time has no affect on the result. A tube that is not full causes RBC shrinkage and a falsely decreased hematocrit.
Hemolysis damages the RBC membrane and allows for more packing. Trapped plasma is present when optimal packing
is not achieved due to inadequate speed or time of centrifugation, causing a falsely high hematocrit.
Which of the following statements about
microhematocrits is false?
A. Excessive centrifugation causes falsely low results.
B. A tube less than half full causes falsely
low results.
C. Hemolysis causes falsely low results.
D. Trapped plasma causes falsely high
results.
C. Hemoglobin content of the red blood cells

C. The erythrocyte sedimentation rate (ESR) measures the rate of fall of red cells through plasma. ESR increases when
cells become stacked (rouleaux, as seen in Color Plate 20). ESR decreases when cells are not normal discocytes. Larger
cells (macrocytes) and fewer cells (anemia) fall faster. Plasma containing increased proteins, such as fibrinogen and
globulins, promote rouleaux formation and an elevated ESR. Hemoglobin content does not affect the ESR.
The erythrocyte sedimentation rate (ESR) is influenced by the red cell phenomenon seen in Color Plate 20. Which of the
following factors will neither contribute to this phenomenon
nor affect the ESR?

A. Size of the red blood cells

B. Shape of the red blood cells
C. Hemoglobin content of the red blood cells
D. Composition of the plasma
A. Nucleated RBCs

A. Impedance counters measure RBCs and platelets using the same dilution. To differentiate the two, sizing thresholds
are used. Particles between 2 and 20 fL are counted as platelets, and particles larger than 35 fL are counted as RBCs.
Small RBCs, clumped platelets, and giant platelets fall in the overlap area between platelets and RBCs, generating a
warning flag. Nucleated RBCs are larger than normal RBCs and are not mistaken for platelets.
255. An EDTA blood sample run on an automated impedance cell counter has generated a warning flag at the upper
region of the platelet histogram illustrated below. Which of the following would not be a cause of this warning flag?

A. Nucleated RBCs
B. Microcytic RBCs
C. EDTA-dependent platelet agglutinins
D. Giant platelets
C. 8-20

C. A platelet estimate is obtained by multiplying the average number of platelets per oil immersion field (in an erythrocyte
monolayer) by 20,000. The reference range for a platelet count is 150^50 X 109/L. Approximately 8-20 platelets per oil
immersion field will represent a normal platelet concentration of approximately 160^00 X 109/L. This method assumes the
red blood cell count is normal. If it is not, alternate platelet estimate procedures may need to be performed.
To evaluate normal platelet numbers in an appropriate area of a blood smear, approximately how many platelets should
be observed per oil immersion field?

A. 1-4
B. 4-10
C. 8-20
D. 20-50
D. An erythrocyte must have at least 4 blue particles to be counted as a reticulocyte

D. A living cell stain using new methylene blue is performed for reticulocyte counts. Reticulocytes should not be stained
for less than 5 minutes. Howell-Jolly bodies, Pappenheimer bodies, crenated cells, and refractile artifact can be mistaken
for reticulocyte inclusions. Two or more particles of reticulum constitute a reticulocyte.
Which of the following statements about manual reticulocyte counts is false?

A. The blood/stain mixture is incubated for 5-10 minutes.

B. New methylene blue, a supravital stain, is used.
C. RBC inclusions can result in falsely elevated counts.
D. An erythrocyte must have at least 4 blue particles to be counted as a reticulocyte.
B. After replacement of any major part

B. All accredited laboratories are required to perform calibration with commercially available calibrators at least once
every 6 months. Calibration must be checked if any major part is replaced or if optical alignment is adjusted. A calibration
procedure can be verified using commercially
available controls.
When are automated cell counters required to have a calibration check performed?

A. At least every 3 months

B. After replacement of any major part
C. After performing monthly maintenance
D. When the control values are greater than 2 standard deviations from the mean
A. Perform a saline replacement procedure.

A. An MCHC >37.0 g/dL is most likely caused by an error in measurement. In this instance, the Rule of Three shows that
the RBC X 9 matches the hematocrit, but the RBC X 3 does not match the hemoglobin. The hemoglobin does not match
either the RBC or hematocrit. This indicates a hemoglobin problem, and it can be corrected with a saline replacement
procedure. This specimen may be lipemic or icteric. Warming the specimen is useful in troubleshooting a high MCHC due
to a cold agglutinin. A microhematocrit would be indicated if the hematocrit result was invalid.
A blood sample was run through an automated cell counter and the following results were obtained: WBC 6.9 X 109/L (6.9
X 103/(JiL), RBC 3.52 X 1012/L (3.52 X 106/|xL), Hgb 120 g/L (12.0 g/dL), Hct 0.32 L/L (32.0%), MCH 34.1 pg, MCHC
37.5 g/dL. Which of the troubleshooting steps that follows should be performed to obtain reportable results?

A. Perform a saline replacement procedure.

B. Warm the specimen to 37°C and rerun.
C. Perform a microhematocrit.
D. None; the results are reportable
A. Hemoglobin only

A. Hemoglobin is valid on a hemolyzed specimen, because RBC lysis is the first step in the cyanmethemoglobin method.
The red blood cell count depends on the presence of intact red blood cells. Red blood cell fragments caused by hemolysis
may be as small as platelets and affect instruments that use sizing criteria to differentiate the two. Therefore, samples for
these procedures should be re-collected.
Which of the following tests could be performed on a hemolyzed blood sample?

A. Hemoglobin only
B. Hemoglobin and platelet count
C. RBC count and hematocrit
D. No results would be reportable.
D. Osmotic fragility

D. Heparin is recommended for osmotic fragility and red cell enzyme studies, because it results in less lysis and less
membrane stress than other anticoagulants. Heparin induces platelet clumping and is unacceptable for the platelet count.
Heparin is unacceptable for coagulation test procedures because it binds with antithrombin to neutralize many enzymes,
especially thrombin. This would cause very long coagulation test results. EDTA is recommended for most routine
hematology procedures, especially for Wright's-stained smears. Sodium citrate or EDTA can be used for sedimentation
rates.
For which of the following procedures would heparin be a recommended anticoagulant?

A. Platelet count
B. Coagulation tests
C. Smear-based red cell morphology
D. Osmotic fragility
A. Platelets appear dark against a light background.

A. When counting platelets, the center square (1 mm2) is counted on each side of the hemacytometer. Platelets appear
round or oval and may have dendrites. These characteristics can help distinguish them from debris, which is irregularly
shaped and often refractile. White cells are not lysed; they may be counted, using a different ruled area of the
hemacytometer. Platelets will be easier to count if allowed to settle for 10 minutes, because they will have settled into one
plane of focus.
In the platelet count procedure using phase microscopy,
A. Platelets appear dark against a light background.
B. The entire ruled counting surface of the hemacytometer is used.
C. Ammonium oxalate will lyse the WBCs.
D. Platelets should be counted immediately after plating the hemacytometer.
B. Precision

B. "Precision" is the term used to describe the reproducibility of a method that gives closely similar results when one
sample is run multiple times. An accurate method is one that gives results that are very close to the true value.
Laboratories must have procedures that are both accurate and precise.
What is the quality control term used to describe the reproducibility of a test?

A. Accuracy
B. Precision
C. Standard deviation
D. Specificity

C. 16.7

C. WBC counts done by an impedance cell counter must be corrected when nucleated red blood cells (nRBCs) are
present (see Color Plate 4), because such instruments do not distinguish between white and red nucleated cells.
This correction is done according to the following
formula:
Corrected WBC count =
Observed count X 100/ 100 + # nRBCs per 100 WBCs
In this instance,
35.0 X 100/(100 + 110)
= 16.7 X 109/L
Use the following information to answer questions 264-268.
The peripheral blood shown in Color Plate 4 is from a 10-month-old Greek boy with the following results on an automated
impedance counter:
WBC 35.0 X 109/L (35.0 X 103/(xL); RBC 2.50 x 1012/L (2.50 x 106/uL); hemoglobin 45 g/L (4.5 g/dL); hematocrit 0.16
L7L (16%); platelet count 250 X 109/L (250,000/(jLl_); reticulocyte count 8.0%; 110 nucleated red blood cells/100 WBCs
and many targets are seen.
Other laboratory results are as follows: serum iron elevated; total iron-binding capacity (TIBC) decreased; serum ferritin
elevated.

264. What is the corrected white blood cell count expressed in SI units of X109/L?

A. 4.6
B. 12.5
C. 16.7
D. 18.4
A. Microcytic, hypochromic

A. The appearance of red cells on a differential

smear may be predicted by calculating the red
cell indices.
MCV =
(Hct X 10)/RBC = (16% X 10) /2.50 X 10U/L
= 64.0 fL
MCH
(Hgb X 10)/ RBC = 4.5 g/dL X 10/ 2.50 X 10"/L
= 18.0 pg
MCHC =
(Hgb X 100)/Hct = (4.5 g/dL X 100)/16%
=28.1 g/dL (281 g/L)
The mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin
concentration (MCHC) are al below the reference range. This indicates a cell that is small (microcytic) with a reduced
hemoglobin concentration (hypochromic). These indices refer to averages and do not necessarily reflect the actual
appearance of cells in which there is great diversity in size and shape.
265. What would be the appearance of the child's red blood cells on a peripheral smear?

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