Anemia

in
Childhood
Hemato - Oncology Division
Departement of Child Health
School of Medicine
University of Sumatera Utara
1

Anemia
Definition
Condition in which the concentration of
Hemoglobin
or the red cell mass is reduced below normal

Table 1. Normal red blood cell values in childre

Hemoglobin (g/dl)
AGE
Birth (cord blood)
1-3 days (capillary)
1 week
2 weeks
1 month
2 months
3-6 months
0.5-2 years
2-6 years
6-12 years
12-18 years, female
12-18 years, male
18-49 years, female
18-49 years, male

MCV (fl)

Mean

- 2 SD

Mean

- 2 SD

16.5
18.5
17.5
16.5
14.0
11.5
11.5
12.0
12.5
13.5
14.0
14.5
14.0
15.5

13.5
14.5
13.5
12.5
10.0
9.0
9.5
10.5
11.5
11.5
12.0
13.0
12.0
13.5

108
108
107
105
104
96
91
78
81
86
90
88
90
90

98
95
88
86
85
77
74
70
75
77
78
78
80
80

Hasting, C. Anemia , In: Hematology/oncology handbook,

2002 ; 3

MORPHOLOGY

Normocytic
Normochrom
ic

1. Acute blodd
loss
2. Hemolytic
anemias

Microcytic
Normochro
mic

1. Hberythrocyte
mass deficit

3. Hberythrocyte
mass deficit

Miller, DR. Anemias: general considerationd, in :

Microcytic
Hypochrom
ic

Macrocytic
Normochromi
c

1. Iron def.
anemia

1. Pernicious
anemia

2. Thalassemia
synd.

2. Megaloblasti
c anemias

3. Chronic lead
poisoning

3. Gastrointesti
nal
abnormalitie
s

4. Miscellaneou
s rare
disorder
; 111-112

.. Klasifikasi anemia

ETIOLOGY
Exessive
blood
destruction

Blood loss
(Acute & Chronic
hemorrhage)

1. Intracorpuscular
a. Defect of
membrane
b. Defect of Hb
c. Defect of enzymes
d. Disorder of
erythroid cell
division
2. Extracorpuscular
a. Immune
b. Non Immune
3. Ineraction of intr and
extracorpuscular factor

r, DR. Anemias: general considerationd, in :

1. Internal
2. External

; 111-112

Decreased or
impaired
production

1. Def. of subtances
for Hb and red cell
formation
2. Depression/inhibitio
n BM
3. Malignancies
4. Infection, endocrine
disorder, chronic
inflam. Diseases,
etc
5. Dyserthyropoiesis

.. Klasifikasi anem

Table 2. Classification of Nature of the Anemia

Based on
MCV and RDW
RDW
Normal

RDW high

MCV Low

MCV Normal

MCV High

Microcytic
Homogenous

Normocytic Homogeneous

Macrocytic
Homogeneous

Heterozygous
Thalassemia
Chronic disease

Normal
Chronic disease
Chronic liver disease
Nonanemic
Hemoglobinopathy
(e.g., AS, AC)
Transfusion
Chemotherapy
Chronic
myelocytic
leukemia
Hemorrhage
Hereditary spherocytosis

Micricytic
Heterogeneous

Normocytic
Heterogeneous

Iron deficiency
S -yhalassemia
Hemoglobin H
Red cell
fragmentation

Early
iron
of
deficiency
Mixed deficiencies
Hemoglobinopathy
(e.g., AS. AC)
Myelofibrosis
Sideroblastic anemia

Aplastic anemia
Preleukemia

Macrocytic
Heterogeneous
folate

Folate deficiency
Vitamin
B12
deficiency
Immune hemolytic
anemia
Cold agglutinins

Asses degree of Anemia

Mild

Moderate

Severe

(Hb > 10 g/dl)

(Hb 7-10 g/dl)

(Hb <7 g/dl)

History and physical

examamination
Compatible with iron
deficiency

History, physical
examination
Iron studies
(Hb
electrophoresis)
Family studies

or

Trial of oral iron 4-6

mg/kg/day
Dietary counselling
Reticulocyte count at
1 week

Deficient
Not Improved

Improved
Continue oral Fe 3-6 months

Blood loss (urinalysis, stool

guaiac, Meckels scan)
Hemolysis (Coomb test,
perpheral smear)
Hemoglobinopathy/thalassem
ia
Hb electrophoresis
Family studies
Lead poisoning
Iron studies, Iron
malabsorption
Oral iron challenge,
consider parenteral iron

Iron studies
(FEP, Fe/TIBC, %
transferin sat.)
Suggestive
smear
Reticulocyte
count
Stool guaiac

Hospitalization
Consider :Transfusion
Iv or oral iron (if
indicated)

Hemogloinopathy /
thalassemia
(Hb electrophoresis,
family studies)
Lead toxicity

Severe iron deficiency

Red cell aplasia
Malignancies
Infection
Hemolytic anemia with
illness/infection
Thalassemia
Thalassemia mayor, Hb
H diseases
Hemoglobinopathies
Sickle cell

Hasting, C. Anemia , In: Hematology/oncology handbook, 2002 ; 2

Investigation of Anemia
Anemi
a
MCV

Low
History, physical examination,
CBC
Compatible with iron
deficiency

Reticulocyte
count
Low

High

No
Hemolysis

Response to
Trial of iron

Iron
deficiency

Peripheral
smear

No

Yes

Yes

Normal or high

Neutrophil
s,
platelets
No

Laboratory
evaluation of
microcytic anemia
Low
Bone marrow
failure

Hemolysis

Peripher
al
smear
No
Hemolys
is
Investigate
Blood loss

Specific tests
Dictated by
history,
physical, &
red cell
morphology
Normal or high
Pure red cell
aplasia or
10
megaloblatic

Table 3. Physical examination of the anemic

child
Physical findings
Consider
Skin

Pallor
Jaundice
Petechiae, purpura

Head

Cavernous
hemangioma
Frontal bossing,
prominent malar &
maxillary bones
Icteric sclerae

Severe anemia
Hemolytic anemia, acute & chronic Hepatitis,
aplastic anemia
Autoimmune haemolytic anemia with
thrombocytopenia
Hemolytic-uremic syndrome
Bone marrow aplasia or infiltration
Microangiopathic hemolytic anemia
Extramedullary hematopoiesis (thalassemia major,
congenital hemolytic anemia)
Congenital hemolytic anemia & or hyperhemolytic
crisis associated with infection
Iron deficiency
Vit. B12 or iron deficiency

Angular stomatitis
Glossitis
Chest

Rales, gallop rhythm

Tachycardia

Congestive heart failure, acute or severe anemia

Extremiti
es

Radial limb dysplasia

Spoon nails
Triphalangeal thumbs

Fanconis anemia
Iron deficiency
Hasting, C. Anemia , In: Hematology/oncology handbook, 200
Red cell aplasia

Spleen

Splenomegaly

Congenital hemolytic anemia, infection, hematologic

7
malignancies, portal hypertension with resultant

11

Diagnostic Approach To The Child With Anemia

Microcytic
MCV <1 75
f
Iron deficiency
Dietary
Chronic blood
loss
Thalassemia or
Lead toxicity
Chronic/diseases
infection
Severe malnutrition
Siderobalstic
anemia
Iron studies (RDW,
FEP, Ferritin, Fe/TIBC)
Hb electophoresis
Lead level
Family studies
Check newborn screen
Oral iron challenge

History, physical
examination
CBC, Reticulocyte count
Peripheral blood smear
Normocytic
MCV 75-100 f

Early iron deficiency

Acute blood loss
Red cell enzyme
deficiency
Red cell membrane
defect
Hemolysis
Red cell aplasia
Aplastic anemia
Malignancy
Hypersplenism & drugs

Macrocytic
MCV > 100 f

Normal newborn
Reticulocytosis
Post-splenectomy
Liver diseases
Aplastic anemia
Hyperthyroidism
Down Syndrome
Preleukemia
Megaloblastic anemia
Folic acid def. ,Vit
B12
def. Dietary,
Pernicious
anemia

LFT, Thyroid function

tests
Hb electophoresis, Folic
acid level,
Red cell serum, Vit B12
level, BMP

Red cell enzyme panel

G6PD, pyruvate kinase
Lektacytometri, Coomb
test
12
Hb electrophoresis,
Hasting, C. BMP
Anemia , In: Hematology/oncology handbook, 2002 ; 2

Iron Deficiency Anemia

Definition :
Anemia resulting from lack of sufficient iron for
synthesis of hemoglobin.
Prevalence :
The most common cause of anemia worlwide
An estimated 30% of the worlds population :
4.5 billion anemic
500 600 million Iron def. anemia
North American (1970): 30-75% of child 12 years of
age
Israelli : 25% females (aged 16 - 17 yrs)
Indonesia : 25 35% (aged 5 yrs)
13

Iron cycle

14

12

Etiology
Increased physiologic requirements :
Rapid growth, menstruation, pregnancy
Decreased iron assimilation :
Iron poor diet
Iron malabsorption (pica, sprue, gastric resection)
Blood loss :
Gastrointestinal bleeding
Fetal-maternal transfusion
Hemoglobinuria
Iatrogenic
Idiopathic pulmonary hemosiderosis
Intense exercise
15

Clinical Manifestations
Consequences of anemia :
Mild moderate iron def. ( Hb 6-10 g/dl) :
compensatory mechanism (+)
Severe iron deficiency (Hb < 5 g/dl) :
Fatigue, listlessness, irritability, anorexia,
tachycardia, car- diac dilatation & systolic
murmurs.
Advanced iron deficiency :
Pale, plump, & petulant

16

Clinical Manifestations
Nonhematologic consequence :
Pica :
Phagophagia (compulsive eating of ice)
Geophagia : interest in dirt consumption
risk for parasitic infestation & lead poisoning)
Ephitelial changes : Koilonychia, atrophy of
lingual papil
Exercise intolerance
Behavioral changes
Abnormal thermogenesis
Altered host response
17

Koilonychia

18

Laboratorium Findings
Red blood cells (RBCs)
Hb concentration :
Chronic iron def. red cell indices (MCV, MCH,
MCHC) : parallels with Hb concentration
Reticulocytes : slightly
Red cell morphology :
Mild iron def. hypochromic, anisocytosis
Chronic iron def. poicylocytosis (targets cells,
ovalo-cytes, mycrocytes & cell fragments)
RBCs survival : shortened

19

Live Blood Cell Analysis

Photos taken with a dark field microscope

Normal Red Blood Cell

Microcytes

20

21

Poikylocytosis

Anisocytosis22

 Laboratorium findings

Bone marrow : because hyperplasia of red cells

precur- sors
Platelets
: to 2 4x normal
Iron metabolism :
Serum iron :
TIBC :
Transferrin sat. (ratio SI : TIBC) :
Serum ferritin : < 10 -12 g/dl
FEP (Free erythrocyte porphyrin) : > 100 g/dl
Factor VIII activity : 2 3 fold.
23

Diagnos
is

Based of :
History
Physical examination
Laboratorium findings
Diagnostic criterias for iron deficiency anemia
(IDA) :
Criteria of IDA by WHO :
1. Hb concentration < normal (age dependent)
2. Mean Hb concentration < 31% ( N: 32 - 35%)
3. Serum iron < 50 g/dl (N: 80-180 g/dl)
4. Transferrin sat. < 15 (N: 20-50%)
24

 Diagnosis

Criteria of IDA by Cook & Monsen :

1. Microcytic hypochromic anemia
2. Transferrin sat. < 16%
3. FEP levels > 100 ug/dl eritrosit
4. Serum ferritin level < 12 u/dl
.. Diagnostic to established if 2 from 3
criterias
(Transferrin sat. serum ferritin & FEP) are
present.

25

 Diagnosis

Criteria of IDA by Lanzkowsky :

1. Peripheral smears :
- Microcytic hypochromic
- MCV, MCH, MCHC :
- RDW > 17%
2. FEP :
3. Serum ferritin :
4. Serum ferritin , TIBC , Transferrin sat. < 16%
5. Response to iron preparation
6. Bone marrow : Iron (-) /
26

Differential Diagnosis
Thalassemia trait
Thalassemia trait
Anemia of chronic diseases & infection
Lead poisoning

27

Treatment

Treatment of IDA is twofold :

Replenishment of body iron
Correction of the factors responsible for
the deficiency
Iron can be administered orally, IM, or IV.

28

.. Treatment

Oral iron therapy

Ferrous salt : adsorbed 3X better than ferric salts
Ferrous gluconate, ferrous fumarate, & ferrous
sucsinat : well adsorbed but >> expensive
Dose : 4 6 mgkg of elemental iron in three divided doses.
An adequate response to iron therapy : Hb concentration > 1g/dl in 10 days & reticulocytosis
within 3 5 days after starting oral iron
supplementati-on.
Side effect : >> adults than in infants & children
temporary staining of the teeth
29

30

.. Treatment

Parenteral iron therapy

Indicated : for steadfast noncompliance with
oral medication, iron malabsorption, ongoing
iron loss exceed.
Preparation : iron dextran a complex of ferric
hydroxide with molecular weight dextrans.
25% of the iron remains at the injection site
for months staining of the skin.
Dose : weight (kg) x desired increment Hb
(g/dl) x 2.5
31

.. Treatment

Erythropoietin
Recombinant human erythropoietin (EPO)
stimulates proliferation & differentiation of
erythroid precursors in heme synthesis.
A typical starting dose : 150 U/kg (3x a week) IV
or SC
Transfusion therapy
Children with very severe anemia (Hb < 5 g/dl)
Blood is best given : packed red cells by a modified
exchange transfusion avoid expansion of the
blood volume.
32

 Diagnosis

Prevention
Encouragement of breast feeding
Use of iron - fortified infant formulas after
weaning
The introduction of wholes cows milk to 1
years of age
Use of iron fortified infant cereals & ascorbid
acid-rich foods at 4 6 months
Supplemental iron for preterm infants after
the first month.
33

Megaloblastic
Anemias
Definition :

Abnormalities of red blood cell (RBC)

morphology and maturation.
RBC : larger than normal & have open, dispersed
nuclear chromatin, an asynchrony between the
maturation of nucleus & cytoplasm.
Etiology :
Deficiency of folic acid
Deficiency Vitamin B12
Inborn errors of metabolism95%
(rarely)

34

Megaloblastic
anemia

35

Nucleated RBC of megaloblastic

anemia

Reticulocytes

36

33

Folic Acid Deficiency

FOLATES
Abundant in many foods, including green
vegetables, fruits & animals organs.
Heat labile & water soluble
Naturally : polyglutamed form & absorbed
less efficiently than the monoglutamate
species (folic acid).
Folic acid : adsorbed in the small intestine
Megaloblastic anemia : occurs after 2 3
mo on a folate- free diet.
37

34

Etiology
Inadequate folate intake
Anemia due to decreased folate intake becomes
manifest increased vitamin requirements
(pregnancy, growth in infants & chronic hemolysis)
The normal infant daily requirements : 25 35
g/day.
Decreased folate absorption
Malabsorption due to chronic diarrheal states,
diffuse infammatory diseases.
Previous intestinal surgery
Anticonvulsant drugs
38

35

.. Etiology

Acquired and congenital disorders of folate

metabolism :
Megaloblastic anemia : congenital dihydrofolate
reductase deficiency
Drugs induced abnormalities in folate
metabolism :
Methotrexate
Pyrimethamine
Trimethoprim
Therapy : folinic acid is benefial
39

.. Folic acid deficiency

Clinical Manifestations

Megaloblastic anemia : the peak

incidence
at 4- 7 mo of age.
Anemia, irritability, fail to gain weight
adequately, chronic diarrhea.
Hemorrhages from thrombocytopenia
Accompany : kwashiorkor, marasmus,
or sprue.
40

.. Folic acid deficiency

Laboratorium Findings
Anemia is macrocytic (MCV > 100 f)
Reticulocyte count :
Neutopenia & thrombocytopenia
Neutrophils : large & hypersegmented nuclei
Serum folic acid : < 3 ng/ml (N 5 20 ng/ml)
Levels of iron & vit. B12 : N or
LDH serum :
Bone marrow : hypercellular

41

38

.. Folic acid deficiency

Treatment
Diagnosis of folate deficiency is established :
Folic acid can be orally or parenterally
Dose : 0.5 1 mg/day
Specific diagnosis is in doubt :
Smaller dose : 0.1 mg/day for a week diagnostic
test
Transfusion : severe anemia or child is very ill.
Folic acid therapy (0.5 1 mg.day) : should be
continued for 3 4 weeks untills hematologic response
(+).
Maintenace therapy with multivitamin (containing 0.2
folate) is adequate.
42

39

Vitamin B12 Deficiency

Anemia
Vitamin B12
Derived from cobalamin in food ( mainly animal
sources) secondary to production by
microorganism.
Obtained primarily from :
Animal proteins (ie, red meat, poultry, fish,
eggs,
and dairy)
Plants and vegetables lack the vitamin unless
they have been contaminated by soil
microorganisms
43

40

Absorption of vit. B12

44

41

.. Vit. B12 deficiency

Etiology

Inadequate dietary intake of vitamin

Extreme dietary restriction (strict
vegetarians or vegan)
In children : breast-fed infants whose
mothers are vegans or pernicious
anemia
Lack of IF (intrinsic factor) secretion by the
stomach :
Congenital pernicious anemia
Juvenile pernicious anemia
Gastric surgey
45

..

Etiology

Impaired intestinal absorption of IF

cobalamin
Infammatory diseases( regional
enteritis or NEC)
Imerslund-Grasbeck Syndromes)
Absence of vitamin B12 transport
protein

46

43

 Vit B12 deficiency

Clinical Manifestations
Weakness, fatigue, failure to thrive, or irritability
Pallor, glossitis, vomiting, diarrhea, & icterus
Neurologic symptoms : parasthesias, sensory
deficits, hypotonia, seizures, developmental
delay, & neuropsychiatris changes.

47

44

.. Vit. B12 deficiency

Laboratorium findings
Macrocytic anemia (MCV > 100 f)
RBCs : prominent macroovalocytosis
Neutrophil : large & hypersegmented
Neutropenia, thrombocytopenia, simulating
apalstic anemia or leukemia
Serum Vit. B12 levels : < 100 pg/ml
Serum iron & folic acid : Normal / elevated
Seru LDH :
Serum bilirubin levels : moderate elevations (2-3
mg/dl)
Methylmalonic acid in the urine : >>> (N 0 3.5
mg/24hrs)
48

.. Vit.B12 deficiency

Treatment
Parenteral administration of vit. B12 (1mg)
reticulocytosis in 2 4 days
The physiologic requirment for vit. B12 : 1
5 g/day
Minidose : if diagnosis is in doubt
If evidence of neurologic involvement (+) :
dose 1 mg/day (IM) for at least 2 weeks
Maintenance therapy : 1 mg monthly (IM)
Oral therapy : succeed mucosal diffusion
with high dose
49