CHAPTER
Hematopathology of Red Blood
Cells and Bleeding Disorders
PBD9 Chapter 14 and PBD8 Chapter 14: Red Blood Cell and Bleeding Disorders
BP9 Chapter 11 and BP8 Chapter 12: Hematopoietic and Lymphoid Systems
1 A 77-year-old woman notices that small, pinpoint-to-
blotchy areas of superficial hemorrhage have appeared on
her gums and on the skin of her arms and legs over the past
3 weeks. On physical examination, she is afebrile and has no
organomegaly. Laboratory studies show a normal prothrom-
bin time and partial thromboplastin time. CBC shows hemo-
globin of 12.7 g/dL, hematocrit of 37.2%, MCV of 80 μm3,
platelet count of 276,000/mm3, and WBC count of 5600/mm3.
Platelet function studies and fibrinogen level are normal, and
no fibrin split products are detectable. Which of the following
conditions best explains these findings?
A Chronic renal failure
B Macronodular cirrhosis
C Meningococcemia
D Metastatic carcinoma
E Vitamin C deficiency
2 A healthy 19-year-old woman suffered blunt abdominal
trauma in a motor vehicle accident. On admission to the hos-
pital, her initial hematocrit was 33%, but over the next hour,
it decreased to 28%. A paracentesis yielded serosanguineous
fluid. She was taken to surgery, where a liver laceration was
repaired, and 1 L of bloody fluid was removed from the peri-
toneal cavity. She remained stable. A CBC performed 3 days
later is most likely to show which of the following morpho-
logic findings in the peripheral blood?
A Basophilic stippling of red cells
B Hypochromic red cells
C Leukoerythroblastosis
D Reticulocytosis
E Schistocytosis
3 A 65-year-old man has experienced worsening fatigue
for the past 5 months. On physical examination, he is afebrile
and has a pulse of 91/min, respirations of 18/min, and blood
14
pressure of 105/60 mm Hg. There is no organomegaly. A
stool sample is positive for occult blood. Laboratory findings
include hemoglobin of 5.9 g/dL, hematocrit of 18.3%, MCV
of 99 μm3, platelet count of 250,000/mm3, and WBC count of
7800/mm3. The reticulocyte concentration is 3.9%. No fibrin
split products are detected, and direct and indirect Coombs
test results are negative. A bone marrow biopsy specimen
shows marked erythroid hyperplasia. Which of the following
conditions best explains these findings?
A Aplastic anemia
B Autoimmune hemolytic anemia
C Chronic blood loss
D Iron deficiency anemia
E Metastatic carcinoma
4 During the past 6 months, a 25-year-old woman has
noticed a malar skin rash that is made worse by sun exposure.
She also has had arthralgias and myalgias. On physical exami-
nation, she is afebrile and has a pulse of 100/min, respirations
of 20/min, and blood pressure of 100/60 mm Hg. There is ery-
thema of skin over the bridge of the nose. No organomegaly is
noted. Laboratory findings include positive serologic test re-
sults for ANA and double-stranded DNA, hemoglobin of 8.1
g/dL, hematocrit of 24.4%, platelet count of 87,000/mm3, and
WBC count of 3950/mm3. The peripheral blood smear shows
nucleated RBCs. A dipstick urinalysis is positive for blood, but
there are no WBCs, RBCs, or casts seen on microscopic exami-
nation of the urine. Which of the following laboratory findings
is most likely to be present?
A Decreased haptoglobin
B Decreased iron
C Decreased reticulocytosis
D Elevated D dimer
E Elevated hemoglobin F
F Elevated protoporphyrin
205
206 UNIT II Diseases of Organ Systems
5 A 28-year-old woman has had a constant feeling of leth-
argy since childhood. On physical examination, she is afebrile
and has a pulse of 80/min, respirations of 15/min, and blood
pressure of 110/70 mm Hg. The spleen tip is palpable, but
there is no abdominal pain or tenderness. Laboratory stud-
ies show hemoglobin of 11.7 g/dL, platelet count of 159,000/
mm3, and WBC count of 5390/mm3. The peripheral blood
smear shows small round erythrocytes that lack a zone of cen-
tral pallor. An inherited abnormality in which of the following
RBC components best accounts for these findings?
A α-Globin chain
B β-Globin chain
C Carbonic anhydrase
D Glucose-6-phosphate dehydrogenase
E Heme with porphyrin ring
F Spectrin cytoskeletal protein
  
6 A 13-year-old boy has the sudden onset of severe ab-
dominal pain and cramping accompanied by chest pain, non-
productive cough, and fever. On physical examination, his
temperature is 39° C, pulse is 110/min, respirations are 22/min,
and blood pressure is 80/50 mm Hg. He has diffuse abdominal
tenderness, but no masses or organomegaly. Laboratory studies
show a hematocrit of 18%. The peripheral blood smear is shown
in the figure. A chest radiograph shows bilateral pulmonary in-
filtrates. Which of the following is the most likely mechanism
for initiation of his pulmonary problems?
A Chronic hypoxia of the pulmonary parenchyma
B Defects in the alternative pathway of complement
activation
C Extensive RBC adhesion to endothelium
D Formation of autoantibodies to alveolar basement
membrane
E Intravascular antibody-induced hemolysis
7 An 18-year-old woman from Copenhagen, Denmark,
has had malaise and a low-grade fever for the past week, along
with arthralgias. On physical examination, she appears very
pale, except for a bright red malar facial rash. She has a history
of chronic anemia, and spherocytes are observed on a peri­
pheral blood smear. Her hematocrit, which normally ranges
from 35% to 38%, is now 28%, and the reticulocyte count is
very low. The serum bilirubin level is 0.9 mg/dL. Which of
the following events is most likely to have occurred in this
patient?
A Accelerated extravascular hemolysis in the spleen
B Development of anti-RBC antibodies
C Disseminated intravascular coagulation
D Reduced erythropoiesis from parvovirus infection
E Superimposed dietary iron deficiency
8 A clinical study of patients who inherit mutations that
reduce the level of ankyrin, the principal binding site for spec-
trin, in the RBC membrane cytoskeleton shows an increased
prevalence of chronic anemia with splenomegaly. For many
patients, it is observed that splenectomy reduces the severity
of anemia. This beneficial effect of splenectomy is most likely
related to which of the following processes?
A Decrease in opsonization of RBCs and lysis in
spleen
B Decrease in production of reactive oxygen species
by splenic macrophages
C Decrease in splenic RBC sequestration and lysis
D Increase in deformability of RBCs within splenic
sinusoids
E Increase in splenic storage of iron
9 A 3-year-old boy from Sicily has a poor appetite and
is underweight for his age and height. Physical examination
shows hepatosplenomegaly. The hemoglobin concentration is
6 g/dL, and the peripheral blood smear shows severely hy-
pochromic and microcytic RBCs. The total serum iron level is
normal, and the reticulocyte count is 10%. A radiograph of the
skull shows maxillofacial deformities and expanded marrow
spaces. Which of the following is the most likely cause of this
child’s illness?
A Imbalance in α-globin and β-globin chain
production
B Increased fragility of erythrocyte membranes
C Reduced synthesis of hemoglobin F
D Relative deficiency of vitamin B12
E Sequestration of iron in reticuloendothelial cells
10 A 10-year-old child has experienced multiple episodes
of pneumonia and meningitis with septicemia since infancy.
Causative organisms include Streptococcus pneumoniae and
Haemophilus influenzae. On physical examination, the child
has no organomegaly and no deformities. Laboratory studies
show hemoglobin of 9.2 g/dL, hematocrit of 27.8%, platelet
count of 372,000/mm3, and WBC count of 10,300/mm3. A he-
moglobin electrophoresis shows 1% hemoglobin A2, 7% he-
moglobin F, and 92% hemoglobin S. Which of the following is
the most likely cause of the repeated infections in this child?
A Absent endothelial cell expression of adhesion
molecules
B Diminished hepatic synthesis of complement
proteins
C Impaired neutrophil production
D Loss of normal splenic function
E Reduced synthesis of immunoglobulins
 CHAPTER 14 Hematopathology of Red Blood Cells and Bleeding Disorders
11 A 32-year-old woman from Hanoi, Vietnam, gives birth
at 34 weeks’ gestation to a markedly hydropic stillborn male
infant. Autopsy findings include hepatosplenomegaly and
cardiomegaly, serous effusions in all body cavities, and gen-
eralized hydrops. No congenital anomalies are noted. There
is marked extramedullary hematopoiesis in visceral organs.
Which of the following hemoglobins is most likely predomi-
nant on hemoglobin electrophoresis of the fetal RBCs?
A Hemoglobin A1
B Hemoglobin A2
C Hemoglobin Bart’s
D Hemoglobin E
E Hemoglobin F
F Hemoglobin H
  
12 A 17-year-old girl has had a history of fatigue and weak-
ness for her entire life. She has not undergone puberty. On
physical examination, secondary sex characteristics are not
well developed. She has hepatosplenomegaly. CBC shows he-
moglobin of 9.1 g/dL, hematocrit of 26.7%, MCV of 66 μm3,
platelet count of 89,000/mm3, and WBC count of 3670/mm3.
The appearance of the peripheral blood smear is shown in the
figure. Additional laboratory findings include serum glucose
of 144 mg/dL, TSH of 6.2 mU/mL, and ferritin of 679 ng/mL.
A mutation in a gene encoding for which of the following is
most likely to be present in this girl?
A Ankyrin
B β-Globin
C G6PD
D HFE
E NADPH oxidase
13 A 12-year-old boy has a history of episodes of severe ab-
dominal, chest, and back pain since early childhood. On physi-
cal examination, he is afebrile, and there is no organomegaly.
Laboratory studies show hemoglobin of 11.2 g/dL, platelet
count of 194,000/mm3, and WBC count of 9020/mm3. The pe-
ripheral blood smear shows occasional sickled cells, nucleated
RBCs, and Howell-Jolly bodies. Hemoglobin electrophoresis
shows 1% hemoglobin A2, 6% hemoglobin F, and 93% hemo-
globin S. Hydroxyurea therapy is found to be beneficial in
this patient. An increase in which of the following is the most
likely basis for its therapeutic efficacy?
207
A Erythrocyte production
B Overall globin chain synthesis
C Oxygen affinity of hemoglobin
D Production of hemoglobin A
E Production of hemoglobin F
14 A 25-year-old woman has a 3-year history of arthralgias.
Physical examination shows no joint deformity, but she ap-
pears pale. Laboratory studies show total RBC count of 4.7
million/mm3, hemoglobin of 12.5 g/dL, hematocrit of 37.1%,
platelet count of 217,000/mm3, and WBC count of 5890/mm3.
The peripheral blood smear shows hypochromic and micro-
cytic RBCs. Total serum iron and ferritin levels are normal.
Hemoglobin electrophoresis shows 93% hemoglobin A1 with
elevated hemoglobin A2 level of 5.8% and hemoglobin F level
of 1.2%. What is the most likely diagnosis?
A Anemia of chronic disease
B Autoimmune hemolytic anemia
C β-Thalassemia minor
D Infection with Plasmodium vivax
E Iron deficiency anemia
15 A 23-year-old African-American man passes dark red-
dish brown urine 3 days after taking an anti-inflammatory
medication that includes phenacetin. He is surprised, because
he has been healthy all his life and has had no major illnesses.
On physical examination, he is afebrile, and there are no re-
markable findings. CBC shows a mild normocytic anemia, but
the peripheral blood smear shows precipitates of denatured
globin (Heinz bodies) with supravital staining and scattered
“bite cells” in the population of RBCs. Which of the following
is the most likely diagnosis?
A α-Thalassemia minor
B β-Thalassemia minor
C Glucose-6-phosphate dehydrogenase deficiency
D Sickle cell trait
E Abnormal ankyrin in RBC cytoskeletal membrane
F Warm antibody autoimmune hemolytic anemia
16 Since childhood, a 30-year-old man has been easily
fatigued with minimal exercise. Laboratory studies show
hypochromic microcytic anemia. Hemoglobin electrophoresis
reveals decreased Hgb A1 with increased Hgb A2 and Hgb F.
His serum ferritin is markedly increased. Which of the following
mutations is most likely to be present in the β-globin gene of
this man?
A New stop codon
B Single base insertion, with frameshift
C Splice site
D Three-base deletion
E Trinucleotide repeat
208 UNIT II Diseases of Organ Systems
17 A 16-year-old boy notes passage of dark urine. He has a
history of multiple bacterial infections and venous thromboses
for the past 10 years, including portal vein thrombosis in the
previous year. On physical examination, his right leg is swol-
len and tender. CBC shows hemoglobin, 9.8 g/dL; hematocrit,
29.9%; MCV, 92 μm3; platelet count, 150,000/mm3; and WBC
count, 3800/mm3 with 24% segmented neutrophils, 1% bands,
64% lymphocytes, 10% monocytes, and 1% eosinophils. He
has a reticulocytosis, and his serum haptoglobin level is very
low. A mutation affecting which of the following gene prod-
ucts is most likely to give rise to this clinical condition?
A β-Globin chain
B Factor V
C Glucose-6-phosphate dehydrogenase
D Phosphatidylinositol glycan A (PIGA)
E Prothrombin G20210A
F Spectrin
18 A 30-year-old, previously healthy man from Lagos,
Nigeria, passes dark brown urine 2 days after starting the
prophylactic antimalarial drug primaquine. On physical ex-
amination, he appears pale and is afebrile. There is no organo-
megaly. Laboratory studies show that his serum haptoglobin
level is decreased. Which of the following is the most likely
explanation of these findings?
A Antibody-mediated hemolysis
B Impaired DNA synthesis
C Impaired globin chain synthesis
D Increased susceptibility to complement-induced lysis
E Mechanical fragmentation of RBCs as a result of
vascular narrowing
F Oxidative injury to hemoglobin
G Reduced deformability of RBC membrane
19 A 34-year-old woman reports becoming increasingly tired
for the past 5 months. On physical examination, she is afebrile
and has mild splenomegaly. Laboratory studies show a hemo-
globin concentration of 10.7 g/dL and hematocrit of 32.3%. The
peripheral blood smear shows spherocytes and rare nucleated
RBCs. Direct and indirect Coombs test results are positive at
37° C, although not at 4° C. Which of the following underlying
diseases is most likely to be diagnosed in this patient?
A Escherichia coli septicemia
B Hereditary spherocytosis
C Infectious mononucleosis
D Mycoplasma pneumoniae infection
E Systemic lupus erythematosus
20 A 22-year-old woman has experienced malaise and a
sore throat for 2 weeks. Her fingers turn white on exposure
to cold. On physical examination, she has a temperature of
37.8° C, and the pharynx is erythematous. Laboratory find-
ings include a positive monospot (heterophile antibody) test
result. Direct and indirect Coombs test results are positive at
4° C, although not at 37° C. Which of the following molecules
bound on the surfaces of the RBCs most likely accounts for
these findings?
A α2-Macroglobulin
B Complement C3b
C Fibronectin
D Histamine
E IgE
21 A 65-year-old man diagnosed with follicular non-­Hodgkin
lymphoma is treated with chemotherapy. He develops fever and
cough of a week’s duration. On examination, there are bilateral
pulmonary rales. A chest radiograph shows diffuse interstitial in-
filtrates. A sputum specimen is positive for cytomegalovirus. He
develops scleral icterus and Raynaud phenomenon. Laboratory
studies show hemoglobin, 10.3 g/dL; hematocrit, 41.3%; MCV,
101 μm3; WBC count, 7600/mm3; and platelet count, 205,000/
mm3. His serum total bilirubin is 6 mg/dL, direct bilirubin is 0.8
mg/dL, and LDH is 1020 U/L. Coombs test is positive. Which of
the following is the most likely mechanism for his anemia?
A Marrow aplasia caused by chemotherapy
B Vitamin K deficiency caused by cytomegalovirus
hepatitis
C Megaloblastic anemia caused by folate deficiency
D Extravascular hemolysis caused by cold agglutinins
E Iron deficiency caused by metastases to colon
22 A 29-year-old woman has had fatigue with dizziness for
the past 5 months. On physical examination, she has an ery-
thematous malar rash. She has no lymphadenopathy, but there
is a palpable spleen tip. She is afebrile. Laboratory studies show
hemoglobin, 8.9 g/dL; hematocrit, 27.8%; MCV, 103 μm3; RBC
distribution width index, 22; WBC count, 8650/mm3; platelet
count, 222,000/mm3; and reticulocyte count, 3.3%. The periph-
eral blood smear shows polychromasia, but no schistocytes.
Her serum total bilirubin is 3.2 mg/dL with direct bilirubin
0.8 mg/dL, and haptoglobin is 5 mg/dL. Antinuclear antibody
and anti–double-stranded DNA tests are positive. What addi-
tional laboratory test finding is she most likely to have?
A D-dimer 10 μg/mL
B Increased RBC osmotic fragility
C Positive Coombs test
D Serum cobalamin (vitamin B12) 50 pg/mL
E Serum ferritin 240 ng/mL
23 A 29-year-old rugby player takes part in a particularly con-
tentious game between New Zealand and South Africa. He is the
forward prop in the scrums, hitting hard and being hit hard by
other players. He feels better after downing several pints of beer
following the game, but notes darker urine. Urinalysis is posi-
tive for blood. Which of the following pathogenic mechanisms
underlies change in the color of urine?
A Complement lysis
B Intravascular disruption
C Osmotic fragility
D Sinusoidal sickling
E Splenic sequestration
24 In an epidemiologic study of anemias, the findings show
that there is an increased prevalence of anemia in individu-
als of West African ancestry. By hemoglobin electrophoresis,
some individuals within this region have increased hemoglo-
bin S levels. The same regions also have a high prevalence of
an infectious disease. Which of the following infectious agents
is most likely to be endemic in the region where such anemia
shows increased prevalence?
A Borrelia burgdorferi
B Clostridium perfringens
C Cryptococcus neoformans
D Plasmodium falciparum
E Treponema pallidum
F Trypanosoma brucei
 CHAPTER 14 Hematopathology of Red Blood Cells and Bleeding Disorders
25 An infant is born at 34 weeks’ gestation to a 28-year-old
woman, G3, P2. At birth, the infant is observed to be markedly
hydropic and icteric. A cord blood sample is taken, and direct
Coombs test result is positive for the infant’s RBCs. Which of
the following is the most likely mechanism for the findings in
this infant?
A Hemolysis of antibody-coated cells
B Hematopoietic stem cell defect
C Impaired globin synthesis
D Mechanical fragmentation of RBCs
E Oxidative injury to hemoglobin
F Reduced deformability of RBC membranes
26 A 22-year-old woman after returning from a trip to
Africa has experienced febrile episodes over the past 2 weeks.
On physical examination, her temperature is 37.5° C, pulse is
82/min, respirations are 18/min, and blood pressure is 105/65
mm Hg. Laboratory studies show hemoglobin of 10.8 g/dL,
hematocrit of 32.5%, platelet count of 245,700/mm3, and WBC
count of 8320/mm3. The serum haptoglobin level is decreased,
and direct and indirect Coombs test results are negative. The
reticulocyte count is increased. The prothrombin time is 12
seconds, and the partial thromboplastin time is 31 seconds.
She is observed over the next week and found to have tem-
perature spikes to 39.1° C, with shaking chills every 48 hours.
Infection with which of the following organisms is most likely
to cause this patient’s illness?
A Aspergillus niger
B Babesia microti
C Dirofilaria immitis
D Escherichia coli
E Plasmodium vivax
F Wuchereria bancrofti
27 A 33-year-old previously healthy man with persistent
fever and heart murmur is diagnosed with infective endocar-
ditis. He receives a high dosage of a cephalosporin antibiotic
during the next 10 days. He now has increasing fatigue. On
physical examination he has tachycardia and scleral icterus.
Laboratory studies show a hemoglobin level of 7.5 g/dL,
platelet count of 261,000/mm3, and total WBC count of 8300/
mm3. The direct Coombs test is positive. The periperal blood
smear shows reticulocytosis. Which of the following is the
most likely cause for his anemia?
A Dietary nutrient deficiency
B Disseminated intravascular coagulopathy
C Immune-mediated hemolysis
D Infection with parvovirus
E Inherited hemoglobinopathy
F RBC cytoskeletal protein disorder
  
209
28 A 7-year-old child has had worsening headaches and
is obtunded for the past 2 days. Physical examination shows
temperature of 39.5° C, pulse of 103/min, respirations of 18/
min, and blood pressure of 90/55 mm Hg. There is bilateral
papilledema on funduscopic examination. No focal neuro-
logic deficits are noted. Palpation of the abdomen reveals
hepatosplenomegaly. Laboratory findings show hemoglobin,
9.5 g/dL; hematocrit, 28.8%; MCV, 101 μm3; platelet count,
145,000/mm3; WBC count, 6920/mm3; Na+, 146 mmol/L; K+,
5.5 mmol/L; Cl–, 106 mmol/L; CO2, 26 mmol/L; creatinine,
2.3 mg/dL; urea nitrogen, 22 mg/dL; LDH, 1095 U/L; and
amylase, 45 U/L. The peripheral blood smear is shown in the
figure. What infectious agent is most likely to produce these
findings?
A Babesia microti
B Borrelia burgdorferi
C Leishmania donovani
D Plasmodium falciparum
E Trypanosoma brucei
F Wuchereria bancrofti
29 A 54-year-old, previously healthy man has experienced
minor fatigue on exertion for the past 9 months. On physical
examination, there are no remarkable findings. Laboratory
studies show hemoglobin of 11.7 g/dL, hematocrit of 34.8%,
MCV of 73 μm3, platelet count of 315,000/mm3, and WBC
count of 8035/mm3. Which of the following is the most sensi-
tive and cost-effective test that the physician should order to
help to determine the cause of these findings?
A Bone marrow biopsy
B Hemoglobin electrophoresis
C Serum ferritin
D Serum haptoglobin
E Serum iron
F Serum transferrin
210 UNIT II Diseases of Organ Systems
30 A 73-year-old man takes no medications and has had no
prior major illnesses or surgeries. For the past year, he has be-
come increasingly tired and listless. Physical examination shows
that he appears pale but has no hepatosplenomegaly and no de-
formities. CBC shows hemoglobin, 9.7 g/dL; hematocrit, 29.9%;
MCV, 69.7 mm3; RBC count, 4.28 million/mm3; platelet count,
331,000/mm3; and WBC count, 5500/mm3. His peripheral blood
smear is shown in the figure. Which of the following is the most
likely underlying condition causing this patient’s findings?
A Autoimmune hemolytic anemia
B Chronic alcohol abuse
C β-Thalassemia major
D Hemophilia A
E Occult malignancy
F Vitamin B12 deficiency
31 A clinical study is performed using adult patients
­ iagnosed with peptic ulcer disease, chronic blood loss, and
d philic RBCs are difficult to find. A few of the neutrophils show
hypochromic microcytic anemia. Their serum ferritin levels
average 5 to 7 ng/mL. The rate of duodenal iron absorption
in this study group is found to be much higher than in a nor-
mal control group. After treatment with omeprazole and clar-
ithromycin, study group patients have hematocrits of 40% to
42%, MCV of 82 to 85 μm3, and serum ferritin of 30 to 35 ng/
mL. Measured rates of iron absorption in the study group after
therapy are now decreased to the range of the normal controls.
Which of the following substances derived from liver is most
likely to have been decreased in the study group patients be-
fore therapy, and returned to normal after therapy?
A Divalent metal transporter-1 (DMT-1)
B Hemosiderin
C Hepcidin
D HLA-like transmembrane protein
E Transferrin
32 A 39-year-old man has experienced chronic fatigue and
weight loss for the past 3 months. There are no remarkable
findings on physical examination. Laboratory studies show
hemoglobin, 10.0 g/dL; hematocrit, 30.3%; MCV, 91 μm3;
platelet count, 240,000/mm3; WBC count, 7550/mm3; serum
iron 80 μg/dL; total iron-binding capacity, 145 μg/dL; and se-
rum ferritin, 565 ng/mL. Serum erythropoetin levels are low
for the level of Hb and hepcidin levels are elevated. Which of
the following is the most likely diagnosis?
A Anemia of chronic disease
B Aplastic anemia
C Iron deficiency anemia
D Megaloblastic anemia
E Microangiopathic hemolytic anemia
F Thalassemia minor
33 A 45-year-old woman has experienced worsening a­ rthritis
of her hands and feet for the past 15 years. On physical examina-
tion, there are marked deformities of the hands and feet, with ul-
nar deviation of the hands and swan-neck deformities of the fin-
gers. Laboratory studies show an elevated level of rheumatoid
factor. CBC shows hemoglobin, 11.6 g/dL; hematocrit, 34.8%;
MCV, 87 μm3; platelet count, 268,000/mm3; and WBC count,
6800/mm3. There is a normal serum haptoglobin level, serum
iron concentration of 20 μg/dL, total iron-binding capacity of
195 μg/dL, percent saturation of 10.2, and serum ferritin concen-
tration of 317 ng/mL. No fibrin split products are detected. The
reticulocyte concentration is 1.1%. What is the most likely mech-
anism underlying this patient’s hematologic abnormalities?
A Autoantibodies against RBC membranes
B Impaired synthesis of β-globin chains
C Inadequate usage of stored iron
D Mutation in the phosphatidylinositol glycan A
(PIGA) gene
E Sequestration of RBCs in splenic sinusoids
F Space-occupying lesions in the bone marrow
34 A 62-year-old man is taken to the emergency department
in a state of inebriation. He is well known there because this sce-
nario has been repeated many times over 15 years. On physical
examination, he is afebrile. The spleen tip is palpable, and the liv-
er edge is firm. Laboratory studies show hemoglobin of 8.2 g/dL,
hematocrit of 25.1%, MCV of 107 μm3, platelet count of 135,000/
mm3, and WBC count of 3920/mm3. The peripheral blood smear
shows prominent anisocytosis and macrocytosis. Polychromato-
six to seven nuclear lobes. Which of the following is the most
likely explanation of these findings in his peripheral blood cells?
A Diminished nuclear maturation from impaired
DNA synthesis
B Extravascular hemolysis of antibody-coated cells
C Imbalance in synthesis of α-globin and β-globin chains
D Increased susceptibility to lysis by complement
E Reduced deformability of RBC membranes
35 An 83-year-old man complains of worsening malaise
and fatigue over the past 5 months. On physical examination,
he is afebrile and normotensive. The spleen tip is palpable.
A CBC shows hemoglobin, 10.6 g/dL; hematocrit, 29.8%;
MCV, 92 μm3; platelet count, 95,000/mm3; and WBC count,
4900/mm3 with 63% segmented neutrophils, 7% bands, 2%
metamyelocytes, 1% myelocytes, 22% lymphocytes, 5% mono-
cytes, and 3 nucleated RBCs per 100 WBCs. The peripheral
blood smear shows occasional teardrop cells. An examination
of the bone marrow biopsy specimen and smear is most likely
to show which of the following findings?
A Erythroid hyperplasia
B Extensive fibrosis
C Fatty replacement
D Many megaloblasts
E Numerous myeloblasts
 CHAPTER 14 Hematopathology of Red Blood Cells and Bleeding Disorders
36 A clinical study is performed to assess outcomes in pa-
tients who have macrocytic anemias as a result of Vitamin 12
or folate deficiency. A comparison of laboratory testing strate-
gies shows that the best strategy includes testing for serum
homocysteine, methylmalonic acid, vitamin B12 (cobalamin),
and folate. What is the most important reason for ordering
these tests simultaneously?
A Aplastic anemia can result from lack of either nutrient
B Both nutrients are absorbed similarly
C Neurologic injury must be prevented
D Life-threatening thrombocytopenia can occur in both
E Therapy for one deficiency also treats the other
37 A 37-year-old woman has experienced abdominal pain
and intermittent low-volume diarrhea for the past 3 months.
On physical examination, she is afebrile. A stool sample is
positive for occult blood. A colonoscopy is performed, and
biopsy specimens from the terminal ileum and colon show mi-
croscopic findings consistent with Crohn disease. She does not
respond to medical therapy, and part of the colon and termi-
nal ileum are removed. She is transfused with 2 U of packed
RBCs during surgery. Three weeks later, she appears healthy,
but complains of easy fatigability. On investigation, CBC find-
ings show hemoglobin of 10.6 g/dL, hematocrit of 31.6%, RBC
count of 2.69 million/μL, MCV of 118 μm3, platelet count of
378,000/mm3, and WBC count of 9800/mm3. The reticulocyte
count is 0.3%. Which of the following is most likely to produce
these hematologic findings?
A Anemia of chronic disease
B Chronic blood loss
C Hemolytic anemia
D Myelophthisic anemia
E Vitamin B12 deficiency
38 A 28-year-old, previously healthy man has noted
i­ ncreasing fatigue for the past 6 months and formation of bruises
after minimal trauma. Over the past 2 days, he has developed
a cough. On physical examination, his temperature is 38.9° C,
and he has diffuse rales in both lungs. He has no hepatospleno-
megaly and no lymphadenopathy. Laboratory findings in-
clude a sputum culture positive for Streptococcus pneumoniae,
hemoglobin of 7.2 g/dL, hematocrit of 21.7%, platelet count of
23,400/mm3, WBC count of 1310/mm3, prothrombin time of
13 seconds, partial thromboplastin time of 28 seconds, and total
bilirubin of 1 mg/dL. The ANA test result is negative. What is
the most likely explanation of these findings?
A Hematopoietic stem cell defect
B Hemolysis of antibody-coated cells
C Increased susceptibility to lysis by complement
D Metastatic adenocarcinoma to bone marrow
E Secondary hypersplenism
39 In a study of idiopathic aplastic anemia, patients are
found who have premature senescence of hematopoietic stem
cells. Their hematopoietic cells have normal morphology, but
there are fewer cells in myeloid, erythroid, and megakaryo-
cytic cell lines. Which of the following enzymes is most likely
deficient in their marrow stem cells?
A Alkaline phosphatase
B Metalloproteinase
C Pyruvate kinase
D Telomerase
E Tyrosine kinase
211
40 A 44-year-old woman has a 2-week history of multiple
ecchymoses on her extremities after only minor trauma. She
also reports feeling extremely weak. Over the previous 24
hours, she has developed a severe cough productive of yel-
lowish sputum. On physical examination, her temperature is
38.4° C, and she has diffuse crackles on all lung fields. Labora-
tory studies show hemoglobin, 7.2 g/dL; hematocrit, 21.4%;
MCV, 88 μm3; platelet count, 35,000/mm3; and WBC count,
1400/mm3 with 20% segmented neutrophils, 1% bands, 66%
lymphocytes, and 13% monocytes. The reticulocyte count is
0.1%. Which of the following historical findings would be
most useful in determining the cause of her condition?
A Dietary habits
B Exposure to medications
C Family history of anemias
D Menstrual history
E Recent bacterial infection
41 A 77-year-old man has experienced increasing malaise
and a 6-kg weight loss over the past year. He has noted more
severe and constant back pain for the past 3 months. On physi-
cal examination, his temperature is 38.7° C. His prostate is firm
and irregular when palpated on digital rectal examination.
There is no organomegaly. A stool sample is negative for oc-
cult blood. Laboratory studies include a urine culture positive
for Escherichia coli, serum glucose of 70 mg/dL, creatinine of
1.1 mg/dL, total bilirubin of 1 mg/dL, alkaline phosphatase
of 293 U/L, calcium of 10.3 mg/dL, phosphorus of 2.6 mg/dL,
and PSA of 25 ng/mL. CBC shows hemoglobin, 9.1 g/dL; he-
matocrit, 27.3%; MCV, 94 μm3; platelet count, 55,600/mm3; and
WBC count, 3570/mm3 with 18% segmented neutrophils, 7%
bands, 2% metamyelocytes, 1% myelocytes, 61% l­ ymphocytes,
11% monocytes, and 3 nucleated RBCs per 100 WBCs. What is
the most likely diagnosis?
A Anemia of chronic disease
B Aplastic anemia
C Hemolytic anemia
D Megaloblastic anemia
E Myelophthisic anemia
42 A 48-year-old woman has experienced increasing weak-
ness and dyspnea for the past 5 months. On physical examina-
tion, her temperature is 37° C, pulse 100/minute, respiratory
rate 19/min, and blood pressure 115/75 mm Hg. Auscultation
of the lungs reveals bilateral basilar crackles. Muscle strength
diminishes from 5/5 to 4/5 with repetitive movement of her
arms. Her strength returns with administration of an acetyl-
cholinestrase inhibitor. A chest CT scan reveals a 6-cm cir-
cumscribed anterior mediastinal mass. Which of the following
findings is most likely to be present on microscopic examina-
tion of her bone marrow biopsy?
A Erythroid hypoplasia
B Lymphocytosis
C Megakaryocytic hyperplasia
D Metastatic carcinoma
E Myelofibrosis
F Plasmacytosis
212 UNIT II Diseases of Organ Systems
43 Soon after crossing the finish line in a 10-km race, a
31-year-old man collapses. On physical examination, his tem-
perature is 40.1° C, pulse is 101/min, respirations are 22/min,
and blood pressure is 85/50 mm Hg. He is not perspiring, and
his skin shows decreased turgor. Laboratory studies show
Na+, 155 mmol/L; K+, 4.6 mmol/L; Cl−, 106 mmol/L; CO2, 27
mmol/L; glucose, 68 mg/dL; creatinine, 1.8 mg/dL; hemoglo-
bin, 20.1 g/dL; hematocrit, 60.3%; platelet count, 230,400/mm3;
and WBC count, 6830/mm3. What is the most likely diagnosis?
A Erythroleukemia
B Chronic obstructive pulmonary disease
C Diabetes insipidus
D Hemoconcentration
E Paraneoplastic syndrome
F Polycythemia vera
44 A 33-year-old woman, G3, P0, who has had two spon-
taneous abortions, is in the second trimester of her third
pregnancy. An ultrasound at 18 weeks’ gestation revealed
symmetric growth retardation. She gives birth to a stillborn
fetus at 25 weeks, and experiences sudden onset of dyspnea.
A pulmonary ventilation/perfusion scan indicates a high
probability of thromboembolism. Four months later, she
experiences an altered state of consciousness and sudden
loss of movement in the right arm. A cerebral angiogram
shows occlusion of a branch of the left middle cerebral ar-
tery. Laboratory findings show hemoglobin, 13.4 g/dL; he-
matocrit, 40.3%; MCV, 91 μm3; platelet count, 124,000/mm3;
WBC count, 5530/mm3; prothrombin time, 13 seconds; par-
tial thromboplastin time, 46 seconds; positive anticardiolip-
in antibody; positive serologic test result for syphilis; and
negative ANA. Which of the following best explains these
findings?
A Antiphospholipid syndrome
B Myeloproliferative disorder
C Thrombophlebitis
D Treponema pallidum infection
E Trousseau syndrome
F Von Willebrand disease
45 A 23-year-old woman in her 25th week of pregnancy has
felt no fetal movement for the past 3 days. Three weeks later,
she still has not given birth and suddenly develops dyspnea
with cyanosis. On physical examination, her temperature is 37°
C, pulse is 106/min, respirations are 23/min, and blood pres-
sure is 80/40 mm Hg. She has large ecchymoses over the skin
of her entire body. A stool sample is positive for occult blood.
Laboratory studies show an elevated prothrombin time and
partial thromboplastin time. The platelet count is decreased,
plasma fibrinogen is markedly decreased, and fibrin split prod-
ucts are detected. A blood culture is negative. Which of the fol-
lowing is the most likely cause of her bleeding diathesis?
A Consumption of coagulation factors
B Defects in platelet aggregation
C Increased vascular fragility
D Reduced production of platelets
E Toxic injury to the endothelium
  
46 A 30-year-old man has had pain and burning on urination
for the past week. On physical examination, he is febrile and has
a pulse of 92/min, respirations of 18/min, and blood pressure of
80/45 mm Hg. Digital rectal examination indicates that he has
an enlarged, tender prostate. There is costovertebral angle ten-
derness on the right. Scattered ecchymoses are present over the
trunk and extremities. Laboratory studies show a blood culture
positive for Klebsiella pneumoniae. The appearance of the RBCs
in a peripheral blood smear is shown in the figure. Which of the
following hematologic disorders is he most likely to have?
A Autoimmune hemolytic anemia
B Hereditary spherocytosis
C Iron deficiency anemia
D Megaloblastic anemia
E Microangiopathic hemolytic anemia
47 A 37-year-old woman has noted an excessively heavy
menstrual flow each of the past 6 months. She also has noticed
increasing numbers of pinpoint hemorrhages on her lower ex-
tremities in the past month. Physical examination shows no or-
ganomegaly or lymphadenopathy. CBC shows hemoglobin of
14.2 g/dL, hematocrit of 42.5%, MCV of 91 μm3, platelet count
of 15,000/mm3, and WBC count of 6950/mm3. On admission
to the hospital, she has melena and after a transfusion of plate-
lets, her platelet count does not increase. Which of the follow-
ing describes the most likely basis for her bleeding tendency?
A Abnormal production of platelets by
megakaryocytes
B Defective platelet-endothelial interactions
C Destruction of antibody-coated platelets by the spleen
D Excessive loss of platelets in menstrual blood
E Suppression of pluripotent stem cell division
48 A 9-year-old boy has developed prominent bruises on
his extremities over the past week. On physical examina-
tion, he has ecchymoses and petechiae on his arms and legs.
Laboratory studies show hemoglobin, 13.8 g/dL; hematocrit,
41.9%; MCV, 93 μm3; platelet count, 11,300/mm3; and WBC
count, 7720/mm3. He had respiratory syncytial virus pneumo-
nia 3 weeks ago. His condition improves with corticosteroid
therapy. Which of the following abnormalities is most likely to
cause his hemorrhagic diathesis?
A Antiplatelet antibodies
B Bone marrow aplasia
C Glycoprotein IIb/IIIa dysfunction
D Vitamin C deficiency
E Von Willebrand factor metalloproteinase deficiency
 CHAPTER 14 Hematopathology of Red Blood Cells and Bleeding Disorders
49 A 21-year-old woman known to have a protein C defi-
ciency develops recurrent pulmonary thromboembolism and
is placed on anticoagulant therapy. Two weeks after initiation
of this therapy, she has a sudden change in mental status and
experiences difficulty speaking and swallowing. A cerebral
angiogram shows a left middle cerebral artery occlusion. Lab-
oratory studies show hemoglobin of 13 g/dL, platelet count of
65,400/mm3, WBC count of 5924/mm3, prothrombin time of
12 seconds, and partial thromboplastin time of 51 seconds. The
anticoagulant therapy is discontinued. Which of the following
pharmacologic agents used as an anticoagulant in this patient
is most likely to have caused these findings?
A Acetylsalicylic acid (aspirin)
B Heparin
C Tissue plasminogen activator
D Urokinase
E Warfarin
50 A 56-year-old woman suffers the sudden onset of head-
ache and photophobia, and her condition worsens for the next 2
days. On physical examination, she has a temperature of 38° C
and is disoriented. CBC shows hemoglobin of 11.2 g/dL, he-
matocrit of 33.7%, MCV of 94 μm3, platelet count of 32,000/
mm3, and WBC count of 9900/mm3. The peripheral blood
smear shows schistocytes. The serum urea nitrogen level is 38
mg/dL, and the creatinine level is 3.9 mg/dL. Which of the
following is the most likely diagnosis?
A Autoimmune hemolytic anemia
B β-Thalassemia major
C Disseminated intravascular coagulation
D Idiopathic thrombocytopenic purpura
E Paroxysmal nocturnal hemoglobinuria
F Thrombotic thrombocytopenic purpura
51 A 44-year-old woman has experienced malaise with
nausea and vomiting for 3 months. On physical examination,
she has scleral icterus and a yellowish hue to her skin. She has
difficulty remembering three objects after 3 minutes. There
are no neurologic deficits. Laboratory studies show a positive
serologic test result for hepatitis C, a serum ALT of 310 U/L,
AST of 269 U/L, total bilirubin of 7.6 mg/dL, direct bilirubin
of 5.8 mg/dL, alkaline phosphatase of 75 U/L, and ammonia
of 55 μmol/L. An abnormal result of which of the following
laboratory studies of hemostatic function is most likely to be
reported?
A Fibrin split products
B Immunoassay for plasma von Willebrand factor
C Platelet aggregation
D Platelet count
E Prothrombin time
52 A 23-year-old woman has a history of easy bruising.
Physical examination shows multiple bruises ranging in color
from red to blue to purple on her arms and legs. There is no or-
ganomegaly, and no deformities are noted. Laboratory studies
show hemoglobin, 9.5 g/dL; hematocrit, 28.2%; platelet count,
229,300/mm3; WBC count, 7185/mm3; prothrombin time, 12
seconds; and partial thromboplastin time, 38 seconds. A 1:1
dilution of the patient’s plasma with normal pooled plasma
corrects the partial thromboplastin time. Ristocetin-dependent
platelet aggregation in patient plasma is markedly reduced.
Factor VIII activity is 30% (reference range 50% to 150%).
213
Which of the following is the most likely potential consequence
of this disease?
A Bone marrow failure from aplasia
B Excessive bleeding after oral surgery
C Increasing difficulty with joint mobility
D Myeloproliferative disorder
E Recurrent deep venous thrombosis
53 A 42-year-old woman has had nosebleeds, easy bruising,
and increased bleeding with her menstrual periods for the past
4 months. On physical examination, her temperature is 37° C,
pulse is 88/min, and blood pressure is 90/60 mm Hg. She has
scattered petechiae over the distal extremities. There is no or-
ganomegaly. Laboratory studies show hemoglobin of 12.3 g/
dL, hematocrit of 37%, platelet count of 21,500/mm3, and WBC
count of 7370/mm3. A bone marrow biopsy specimen shows
a marked increase in megakaryocytes. The prothrombin and
partial thromboplastin times are within the reference range.
What is the most likely diagnosis?
A Disseminated intravascular coagulation
B Hemophilia B
C Immune thrombocytopenic purpura
D Metastatic breast carcinoma
E Thrombotic thrombocytopenic purpura
F Vitamin K deficiency
G Von Willebrand disease
54 A clinical study is performed involving adult patients
diagnosed with microangiopathic hemolytic anemia. A sub-
group of patients who had fever or diarrhea preceding the
initial diagnosis of anemia were excluded. The patients had
schistocytes present on peripheral blood smears. Some of these
patients were found to have a deficiency of a metalloprotein-
ase known as ADAMTS13. Which of the following conditions
were the patients with this deficiency most likely to have?
A Disseminated intravascular coagulation (DIC)
B Hemolytic-uremic syndrome (HUS)
C Heparin-induced thrombocytopenia (HIT)
D Idiopathic thrombocytopenic purpura (ITP)
E Thrombotic thrombocytopenic purpura (TTP)
55 A 45-year-old woman has had episodes of blurred vi-
sion and headaches for the past 6 months. She has had wors-
ening confusion with paresthesias over the past 3 days. On
physical examination, she has a temperature of 39.6° C, pulse
of 100/min, respiratory rate of 20/min, and blood pressure
of 80/50 mm Hg. Petechial hemorrhages are noted over her
trunk and extremities. Laboratory findings include hemoglo-
bin, 10.9 g/dL; hematocrit, 34%; MCV, 96 μm3; platelet count,
28,000/mm3; and WBC count, 8500/mm3. Fragmented RBCs
are noted on her peripheral blood smear. Blood urea nitrogen
is 40 mg/dL, and serum creatinine is 3.1 mg/dL. Which of the
following is the most likely underlying cause for her findings?
A Circulating toxin that injures capillary endothelium
B Decreased factor VIII activity
C Defective ADP-induced platelet aggregation
D Formation of autoantibodies to platelet glycopro-
teins IIb/IIIa and Ib-IX
E Inappropriate release of thromboplastic substances
into blood
F Presence of antibodies against ADAMTS13
metalloproteinase
214 UNIT II Diseases of Organ Systems
56 A 12-year-old boy has had worsening problems with joint
mobility involving his arms and legs, particularly his knees and
ankles, for the past 6 years. He has been receiving therapy for
this condition. His grandfather had a similar condition and died
at age 25 years. On physical examination, he has no visible pe-
techiae or areas of purpura. Laboratory studies show that pro-
thrombin time is 12 seconds, and partial thromboplastin time
is 52 seconds. After addition of an equivalent aliquot of normal
plasma, the partial thromboplastin time is 30 seconds. Hemo-
globin is 12.9 g/dL, platelet count is 238,500/mm3, and WBC
count is 6620/mm3. His platelet function studies are normal.
What is the most likely inheritance pattern for his condition?
A Autosomal dominant
B Autosomal recessive
C Confined placental mosaicism
D Germline mutation
E X-linked recessive
57 An 11-year-old child has a history of easy bruising. At
age 9 years, he experienced hemorrhaging around the phar-
ynx that produced acute airway obstruction. Family history
indicates that other male relatives have similar bleeding prob-
lems. Laboratory studies show hemoglobin, 13.1 g/dL; hema-
tocrit, 39.2%; platelet count, 228,000/mm3; WBC count, 5950/
mm3; prothrombin time, 13 seconds; and partial thromboplas-
tin time, 52 seconds. A 1:1 dilution of the patient’s plasma with
normal pooled plasma corrects the partial thromboplastin
time. Which of the following manifestations of this illness is
most likely to ensue without therapy?
A Conjunctival petechiae
B Hemarthroses
C Hemolysis
D Hemochromatosis
E Splenomegaly
58 A 15-year-old girl has a history of easy bruising and
hemorrhages. Since menarche at the age of 13 years, she has
had menometrorrhagia. On physical examination, she dis-
plays joint deformity and has decreased mobility of the an-
kles, knees, and wrists. Laboratory studies show hemoglobin,
11.8 g/dL; hematocrit, 35.1%; platelet count, 267,000/mm3;
WBC count, 5960/mm3; prothrombin time, 13 seconds; and
partial thromboplastin time, 60 seconds. A 1:1 dilution of the
patient’s plasma with normal pooled plasma corrects the par-
tial thromboplastin time. Which of the following is the most
likely diagnosis?
A Antiphospholipid syndrome
B Hemophilia B
C Idiopathic thrombocytopenic purpura
D Thrombotic thrombocytopenic purpura
E Von Willebrand disease
59 A 16-year-old girl has had frequent nosebleeds since
childhood. Her gums bleed easily, even with routine tooth
brushing. She has experienced menorrhagia since menarche
at age 13 years. On physical examination, there are no ab-
normal findings. Laboratory studies show hemoglobin,
14.1 g/dL; hematocrit, 42.5%; MCV, 90 μm3; platelet count,
277,400/mm3; and WBC count, 5920/mm3. Her platelets fail
to aggregate in response to ADP, collagen, epinephrine, and
thrombin. The ristocetin agglutination test result is normal.
There is a deficiency of glycoprotein IIb/IIIa. Prothrombin
time is 12 seconds, and partial thromboplastin time is 28 seconds.
What is the most likely diagnosis?
A Disseminated intravascular coagulation
B Glanzmann thrombasthenia
C Immune thrombocytopenic purpura
D Vitamin C deficiency
E Von Willebrand disease
60 A 25-year-old man involved in a motorcycle accident
incurs a laceration to his thigh. The bleeding is stabilized en
route to the hospital, but on arrival he is noted to have or-
thostatic hypotension and his hematocrit is 21%. He receives
2 units of PRBCs. As the first unit is nearly finished transfus-
ing, he becomes febrile and hypotensive. Urine output ceases.
The serum above the clot in a red top phlebotomy tube is pink.
Which of the following complications of transfusion has most
likely occurred in this man?
A Donor antibodies were directed against his
granulocytes
B Donor blood was contaminated with hepatitis C
virus
C Fluid overload led to congestive heart failure
D Mislabeled specimens were processed in the
laboratory
E Foreign T lymphocytes attacked his tissues
61 A 72-year-old woman undergoes laparotomy for rup-
tured diverticulitis. A day later her WBC count is elevated
and her blood pressure is 85/45 mm Hg. Her peripheral blood
smear shows schistocytes. She receives 5 units of fresh frozen
plasma. As the 5th unit is being transfused, she develops sud-
den severe dyspnea and begins coughing up large quantities
of frothy sputum. A chest radiograph shows bilateral pulmo-
nary edema. She is most likely to have developed a transfu-
sion reaction to which of the following components of the do-
nor blood product?
A Albumin
B Fibrinogen
C Granulocytes
D Platelets
E Red blood cells
62 A study of transfusion reactions reveals that some
­ atients experienced an increase in body temperature that
p
was greater than 1°C, accompanied by chills and hypoten-
sion. Blood cultures are positive for bacterial organisms.
These patients respond to antibiotic therapy. Which of the
following types of blood products did they most likely
receive?
A Cryoprecipitate
B Fresh frozen plasma
C Granulocytes
D Platelets
E Red blood cells