An 11-month-old African American boy has a hematocrit of 24% on a screening laboratory done

at his well-child check-up. Further testing demonstrates: hemoglobin 7.8 g/dL; hematocrit
22.9%; leukocyte count 12,200/μL with 39% neutrophils, 6% bands, 55% lymphocytes;
hypochromia on smear; free erythrocyte protoporphyrin (FEP) 114 μg/dL; lead level 6 μg/dL
whole blood; platelet count 175,000/μL; reticulocyte count 0.2%; sickle-cell preparation
negative; stool guaiac negative; and mean corpuscular volume (MCV) 64 fL. Which of the
following is the most appropriate recommendation?
a. Blood transfusion
b. Oral ferrous sulfate
c. Intramuscular iron dextran
d. An iron-fortified cereal
e. Calcium EDTA

A healthy 1-year-old child comes to your office for a routine checkup and for immunizations.
His parents have no complaints or concerns. The next day, the CBC you performed as customary
screening for anemia returns with the percentage of eosinophils on the differential to be 30%.
Which of the following is the most likely explanation?
a. Bacterial infections
b. Chronic allergic rhinitis
c. Fungal infections
d. Helminth infestation
e. Tuberculosis

On a routine well-child examination, a 1-year-old boy is noted to be pale. He is in the 75th

percentile for weight and the 25th percentile for length. Results of physical examination are
otherwise normal. His hematocrit is 24%. The answer to which of the following questions is
most likely to be helpful in making a diagnosis?
a. What is the child’s usual daily diet?
b. Did the child receive phototherapy for neonatal jaundice?
c. Has anyone in the family received a blood transfusion?
d. Is the child on any medications?
e. What is the pattern and appearance of his bowel movements?

A previously healthy 2-year-old child is known to have sickle cell disease; she now has a 1-hour
history of left-sided weakness and ataxia. Which of the following therapies is the most
appropriate first step in the management of her likely diagnosis?
a. Iron chelation with deferoxamine
b. Initiation of broad-spectrum antibiotics after obtaining appropriate cultures
c. Cranial ultrasound
d. Arrange for an outpatient MRI of the brain
e. Initiation of a stat blood transfusion

On a routine-screening CBC, a 1-year-old child is noted to have a microcytic anemia. A follow-

up hemoglobin electrophoresis demonstrates an increased concentration of hemoglobin A2. The
most appropriate next step in the management of this child’s condition is which of the following?
a. Initiate oral iron therapy.
b. Provide family counseling alone.
c. Begin oral, daily folate, and penicillin therapy.
d. Arrange for a bone marrow aspiration.
e. Initiate therapy with dimercaptosuccinic acid (Succimer).
4-year-old previously well African American boy is brought to the office by his aunt. She reports
that he developed pallor, dark urine, and jaundice over the past few days. He stays with her, has
not traveled, and has not been exposed to a jaundiced person, but he is taking trimethoprim
sulfamethoxazole for otitis media. The CBC in the office shows a low hemoglobin and
hematocrit, while his “stat” serum electrolytes, blood urea nitrogen (BUN), and chemistries are
remarkable only for an elevation of his bilirubin levels. His aunt seems to recall his 8-year-old
brother having had an “allergic reaction” to aspirin, which also caused a short-lived period of
anemia and jaundice. Which of the following is the most likely cause of this patient’s symptoms?
a. Hepatitis B
b. Hepatitis A
c. Hemolytic-uremic syndrome
d. Gilbert syndrome
e. Glucose-6-phosphate dehydrogenase deficiency

A male infant was found to be jaundiced 12 hours after birth. At 36 hours of age, his serum
bilirubin was 18 mg/dL, hemoglobin concentration was 12.5 g/dL, and reticulocyte count was
9%. Many nucleated RBCs and some spherocytes were seen in the peripheral blood smear. The
differential diagnosis should include which of the following?
a. Pyruvate kinase deficiency
b. Hereditary spherocytosis
c. Sickle-cell anemia
d. Rh incompatibility
e. Polycythemia
 Clinical case

A 22 month old boy presents to your office with a chief complaint of pallor. A visiting relative
who has not seen the child for 5 months told his mother that the boy appears pale. The mother
brings him in for a checkup even though she notices no change in his coloring (he has always
been fair skinned). On review of symptoms you find that he is an active toddler, with no recent
fatigue, exercise intolerance, or increase in sleeping. He has had no blood in his diapers and no
black or tarry stools. He is a picky eater, taking small amounts of chicken, pork and some
vegetables, but loves milk and drinks six to eight bottles of whole milk per day.
Family history reveals a distant aunt who had anemia when she was pregnant but which
subsequently resolved. There is no history of splenectomy, gall stones at an early age, or other
anemia in the family.
Exam: VS: T 37.5, BP 90/52, P 145, RR 16, Height 85.5 cm (50th %ile), Weight 13.2 kg (75th
%ile). General appearance: He is a pale appearing, active toddler, holding a bottle, tearing and
eating paper from your exam table. Eyes: No scleral icterus. Pale conjunctiva.
Mouth: Dental caries. Chest: Clear. Heart: Mild tachycardia as above, grade II/VI systolic
ejection murmur heard best over the upper left sternal border. Abdomen: No
hepatosplenomegaly. Rectal: Dark brown, soft stool, negative for occult blood.
CBC: WBC 6,100, Hgb 6.2 g/dl, Hct 19.8%, Plt 589,000, MCV 54 fL, RDW 17%. Reticulocyte
count is 1.8%. The lab reports microcytosis, hypochromia, mild anisocytosis and polychromasia.
There is no basophilic stippling.

Preliminary diagnosis : Anemia

Plan of investigations
- Physical Examination
- CBC
- iron and serum ferritin measurements

Differential diagnosis

Disease/Condition Differentiating Signs/Symptoms Differentiating Tests

Anemia of chronic Signs and symptoms of underlying CBC and peripheral smear: anemia,
disease chronic disease (e.g., infection, cancer, hypochromia, microcytosis, anisocytosis,
autoimmune disease, kidney disease). and poikilocytosis are less pronounced than
in IDA.
In 80% of cases, anemia of chronic disease
is normocytic and normochromic. However,
in 20% of cases it can present as a
microcytic, hypochromic anemia similar to
IDA.
Ferritin is often elevated in patients with
anemia of chronic disease.
Anemia of chronic disease has a normal
transferrin receptor assay.
Disorders of globin Patients with severe thalassemia are CBC: often more severe microcytosis than
synthesis usually transfusion dependent from expected for the degree of anemia.
(thalassemias, childhood and therefore diagnosed
Hemoglobin: usually reduced.
hemoglobin E, early. Patients with thalassemia minor
hemoglobin C, Red cell distribution width: usually normal in
Disease/Condition Differentiating Signs/Symptoms Differentiating Tests
unstable may not be diagnosed until adulthood. thalassemia.
hemoglobins)
Hemoglobin electrophoresis may help Peripheral smear: more pronounced
distinguish these disorders but can be basophilic stippling and target cells.
normal.
Hemoglobin electrophoresis: elevated
hemoglobin A2 level is a common beta-
thalassemia trait.

Sideroblastic Alcoholism can be a cause of a Peripheral smear: erythrocyte dimorphism

anemias reversible sideroblastic anemia.
Hepatosplenomegaly is found in one
third to one half of patients with
sideroblastic anemia and is not present
in IDA.
(hypochromic, microcytic population mixed
with normal population); erythrocyte
dimorphism is also seen in partially treated
IDA.
Presence of the occasional heavily stippled,
hypochromic cell.
Bone marrow biopsy: ringed sideroblasts
seen because of accumulation of iron in the
mitochondria.

Disorders of A collection of disorders characterized Testing for most of these disorders is not
porphyrin and heme by defective synthesis of porphyrin and readily available.
synthesis heme.
Referral to a hematologist and/or research
A positive family history may be center may be necessary.
present. Neurologic disorders and/or
photosensitivity may be present.

Lead intoxication Patients may have a history of risk
factors for lead exposure such as
occupational exposures (exposure to
lead paint) or distillation of illicit
(illegally produced homemade)
alcohol.
Lead level and free erythrocyte
protoporphyrin (FEP) or zinc protoporphyrin
(ZPP) can be tested. Lead level is increased.
Increased FEP or ZPP can reflect exposure
to lead in previous 3 months (the typical
lifespan of a red cell).

Atransferrinemia Very rare disorder characterized by Serum and bone marrow iron levels: low as
low plasma iron concentration they are in IDA, but, unlike in IDA, total iron-
secondary to a lack of transferrin, binding capacity will also be low. [4]
which normally acts as a specific iron
transport protein.
Transferrin can be given to correct the
disorder.
Antibodies against Case reports exist, but very rare. Iron profile: increased serum iron
the transferrin Clinically, these patients resemble concentration, normal serum ferritin level.
receptor patients with IDA.
FEP: dramatically increased.
Aluminum Occurs primarily in hemodialysis Erythrocyte aluminum levels increased.
intoxication patients if the public water supply is
used as a source of water for dialysis.
Can be avoided with the use of
Disease/Condition Differentiating Signs/Symptoms Differentiating Tests
deionized water and can be reversed
with the use of a deferoxamine
chelator. ]
Copper deficiency Patients often have neurologic Microcytic anemia, increased ferritin, and no
(hereditary abnormalities. serum ceruloplasmin.
aceruloplasminemia)

Gallium History of gallium infusion. History of gallium administration.

administration
Used as diagnostic and therapeutic
agent in cancer, and disorders of
calcium and bone metabolism.
Gallium binds to transferrin and inhibits
cellular iron uptake.
Microcytic hypochromic anemia was
noted in patients treated with gallium in
a phase 2 chemotherapy trial.

Clinical diagnosis : Iron deficiency anemia

Treatment: oral iron therapy and limit milk intake and when his hemoglobin has
completely normalized continue iron therapy for three more months.

Prescription of drugs : iron oral 3 mg/kg - 13 ,2 kg = 39,6 mg

Questions

1. What two classification schemes can be used to narrow down the differential diagnosis of
anemia in children?
Classification by physiologic mechanism and classification by morphologic approach
based on red blood cell size
2. What laboratory finding suggests that an anemia is due to a decreased production of red
blood cells?
Low reticulocyte count.
3. What elements of the history, physical, and laboratory evaluation suggest increased red
cell destruction as the cause of anemia?
History of dark urine. Physical exam of jaundice, scleral icterus, splenomegaly. Lab
results of elevated LDH, elevated bilirubin, elevated serum free hemoglobin, decreased
serum haptoglobin, high reticulocyte count, and positive direct antibody test (DAT, also
known as Coombs test).
4. True/False: Cow's milk exerts a direct toxic effect on the intestinal mucosa of some infants,
leading to microscopic blood loss and iron deficiency anemia.
5. True/False: Children with iron deficiency anemia caused by excessive cow's milk intake often
have a history of black or tarry stools.
6. True/False: The iron content of cow's milk is zero or very close to zero.
7. The lab reports a patient's hemoglobin as 7 g/dl, and the reticulocyte count as 1%. The
published normal value for the reticulocyte count is 0.7% to 2.0%, so the reticulocyte count is
within the laboratory's normal range. How would you interpret this reticulocyte count?
a. This reticulocyte count is normal, so the patient's bone marrow is making RBCs adequately.
b. This reticulocyte count is low. The laboratory's normal values are incorrect.
c. This reticulocyte count value is normal for a patient with a normal hemoglobin, but for a
severely anemic patient, the reticulocyte count should be high. Thus, in view of this patient's
severe anemia, this patient's reticulocyte count is actually low and indicative of a condition in
which RBCs are not being produced.
d. This reticulocyte count is too high for a low hemoglobin. Thus, this is indicative of a
hemolytic etiology.
Clinical case

A 12 month old female of Hawaiian, Chinese, Portuguese and Japanese ethnicity is noted to have
a hemoglobin of 9.1 g/dl with an MCV of 58 on a routine CBC screen at her one year well child
check up. She is otherwise healthy and has no complaints. PE is normal. On a review of this
child's medical record, you note the presence of Hemoglobin Barts on her newborn screen.

Preliminary diagnosis: anemia

Plan of investigations:

CBC:.

Hemoglobin: usually reduced.

Red cell distribution width: usually normal in thalassemia.

Peripheral smear: more pronounced basophilic stippling and target cells.

hemoglobin electrophoresis is normal

hemogram demonstrates microcytic indices
bilirubin

Differential diagnosis :
Clinical diagnosis : Since the child had Hemoglobin Barts on the newborn screen, a form of
alpha thalassemia is present.
Treatment- benign condition
Prescription of essential drugs : oral iron chelation

Questions

1. In reference to the case presentation at the beginning of the chapter, what is the best approach
to an otherwise healthy, asymptomatic 12 month old female with the hemoglobin of 9.1 g/dl
(MCV 58) on routine CBC screen and the presence of Hemoglobin Barts on her newborn screen?
a. explain to the parents that the baby may have thalassemia and obtain an electrophoresis.
b. start the baby on Fe supplements and order an electrophoresis.
c. start the baby on Fe supplements, recheck in a month, and if the hemoglobin is not improved
then, assume the baby has thalassemia.
d. counsel the family that the baby has a form of alpha thalassemia, and that no immediate other
tests or Fe supplements are needed.

2. A newborn Laotian boy is noted to have Hemoglobin E on his newborn screen. He is

otherwise well. A family history is not available due to a language barrier. What is the least
pertinent issue to be considered here?
a. presence of Hemoglobin Barts
b. hemoglobin at 6 months of age
c. hemoglobin level now
d. the order of the hemoglobins printed on the newborn screen

3. Indicate whether iron supplementation is indicated or contraindicated in each of the following

clinical situations.
a. Menstruating female with a hemoglobin of 10.0 g/dl., with no known hemoglobinopathies.
b. Beta thalassemia patient who just lost a modest amount of blood from a scalp laceration.
Hemoglobin is 9.5 g/dl.
c. Healthy alpha thalassemia trait male who wants to build up his hemoglobin to run a marathon.
d. Menstruating female with alpha thalassemia trait who has had heavy and prolonged periods
for the past year. Her hemoglobin is 8.0 and her iron levels and ferritin demonstrate severe iron
deficiency.

Clinical case

A 6 year old girl with sickle cell anemia, who is well known to ED personnel, presents with URI
symptoms for 2 days, and fever to 38.9 (102 F). The URI symptoms consist of a stuffy nose, no
rhinorrhea, and a dry cough, which has not interrupted her sleep. Oral intake has been decreased,
but adequate. She has been given acetaminophen and over the counter cold medications. She also
takes daily prophylactic amoxicillin.
Exam: VS T37.7, P 100, R 30, BP 98/52. She is nontoxic appearing. She has anicteric sclera,
clear conjunctiva, mild clear white nasal discharge, a non-injected pharynx and normal TMs. No
cough is heard during the exam. Her lungs are clear to auscultation. Her heart is regular without
murmurs. Her abdomen is soft and non-tender to palpation. Her spleen in not palpated below the
left costal margin, and her liver is palpated 2 cm below the right coastal margin. There are no
rashes or skin lesions, and she moves all extremities well.
A CBC and blood culture are drawn.

Preliminary diagnosis
Plan of investigations
-hemoglobin electrophoresis
Differential diagnosis
Clinical diagnosis
Treatment
Prescription of essential drugs

Questions

1. Of the following, what is the best approach for a febrile child with sickle cell disease?
a. CBC, BC, oral hydration, IM or oral antibiotics if source of infection is noted on PE.
b. CBC, BC, IM ceftriaxone, follow-up with PCP next day.
c. CBC, BC, admit for IV hydration and IV antibiotics.
d. CBC, BC, no oral antibiotics if no specific source of infection is noted on PE.

2. A 13 year old girl with sickle cell anemia is admitted to the hospital for treatment of a pain
crisis. She states her right arm and shoulder started hurting yesterday evening. She has taken
acetaminophen with codeine every 3 hours for the last 8 hours, but the pain has only escalated.
She denies recent fevers, cough, or URI symptoms. She is on no routine pain medications at
home, and was last admitted 5 months ago with a similar pain crisis. On PE, she is in obvious
pain, and is crying. Her exam is remarkable for pallor, and slight sclera icterus. She has full
range of motion of the right arm, and the rest of her joints. CBC shows a hemoglobin of 7.9 g/dl,
WBC 17.8, and platelet count of 543 thousand. Appropriate initial management includes:
a. IV hydration if oral intake is insufficient, IV or PO pain management as needed.
b. IV hydration, hydromorphone PCA plus continuous infusion.
c. IV hydration, IM meperidine prn.
d. IV hydration, transfusion of PRBC, IV narcotic q 4 hours prn.

3. Explain why most states have adopted newborn screens that identify sickle cell disease at
birth.

4. Explain why children with sickle cell disease do not develop symptoms until after 6 months of
age?

Clinical case

This 2-1/2 year old male is referred to the pediatric hematologist with a chief complaint of easy
bruising, nosebleeds and decreased activity for one week. He has no history of fever or appetite
changes. His past medical history is unremarkable. There is no travel history, history of recent
illnesses, or known exposure to toxins.
Exam: He is a well developed, well nourished, pale boy in no acute distress. His conjunctivae are
pale. Sclera are anicteric. TMs are normal. His oral mucosa is moist and shows rare petechiae on
the buccal mucosa. He has some small palpable posterior cervical lymph nodes. He has a sinus
tachycardia with a grade I/VI systolic ejection murmur, without a gallop. His lungs are clear to
auscultation. His abdomen is soft and nontender with normoactive bowel sounds. He has no
palpable masses, hepatosplenomegaly, or inguinal hernias. His penis and testes are normal (no
masses). He has no rashes, but he has ecchymoses present on his left shoulder, chin and both
lower extremities. Petechiae are present on his extremities and groin.
Labs: Hemoglobin 7.9 g/dl, hematocrit 24%, platelet count 12,000, WBC 3,000 with 90%
lymphocytes (absolute neutrophil count 210). Reticulocyte count 0.5%. A bone marrow aspirate
and biopsy show a markedly hypocellular marrow (12% cellularity) with decreased
megakaryocytes and erythroid and myeloid precursors. Bone marrow cytogenetics are normal. A
diepoxybutane test shows no increase in chromosome breakage. Ham's acid serum test is normal.
Serology for CMV, EBV, parvovirus, and hepatitis demonstrates no recent infection.

Preliminary diagnosis
Plan of investigations
Differential diagnosis
Clinical diagnosis
Treatment
Prescription of essential drugs

Questions

1. What is the treatment of choice for severe acquired aplastic anemia?

2. How can one differentiate between Diamond Blackfan anemia and transient
erythroblastopenia of childhood?
3. Name some viruses and drugs which cause aplastic anemia?