56.

Which of the following viruses is implicated as a possible cause of acquired

prolonged aplastic anemia?
A. Rubella virus
B. Measles virus
C. Cytomegalovirus
D. Herpes virus
E. Parvovirus B19

57. Which of the following antibacterial agents is implicated as a possible cause

of acquired aplastic anemia?
A. Ampicillin
B. Trimethoprim-sulfamethoxazole
C. Cefotaxime
D. Gentamycin
E. Azithromycin

58. Which of the following findings is a criterion of severe aplastic anemia?

A. Absolute neutrophil count 600/mm3
B. Platelet count 18,000/mm3
C. Reticulocyte count 1.5 %
D. Bone marrow biopsy cellularity 33%
E. Hemoglobin level 6.0 gm/dl

59. Cases of Aplastic anemia should be assessed for paroxysmal nocturnal

hemoglobinuria. The MOST sensitive test is
A. direct antiglobulin test
B. hemoglobin F level
C. erythrocyte CD55 and CD59
D. haptoglobin
E. urine for hemosiderin

60. What is the MOST common chromosomal abnormality found within the
marrow of patients with myelodysplastic syndrome?
A. Monosomy 7
B. Monosomy 8
C. Trisomy 11
D. Trisomy 13
E. Trisomy 21
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61. Which of the following lab findings suggest polycythemia due to heart or
lung disease?
A. Normal red cell mass with low plasma volume
B. Elevated red cell mass with high carboxyhemoglobin
C. Elevated red cell mass with low arterial oxygen
D. Normal red cell mass with abnormal hemoglobin study
E. Elevated red cell mass with low erythropoietin

62. Which of the following is a major WHO criterion for diagnosis of

Polycythemia Vera?
A. Red cell mass 20% above mean normal predicted value
B. Bone marrow trilineage myeloproliferation
C. Subnormal serum erythropoietin level
D. Endogenous erythroid colony growth
E. Presence of JAK2 or similar mutation

63. What is the usual physical finding in polycythemia?

A. Hepatosplenomegaly
B. Skin ecchymosis
C. Pruritus marks
D. Hypertension
E. lymphadenopathy

64. What is the MOST convenient initial treatment of polycythemia?

A. Phlebotomy
B. Aspirin
C. Hydroxyurea
D. Interferon-gamma
E. Iron

65. Among infants less than 4 months of age, which of the following is an
indication of blood transfusion?
A. Hemoglobin less than 14.0 gm/dl in patient with severe pulmonary
disease
B. Hemoglobin less than 10.0 g/dl in patient with moderate pulmonary
disease
C. Hemoglobin less than 14.0 g/dl in patients with severe cardiac disease
D. Hemoglobin less than 11.0 g/dl preoperatively and during major surgery
476
 E. Hemoglobin less than 10.0 g/dl postoperatively

66. What is the key reason that the nadir hemoglobin values of premature
infants are lower than those of term infants?
A. Bleeding is more common among premature infants
B. Bone marrow is relatively lazy in premature infants
C. Rate of hemolysis in premature infants is greater than term
D. Diminished plasma erythropoietin in response to anemia
E. Fetal hemoglobin replacement is slow among premature infants

67. According to the guidelines of pediatric platelet transfusion, patients with

marrow failure and hemorrhagic risk factors (infection, organ failure, and
clotting abnormalities) should have their platelets count maintained above
A. 80,000/mm3
B. 60,000/mm3
C. 40,000/mm3
D. 20,000/mm3
E. 10,000/mm3

68. A 1-month-old infant with sepsis on aggressive antibiotic therapy, while he is

clinically unstable requires a platelet count to be maintained above
A. 100,000/mm3
B. 70,000/mm3
C. 50,000/mm3
D. 30,000/mm3
E. 10,000/mm3

69. In patients with inherited platelet disorders, platelet transfusions are

justified only for overt bleeding and high risk of bleeding. This is because
A. the risk of bleeding is less than acquired platelet disorders
B. no response to platelet transfusions
C. life threatening bleeding is seldom in these disorders
D. possible association with transfusion reaction
E. repeated transfusions lead to refractoriness

70. Granulocyte transfusion for a 3-day-old newborn is indicated with a

threshold of neutrophil count below?
A. 1,000/mm3
477
 B. 1,500/mm3
C. 2,000/mm3
D. 2,500/mm3
E. 3,000/mm3

71. Which of the following factors reduces the level of von Willebrand factor?
A. Stress
B. Infections
C. Hypothyroidism
D. Exercise
E. Pregnancy

72. Which of the following types of von Willebrand disease is misdiagnosed as

hemophilia due to low factor VIII level?
A. Type 1C
B. Type 2A
C. Type 2B
D. Type 2M
E. Type 2N

73. Which type of von Willebrand disease presents with thrombocytopenia?

A. Type 1C
B. Type 2A
C. Type 2B
D. Type 2M
E. Type 2N

74.Which of the following subtypes of von Willebrand disease is likely to benefit

from Desmopressin?
A. Type 1
B. Type 1C
C. Type 2A
D. Type 2B
E. Type 3

75. Which of the following conditions causes thrombocytopenia through

impaired platelets production?
A. Kasabach-Merritt syndrome
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 B. Hypersplenism
C. Hypothermia
D. Infection-induced thrombocytopenia
E. Osteopetrosis

76. A 3-year-old boy presents with sudden onset of generalized petechiae and
purpura for the last two days, he is otherwise healthy and playful. Parents deny
any previous similar episodes and family illnesses. His general examination
showed active boy with normal vitals and no abnormality in general exam apart
from these skin lesions. His heart exam is normal, chest note is normal and
abdominal exam fails to identify organ enlargement.
Of the following, the MOST likely diagnosis is
A. aplastic anemia
B. immune thrombocytopenia
C. acute leukemia
D. Glanzmann thrombasthenia
E. von Willebrand disease

77. Which of the following lab tests results is worrisome in immune

thrombocytopenia and should raise the suspicion of another diagnosis?
A. A platelet count of 1.000 /mm3
B. A WBCs count of 2.500 /mm3
C. A hemoglobin count of 8.0 gm/dl
D. A bone marrow examination showing increase number of
megakaryocytes
E. A negative Coombs test

78. Autoimmune screen, in the context of immune thrombocytopenia, is

required in which of the following clinical conditions?
A. Five-year-old girl with long history of skin and mucosal bleeding lasting
more than one year
B. Acute history of severe profound epistaxis, heralding possible need for
blood transfusion
C. Acute presentation of intracranial hemorrhage in a background of two
weeks skin bleeding that wasn’t without a prior problem
D. Periorbital bleeding suggesting basal skull fracture after road traffic
accident in a newly diagnosed immune thrombocytopenia with one
month of the accident
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 E. An adolescent girl presented with severe menorrhagia and pallor, with a
background of few weeks skin ecchymosis with reluctance for medical
counseling for social reasons

79. A 6-year-old girl presents with recurrent skin ecchymosis and petechial rash
over the abdomen and lower limbs for the last few weeks. Her past medical
history is negligible apart from frequent neonatal exchange transfusion for
severe Rh incompatibility. Her regional exam shows a clear chest note, normal
heart sounds, and soft palpable spleen of 5 cm BCM with no hepatomegaly and
no palpable masses. His CBC film shows isolated thrombocytopenia, normal
other indices and normal film.
Of the following, the MOST likely diagnosis is
A. acute lymphoblastic leukemia
B. portal vein thrombosis
C. immune thrombocytopenia
D. chronic liver disease
E. aplastic anemia

80. Autoimmune thrombocytopenia may be the initial manifestation of which of

the following malignancies?
A. Neuroblastoma
B. Lymphoma
C. Wilms’ tumor
D. Rhabdomyosarcoma
E. Ewing’s sarcoma

81. A 3-year-old boy presents with skin bleeding (ecchymosis and petechial
rash) over the lower and upper limbs for two-days, no other site of bleeding and
no constitutional symptoms. His mother denies any similar illness in his history
and in the family. Examination of this child was normal. CBC film shows isolated
thrombocytopenia (33.000/mm3).
Of the following, the MOST appropriate initial treatment is
A. observation
B. steroid
C. IVIG
D. rituximab
E. thrombopoietin receptor agonist

480
82. What is the BEST treatment option for a newly diagnosed immune
thrombocytopenia in a 6-year-old naughty child, diagnosed as ADHD in his early
childhood?
A. Observation
B. Splenectomy
C. IVIG
D. Rituximab
E. Thrombopoietin receptor agonist

83. What is the BEST curative option for a chronic immune thrombocytopenia in
a 10-year-old male child, with recurrent epistaxis and gum bleeding that impairs
his daily active life style?
A. Observation
B. Splenectomy
C. IVIG
D. Rituximab
E. Thrombopoietin receptor agonist

84. Which of the following is a TRUE fact regarding therapy of idiopathic

immune thrombocytopenia?
A. The majority of patient have moderate to severe symptoms of bleeding
B. Early therapy does not prevent intracranial hemorrhage
C. Initiating early therapy affect the outcome of the disease
D. Antiplatelets antibodies bind to autologous rather than transfused
platelets
E. Aggressive way of management is preferable so as to control bleeding

85. Splenectomy in Immune thrombocytopenia (ITP) is considered in which of

the following conditions?
A. A two-year old boy with newly diagnosed ITP whose bleeding symptoms
failed to be ameliorated with steroids and IVIG
B. A ten-year old girl with chronic ITP with recurrent symptoms of skin
bleeding that is diffuse, not responding to steroids, rituximab and other
medical therapy.
C. A six-year old boy with acute ITP developed intracranial hemorrhage
from a road traffic accident who is hemodynamically stable and his
bleeding is controlled with IVIG and steroids

481
 D. A thirteen-year old girl with chronic ITP and severe vaginal bleeding that
necessitated blood transfusion and failed to respond to steroids, IVIG,
rituximab and contraceptive therapy.
E. A five-year old boy with acute ITP on initial therapy with steroid and
presented with severe epistaxis and consequent anemia declared the
need for blood transfusion

86. Passing into the chronic phase of the disease, a patient with immune
thrombocytopenia (ITP) should be carefully evaluated to exclude
A. aplastic anemia
B. acute leukemia
C. HIV infection
D. non-hodgkin lymphoma
E. medical child abuse

87. Thrombotic thrombocytopenic purpura is a rare thrombotic

microangiopathy characterized by the pentad of
A. Fever, microangiopathic hemolytic anemia, thrombocytopenia,
abnormal renal function, and central nervous system changes
B. Pneumonia, microangiopathic hemolytic anemia, thrombocytosis,
abnormal renal function, and central nervous system changes
C. Fever, autoimmune hemolytic anemia, thrombocytopenia, abnormal
liver function, and central nervous system changes
D. Fever, autoimmune hemolytic anemia, thrombocytosis, abnormal renal
function, and central nervous system changes
E. Pneumonia, autoimmune hemolytic anemia, thrombocytosis, abnormal
liver function, and central nervous system changes

88. A 14-year-old boy presents with 3-weeks history of fever, infrequent

vomiting and irritability, followed by weakness in both lower limbs then
progressed to pallor and diffuse petechial rash of the skin, trunk, and lower
limbs. He was treated initially as nonspecific infection with injectable
antibiotics, but seems fruitless. Regrettably, the last few days witnessed
episodes of abnormal movement and disturbed vision. His general examination
showed a semiconscious blind adolescent boy with aggressive behavior, having
pallor, diffuse skin bleeding, without any edema or lymph nodes enlargement.
His meningeal signs were negative and regional exam ENT, chest and abdomen
were normal. His neurological exam showed only a lower limb weakness of
482
grade 3 with diminished reflexes. His CBC showed abnormal RBCs, with
schistocytes, spherocytes, helmet cells, and an elevated reticulocyte count in
association with thrombocytopenia. Blood urea nitrogen and creatinine are
slightly elevated.
Of the followings, the MOST likely diagnosis is
A. hemolytic uremic syndrome
B. thrombotic thrombocytopenic purpura
C. acute leukemia
D. aplastic anemia
E. meningococcemia

89. What is the MOST appropriate effective initial management of acquired

thrombotic thrombocytopenic purpura?
A. Steroids
B. Splenectomy
C. Rituximab
D. IVIG
E. Plasmapheresis

90. A 1-month-old female presented with diffuse skin ecchymosis and petechial
rash since early days of life, she was noticed to have occasional blood spits from
the mouth. No significant antenatal, neonatal, and family history. Initial CBC
shows thrombocytopenia with normal other indices. Other workup tests were
normal. BMA shows normal hematopoietic elements with frank absence of
megakaryocytes.
Of the following, the MOST likely diagnosis is
A. Fanconi anemia
B. congenital dyserythropoietic anemia
C. congenital cytomegalovirus infection
D. congenital leukemia
E. congenital amegakaryocytic thrombocytopenia

91. Which of the following conditions has been linked with Thrombocytopenia-
absent radius (TAR)?
A. Cow’s milk intolerance
B. Diabetes Mellitus
C. Congestive heart failure
D. Chronic renal failure
483
 E. Bronchiectasis

92. A mother of a 3-month-old girl consulted the pediatric clinic for a concern of
accidental discovery of thrombocytopenia during checkup for pallor, which later
labeled to be physiological anemia. She denied any clinical symptoms of
bleeding in her daughter, further workup failed to reveal any abnormality in the
girl, physical examination was completely normal. On further inquiry of the
mother who has sensorineural deafness since early life, she reported that she
had mild to moderate thrombocytopenia during early childhood that persisted
to adulthood with no significant bleeding. Medical archives of both of them
showed platelets count of 25,000 – 50,000 /mm3, sometimes accompanied by
neutrophil inclusion bodies, with normal other indices.
Of the following, the MOST likely diagnosis is
A. thrombocytopenia-absent radius
B. MYH9-related thrombocytopenia
C. congenital aplastic anemia
D. Wiskott-Aldrich syndrome
E. congenital leukemia

93. Which of the following is considered as diagnostic of splenic hypofunction?

A. Target cells
B. Decreased osmotic fragility
C. Heinz bodies
D. Poikilocytosis
E. Pitted erythrocytes

94. Banti syndrome (congestive splenomegaly) is seen in

A. acute myeloid leukemia
B. amyloidosis
C. juvenile idiopathic arthritis
D. alpha1-antitrypsin deficiency
E. Niemann-Pick disease

95. Which of the following abnormalities constitute Ivemark syndrome?

A. Congenital heart defects, renal anomalies, lung hypoplasia, asplenia and
levocardia
B. Congenital heart defects, dextrocardia, bilateral trilobed lungs, asplenia
and heterotopic abdominal organs
484
 C. Cyanotic heart defect, skeletal anomalies, retinal detachment, brain cyst
and gastroschises
D. Congenital renal anomalies, liver cysts, bowel atresia, omphalocele and
congenital abnormalities of the lower limbs
E. Congenital renal anomalies, multiple brain cysts, imperforated anus,
prune belly syndrome and lung cysts

96. What are the characteristic RBC changes in peripheral blood smear of
patients with splenic hypofunction?
A. Howell-Jolly bodies
B. Basophilic stippling
C. Pappenheimer bodies
D. Cabot rings
E. Hemoglobin crystals

97. What is the MOST common pathogen implicated in the etiology of

lymphangitis?
A. Group A streptococci
B. Escherichia coli
C. Pseudomonas aeruginosa
D. Clostridium difficile
E. Proteus species

98. Regardless of the presence or absence of systemic symptoms or other

abnormal physical findings, which of the following properties should always
raise the question of malignancy in a lymph node?
A. Axillary in site
B. Firm and fixed
C. Matted
D. Red overlying skin
E. Tender

99. Which of the following features signifies adenopathy caused by bacteria

rather than other infectious agents?
A. Atypical anatomic areas
B. A draining sinus
C. Lack of prior pyogenic infection
D. A short course
485
 E. Unusual clues in the history

100. Which of the following is an unusual site of tuberculous lymphadenopathy?

A. Hilar
B. Supraclavicular
C. Abdominal
D. Cervical
E. Inguinal

101. Which of the following viruses has been implicated as an association with
Castleman disease?
A. Measles virus
B. Human herpes virus 8
C. Epstein-Barr virus
D. Parvovirus B19
E. Cytomegalovirus

102. TAFRO syndrome stands for

A. Tetany, Anasarca, Facial nerve paralysis, Rhinitis, and Otitis media
B. Typhlitis, Allergy, Fluid retention, Rheumatological problems, and
Organomegaly
C. Thrombocytopenia, Alopecia, Facial nerve paralysis, Rhinitis, and Otitis
media
D. Thrombocytopenia, Anasarca, Fever, Reticulum fibrosis, and
Organomegaly
E. Tetany, Allergy, Fluid retention, Fever, Reticulum fibrosis, and Otalgia

103. POEMS syndrome stands for

A. Polyneuropathy, organomegaly, endocrinopathy, M-proteins, and skin
lesions
B. Polyuria, organomegaly, endocarditis, Myasthenia, and skin lesions
C. Parotid swelling, otitis externa, endocrinopathy, M-proteins and Serositis
D. Polyneuropathy, orchitis, endocrinopathy, Myasthenia, and Serositis
E. Polyuria, organomegaly, edema, M-proteins and skin lesions

486
Chapter 20
Diseases of the Blood
Answers
HASANEIN H. GHALI
1.(D) Erythrocytes in the fetus are larger than in adults, and at 22-23 wk
gestationthe mean corpuscular volume can be as high as 135 femtoliters (fL).
Similarly, the mean corpuscular hemoglobin is very high at 22-23wk and falls
relatively linearly with advancing gestation. In contrast, the mean corpuscular
hemoglobin concentration is constantthroughout gestation at 34 ±1 g/dL.
2.(D) The minor adult hemoglobincomponent, HbA2 , contains delta (δ) chains
and has the structure α2 δ2 . Atbirth, <1.0% of HbA 2 is detected, but by 12 mo
of age the normal level is 2.0–3.4%. Throughout life, the normal ratio of HbA to
HbA2 is about 30 : 1.
3.(A) The normal adult level of HbA2 (2.0–3.4%) is seldom altered. Levels of
HbA2>3.4% are found in most persons with the β-thalassemia trait and in those
with megaloblastic anemias secondary to vitamin B12 and folic acid deficiency.
Decreased HbA2 levels are found in those with iron-deficiency anemia and α-
thalassemia.
4.(C) Microcytes are seen in Iron deficiency, thalassemias, Lead toxicity, and
anemia of chronic disease. Macrocytes are seen in newborns, vitamin B12 or
folate deficiency, Diamond-Blackfan anemia, Fanconi anemia, aplastic anemia,
liver disease, Down syndrome, and hypothyroidism.
5.(D) Basophil stippling are seen in thalassemia, lead intoxication, and
myelodysplasia.
6.(A) Diamond-Blackfan anemia (DBA) is a rare, congenital bone marrow failure
syndrome that usually becomes symptomatic in early infancy. More than 90% of
cases are recognized in the 1st yr of life. The disorder is characterized by
anemia, usually normochromic and macrocytic; reticulocytopenia; and
insufficient or absent red blood cell (RBC) precursors in an otherwise
normallycellular bone marrow. Up to 50% of affected individuals have
additional, extrahematopoietic anomalies.
7.(B) Corticosteroids are a mainstay of therapy, and approximately 80% of
patients initially respond. Because corticosteroids impair linear growth as well
asphysical and neurocognitive development, many hematologists maintain
487
infantson chronic transfusion therapy and delay the start of steroids until after
age 1 yr.
8.(A) The temporary suppression of erythropoiesis results in reticulocytopenia
and moderate to severe normocytic anemia. Some degree of neutropenia
occurs in up to 20% of cases. Platelet numbers are normal or elevated.
9.(D) Soluble transferring receptor (sTfR) is a diagnostic test used to distinguish
ACD from iron-deficiency anemia (IDA); sTfR levels are high in IDA and normal in
ACD.
10.(A) Congenital dyserythropoietic anemia type I CDA I may be diagnosed at
any age, most cases are recognized during childhood or adolescence. CDA I is
rarely diagnosed in utero. In addition to anemia related symptoms, other
findings often include splenomegaly, jaundice, and hepatomegaly. Hemoglobin
concentrations generally range between 7 and 11 g/dL. The anemia is usually
macrocytic (mean corpuscular volume: 100-120 fL), but normocytic indices may
be seen during childhood. Anisopoikilocytosis is appreciated on the peripheral
blood smear. In some cases, normoblasts and basophilic stippling of RBCs may
be seen. The bone marrow aspirate shows binucleated and, more rarely,
multinucleated polychromatophilic erythroblasts are also appreciated.
Electron microscopy is the gold standard for diagnosis, revealing erythroblasts
with a characteristic “Swiss cheese” heterochromatin pattern.
11.(D) In the full-term infant, physiologic anemia requires no therapy beyond
ensuring that the infant’s diet contains essential nutrients for normal
hematopoiesis.
12.(D) Human breast milk, infant formulas, and pasteurized cow’s milk provide
adequate amounts of folic acid. Goat’s milk is folate deficient, and
supplementation must be given when it is the child’s main food.
13.(A) Certain anticonvulsant drugs (e.g., phenytoin, primidone, phenobarbital)
can impair folic acid absorption, and many patients treatedwith these drugs
have low serum levels. Frank megaloblastic anemia is rare and readily responds
to folic acid therapy, even when administrationof the offending drug is
continued.
14.(B) Normal serum folic acid levels are 5-20 ng/mL; with deficiency, levels are
<3 ng/mL.
15.(C) Folic acid therapy (0.5-1.0 mg/day) should be continued for 3-4 wk until a
definite hematologic response has occurred. Maintenance therapy with a
multivitamin (containing 0.2 mgof folate) is adequate.
16.(A) Vitamin B12 deficiency in infants is most often nutritional, resulting from
low Cbl levels in the breast milk of B12-deficient mothers. Associated
488
megaloblastic anemia often appears during the 1st yr of life. Maternalm
deficiency may be caused by pernicious anemia or gastrointestinal disorders
such as Helicobacter pylori infection, celiac disease, Crohn disease, or
pancreatic insufficiency. Previous gastric bypass surgery, treatment with proton
pump inhibitors, or inadequate intake from a strict unsupplemented vegetarian
diet has also been implicated.
17.(C) Imerslund-Grasbeck syndrome is a rare, recessively inherited pediatric
disorder resulting in selective vitamin B12 malabsorption in the ileum and
consequent vitamin B12 deficiency. It usually becomes clinically apparent within
the 1st 6 yr of life. In addition to megaloblastic anemia, the patient may also
have neurologic defects (e.g., hypotonia, developmentaldelay, brain atrophy,
movement disorders, dementia) and/or proteinuria.
18.(D) Thiamine-responsive megaloblastic anemia (Rogers syndrome) is a very
rare autosomal recessive disorder characterized by megaloblastic anemia,
sensorineural deafness, and diabetes mellitus. Congenital heart defects,
arrhythmias, visual problems, short stature, trilineage myelodysplasia, and
strokes are also described. Thiamine-responsive megaloblastic anemia usually
presents in infancy but may occasionally developin childhood and adolescence
and occurs in several ethnically distinctpopulations. The bone marrow is
characterized not only by megaloblastic changes but also by ringed sideroblasts.
Continuous thiamine supplementation usually reverses the anemia and
diabetes, but not existinghearing defects.
19.(A) It is therefore necessary to absorb approximately 1 mg daily to maintain
positive iron balance in childhood. Because <10% of dietary iron is usually
absorbed, a dietary intake of 8-10 mg of iron daily is necessary to maintain iron
levels.
20.(D) When the hemoglobin level falls to <5 g/dL, irritability, anorexia, and
lethargy develop, and systolic flow murmurs are often heard. If the hemoglobin
continues to fall, tachycardia and high output cardiac failure can occur.
21.(E) Detection of increased soluble transferrin receptor and decreased
reticulocyte hemoglobin concentration provides very useful and early indicators
of iron deficiency, but availability of these tests is more limited.
22.(B)
23.(B) Iron therapy may increase the virulence of malaria and certain gram
negative bacteria, particularly in developing countries. Iron over dose is
associated with Yersinia infection.
24.(E) Sickle cells: sickle cell disease
Target cells: hemoglobinopathies (HbC, HbS, thalassemia), liver disease
489
Schistocytes/burr cells/helmet cells/RBC fragments: microangiopathic hemolytic
anemia (DIC, HUS, TTP)
Spherocytes: hereditary spherocytosis, autoimmune hemolyticanemia
Cigar-shaped cells: hereditary elliptocytosis
“Bite” cells: G6PD deficiency
Poikilocytosis, microcytosis, fragmented erythrocytes, elliptocytes:hereditary
pyropoikilocytosis
25.(D) The mean corpuscular volume (MCV) of HS erythrocytes is low normal or
even slightly decreased, and the mean corpuscular hemoglobin concentration
(MCHC) is usually increased (>35 g/dL). An MCHC >35.4 g/dL combined with a
red cell distribution width (RDW) <14% has been suggested as a screening test
for HS.
26.(A) Isoimmune hemolytic disease of the newborn, particularly when a result
of ABO incompatibility, closely mimics the appearance of HS. The detectionof
antibody on an infant’s RBCs using a direct antiglobulin (Coombs)test should
establish the diagnosis of immune hemolysis.
27.(D) Most experts recommend splenectomy for patients with severe HS and
believe it should be strongly considered for patients with moderate HS and
frequent hypoplastic or aplastic crises, poor growth, or cardiomegaly.
It is generally not recommended for patients with mild HS. When splenectomy
is indicated, it should be performed after age 6 yr.
28.(A) HPP is characterized by extreme microcytosis (mean corpuscular volume,
50-65 fL/cell), extraordinary variation in cell size and shape, and
microspherocytosis with occasional elliptocytosis.
29.(B) Hereditary xerocytosis (HX), the most common type of the hereditary
stomatocytosis syndromes, is a dominant disorder of erythrocyte dehydration.
Affected patients exhibit a mild compensated macrocytic hemolyticanemia with
variable degrees of splenomegaly and intermittent jaundice. The MCHC and
MCV are elevated, erythrocyte osmotic fragility isdecreased, and K+
concentration and total monovalent cation contentare decreased. There are
small numbers of stomatocytes, target cells,and contracted RBCs with
hemoglobin puddled to the side on peripheralblood smear.
30.(D) Tangier disease, familial deficiency of high-density lipoproteins(HDLs) is a
rare recessive disorder that results from mutationsin the cholesterol and
phospholipid transport protein ABCA1, leading to perturbations of cellular
cholesterol transport, and resulting in the accumulation of cholesterol esters in
many tissues. Hematologic manifestations include a mild to moderate
stomatocytic hemolytic anemia and thrombocytopenia. Affected patients can
490
also have large orange tonsils, hepatosplenomegaly, lymphadenopathy, cloudy
corneas, peripheralneuropathy, and premature atherosclerosis.
31.(D) Pancytopenia with bone marrow infiltration can be seen in metastatic
solid tumors, myelofibrosis, hemophagocytic lymphohistiocytosis, and
osteopetrosis.
32.(B) Inherited pancytopenias account for approximately 30% of cases of
pediatric bone marrow failure. Fanconi anemia is considered the most common
of the inherited pancytopenias.
33.(B) Amegakaryocytic thrombocytopenia with radioulnar synostosis
characterized by thrombocytopenia with progression to pancytopenia. It could
be associated with acute myeloid leukemia. The gene is HOXA11.
34.(C) Pearson marrow-pancreas syndrome is characterized by neutropenia
with progression to pancytopenia. The gene is mtDNA deletion.
35.(E) The most common congenital anomalies in FA are skeletal and include
absence of radii and/or thumbs that are hypoplastic, supernumerary, bifid, or
absent. Anomalies of the feet, congenital hip dislocation, and leg abnormalities
can also be seen.
36.(A) Thrombocytopenia, red blood cell (RBC) macrocytosis, and increased
hemoglobin F, as a result of bone marrow stress, often appear first.
Subsequently, patients develop neutropenia and then anemia.
37.(C) Complete blood count shows pancytopenia; bone marrow aspiration and
biopsy confirms the hypoplasia of the marrow; chromosomal breakage test is
the most commonly available and detects the increased fragility with and
without addition of the cross-linking agents but still 10-15% have somatic
mosaicism and may not show the high degree of chromosomal fragility; Next-
generation sequencing has largely replaced the need for 2-step genetic testing
(complementation group testing followed by targeted gene testing) and is most
often used.
38.(B)
39.(B) AML, MDS, and rare head, neck and skin tumors.
40.(D) Reticulocytosis and a rise in hemoglobin within 1-2 mo. White blood cell
(WBC) counts may increase next, followed by platelet counts.
41.(B) Oral oxymetholone and danazol are the 2 most commonly used
androgenic drugs.
42.(E) A response is expected in 70% of patients, treatment is a bridge rather
than curative while awaiting for a suitable donor for HSCT or while weighing
the risks and benefits of transplant, If a low dose is initially employed, the
androgen dose can be increased every 3-4 wk as long as no major side effects
491
are seen and until the desired response is achieved. If a high dose is initially
employed, androgen dosage can be slowly reduced to the minimum dose that
maintains the required blood counts. Side effects of androgens include
masculinization, increased linear growth, increased mood swings or
aggressiveness, elevated hepatic enzymes, cholestasis, peliosishepatis, and liver
tumors. Screening for these should be performed regularly. Patients typically
stop responding to androgens after several months or years, as their bone
marrow failure progresses or as they develop MDS or AML.
43.(C) A heightened risk of expansion of bone marrow cells with clonal
cytogenetic abnormalities such as monosomy 7. All other items are true but not
a limitation for initiating therapy.
44.(D)
45.(B) Neutropenia 90%, anemia 46%, thrombocytopenia 42%, and
pancytopenia 21%.
46.(A) Exocrine pancreatic insufficiency 98%, elevated transaminase 61%,
skeletal abnormality 70%, rib cage abnormality 35% and short stature 66%.
47.(C)
48.(C) Although skeletal abnormalities are variable in Shwachman-diamond
syndrome, classic findings are metaphyseal dysplasia, osteopenia, delayed
appearance of secondary ossification centers, short or flared ribs, and thoracic
dystrophy.
49.(A) Isochromosome 7q is particularly common, suggesting that it is a fairly
specific clonal marker of SDS and might be related to the presence of mutant
SBDS on 7q11. Other clonal chromosome abnormalities include monosomy 7,
i(7q) combined with monosomy 7, deletions or translocations involving part of
7q, and deletions of 20q [Del(20q)].
50.(A) A diagnostic triad of mucocutaneous features was proposed when the
disorder was first described and included dysplastic nails, lacy reticular
pigmentation of the upper chest and/or neck, and oral leukoplakia. However,
the triad is not present in all individuals.
51.(D) Skin pigmentation is the commonest (89%) followed by nail dystrophy
(88%).
52.(C) Revesz syndrome has many of the features of DC and presents in early
childhood in addition to Bilateral exudative retinopathy is required to establish
a diagnosis. Patients may also have intracranial calcifications, IUGR,
developmental delay, and bone marrow failure.
53.(C) Owing to additional risk of liver and pulmonary fibrosis.

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54.(D) The most common anomalies are neurologic and cardiac. Findings
related to cerebellar and cerebral atrophy are frequent, and developmental
delay is a prominent feature. Congenital heart disease includes atrial and
ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, and
coarctation of the aorta.
55.(B)
56.(C) Cytomegalovirus, Epstein-Barr, Hepatitis B, Hepatitis C, Hepatitis non-A,
non-B, non-C (seronegative hepatitis) and HIV. Parvovirus B19 is classically
associated with isolated red blood cell (RBC) aplasia, but in patients with sickle
cell disease or immunodeficiency, it can result in transient pancytopenia.
57.(B) Dose dependent (Chloramphenicol, dapsone, fluorocytosine), and dose
independent (Chloramphenicol, dapsone, sulfonamides, tetracycline,
methicillin, amphotericin, quinacrine, chloroquine, pyrimethamine).
58.(B) Severe aplastic anemia is defined as a condition in which ≥2 cell
components have become seriously compromised (absolute neutrophil count
<500/mm3, platelet count <20,000/mm3, reticulocyte count <1% after
correction for hematocrit) in a patient whose bone marrow biopsy material has
<30% cellularity.
59.(C)
60.(A)
61.(C)
62.(E) Presence of JAK2 or similar mutation. (A) is a major criterion if >25%.
63.(A)
64.(A) Phlebotomy is the initial treatment of choice to alleviate symptoms of
hyperviscosity and decrease the risk of thrombosis.
65.(B) Maintain hemoglobin >12.0 g/dl and severe pulmonary disease; maintain
hemoglobin >12.0 g/dl during extracorporeal membrane oxygenation; maintain
hemoglobin >10.0 g/dl and moderate pulmonary disease; maintain hemoglobin
>12.0 g/dl and severe cardiac disease; maintain hemoglobin >10.0 g/dL
preoperatively and during major surgery; maintain hemoglobin >7.0 g/dL
postoperatively; and maintain hemoglobin >7.0 g/dL and symptomatic anemia.
66.(D) Another factor is the rapid disappearance of EPO from infant plasma (i.e.,
accelerated metabolism).
67.(D)
68.(C)
69.(E) In patients with inherited disorders, PLT transfusions are justified only if
the risk of significant bleeding is quite high or if bleeding is overt, because

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inherited PLT dysfunction often is lifelong and repeated transfusions may lead
to alloimmunization and refractoriness.
70.(E) For infants below 4 months, granulocyte transfusion is indicated with
blood neutrophil count <3.0 × 109 /L in 1st wk of life or <1.0 × 109 /L thereafter
and fulminant bacterial infection.
71.(C) Certain diseases, such as hypothyroidism, and medications, such as
valproic acid, can lower VWF levels in affected patients. Repeat testing may be
required to rule out or confirm a diagnosis of VWD. Other choices increase the
level.
72.(E) Characterized by a defect in the ability of VWF to bind FVIII, also low
factor VIII is seen in Type 3.
73.(C) 2B and platelet-type VWD.
74.(A) Desmopressin is beneficial in Type 1 and some type 2VWD with caution.
75.(E)
76.(B)
77.(B) Leukopenia suggests another diagnosis.
78.(A) Chronic Immune thrombocytopenia is an indication for autoimmune
assay.
79.(B) Isolated enlargement of the spleen suggests the potential for
hypersplenism caused by liver disease or portal vein thrombosis.
80.(B) Autoimmune thrombocytopenia may be an initial manifestation of SLE,
HIV infection, common variable immunodeficiency, and rarely, lymphoma or
autoimmune lymphoproliferative syndrome.
81.(A) Observation in this condition is best and inexpensive.
82.(C) Rapid elevation of platelets is needed in cases of social hyperactivity.
83.(B) It gives 80% cure.
84.(B) The majority of patients have mild symptoms despite severe
thrombocytopenia, early therapy does not affect the outcome of disease,
transfused platelets are liable for destruction so as the autologous platelets, and
observation and watchful waiting is the best current strategy in cases of mild
bleeding.
85.(D) The role of splenectomy in ITP should be reserved for 2 circumstances:
(1) the older child (≥4 yr) with severe ITP that has lasted >1 yr (chronic ITP) and
whose symptoms are not easily controlled with therapy and (2) when life-
threatening hemorrhage (ICH) complicates acute ITP, if the platelet count
cannot be corrected rapidly with transfusion of platelets and administration of
IVIG and corticosteroids.

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86.(C) Autoimmune disease (e.g., SLE), chronic infectious disorders (e.g., HIV),
and nonimmune causes of chronic thrombocytopenia, such as type 2B and
platelet- type von Willebrand disease, X-linked thrombocytopenia, autoimmune
lymphoproliferative syndrome, common variable immunodeficiency syndrome,
autosomal macrothrombocytopenia, and Wiskott-Aldrich syndrome
87.(A)
88.(B)
89.(E) Effective in 80–95% of patient.
90.(E) Findings in the BMA study are diagnostic.
91.(A) Intolerance to cow's milk formula (present in 50%) may complicate
management by triggering gastrointestinal bleeding, increased
thrombocytopenia, eosinophilia, and a leukemoid reaction.
92.(B) MYH9-related thrombocytopeniacomprises a number of diverse
hereditary thrombocytopenia syndromes (e.g., Sebastian, Epstein, May-Hegglin,
Fechtner) characterized by autosomal dominant macrothrombocytopenia,
neutrophil inclusion bodies, and a variety of physical anomalies, including
sensorineural deafness, renal disease, and eye disease.
93.(E)
94.(D) Splenomegaly may result from obstruction in the hepatic, portal, or
splenic veins leading to hypersplenism. Wilson disease, galactosemia, biliary
atresia, and α1-antitrypsin deficiency may result in hepatic inflammation,
fibrosis, and vascular obstruction.
95.(B)
96.(A) Howell-Jolly bodies is seen in sickle cell disease, basophilic stippling in
lead and heavy metal poisoning, Pappenheimer bodies in sideroblastic anemia,
Cabot rings in megaloblastic anemia, and hemoglobin crystals in hemoglobin C
disease.
97.(A) Group A streptococci and Staphylococcus aureus.
98.(B) A firm, fixed node should always raise the question of malignancy,
regardless of the presence or absence of systemic symptoms or other abnormal
physical findings.
99.(D) A prolonged course is more suggestive of infectious agents rather than
bacteria.
100.(E)
101.(B) HHV-8 may stimulate excessive production of interleukin-6 (IL-6).
102.(D)
103.(A)

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Chapter 21
Cancer and Benign Tumors
Questions
HASANEIN H. GHALI
1. Which one of the following malignancies is associated with the use of
alkylating agents?
A. Brain tumors
B. Hodgkin disease
C. Osteosarcoma
D. Neuroblastoma
E. Hepatoblastoma

2. Which of the following viruses is associated with the development of Kaposi

sarcoma?
A. Epstein-Barr virus
B. Human herpes virus
C. Hepatitis B virus
D. Hepatitis C virus
E. Human papilloma virus

3. The development of cancer that is linked to genomic imprinting is best

represented by:
A. Bloom syndrome
B. Trisomy 21
C. Beckwith-Wiedemann syndrome
D. Ataxia telangiectasia
E. Wiskott-Aldrich syndrome

4. Which of the following agents has a side effect of pseudotumor cerebri?

A. Methotrexate
B. Vinblastine
C. Cytarabine
D. Tretinoin
E. Etoposide

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