Iron Deficiency Anemia in

Adolescent

Definition
Hemoglobin concentration is abnormally low
age, gender, sea-level altitude
as a result of several situation
chronic infection
hereditary blood conditions
deficiency :
folic acid, B12, B6, C,
protein, iron, zinc etc.

THERE IS NO DOUBT THAT IRON DEFICIENCY IS THE

CAUSE OF MOST ANEMIA

Prevalenc
e
USA
o

Infants (9 24 months of age)

Adolescent girls

3 % toddlers
IDA*
3 % adolescent
females
< 1% adolescent
The Indonesian National Household
Health Survey
males
in 2001
: of adolescent girls (10-19 yrs) were
30**%
anemic (Hgb level < 120 g/L)
smaller studies : 22 44%

9% toddlers
:
o 11% adolescent femalesIron def.*
o < 1% adolescent males

India : 60 70% adolescent females***

* LookerAC et.al. JAMA. 1997;277:973-976
** Parmesih dkk. Departemen Kesehatan . 2003
*** Collaboration between Institute for Health Management, Pune &
International Center for Research on Women, Washington, 2000-2003

Nutritional and metabolic aspects of

iron
Iron is one of the most
common elements in the
Earth crust, yet iron
deficiency is the most
common cause of anemia,
affecting about 500 million
people worldwide.
This is because the body has
a limited ability to absorb
iron and excess loss of iron
as a result of hemorrhage is
frequent.

Nutritional and metabolic aspects of iron

Daily iron
cycle
Distribution of
body iron (%)
Hb
65
Ferritin &
Hemosiderin 30
Myoglobin
3,5
Heme-enzymes
(e.g. cytochromes,
catalase,
peroxidase,
Flavoproteins) 0,5
Transferrinbound iron
0,1

Dietary iron
1. Iron is present in food as ferric hydroxides,
ferric-protein and heme-protein complexes.
2. Both the iron content and the proportion of
iron absorbed differ from food to food; in
general, meat-in particular liver-is a better
source than vegetables, eggs or diary foods.
3. The average Western diet contains 10 15 mg
iron daily from which only 5 - 10% is normally
absorbed. The proportion can be increased to
20 30% in iron deficiency or pregnancy but
even in these situations most dietary iron
remain unabsorbed.

Iron absorption

__________________________________________________________________________

Factors favouring absorption Factors reducing absorption

__________________________________________________________________
Heme iron
Inorganic iron
Ferrous form (Fe2+)
Ferric form (Fe3+)
Acids (HCl, vitamin C)
Alkalis-antacids, pancreatic secretions
Solubilizing agents (e.g. sugars, amino acid)
Precipitating agentsphytates,
phosphates
Iron deficiency Iron excess
Ineffective erythropoiesis
Decreased erythropoiesis
Pregnancy
Infection
Hereditary hemochromatosis
Tea
Increased expression of DMT-1 and
Decreased expression of DMT1 and
ferroportin in the duodenal enterocytes ferroportin induodenal
enterocytes
Increased hepcidin
___________________________________________________________________

A model of the pathways of iron absorption by the

entrocyte
Gut
lumen

DMT
1

Fe2+

Enterocyte
Apical

Fe2
+

Fe

Dcyt
b

3+

Fe2
+

Hem
e

Hem
e

Basolater
al
Hephaes
tin

Ferriti
n
Intracellul
ar iron
pool
Heme
oxygenase

Fe2
+

Bloo
d

Fe3+
Transferri
Fe2n

Fe2
+ Ferroportin
+
FeDMT Endocyto
HF transferrin
1
sis
E Fetransferrin
Fe2
+

TfR Transferrin
1

Heme
TfR2
recepto
The figure shows uptake of ionic iron and heme iron from the gut lumen and
r transfer of iron to blood. DMT1, divalent metal transporter 1; HFE,
hemochromatosis protein, TfR 1, transferrin receptor 1; TfR2, transferrin
receptor 2.

Estimated daily iron requirements

(mg/day)
Urine,

Total

Menses Pregnancy
sweat, feces

Adult male
0.5 1
Postmenopausal
female
0.5 1
0.5 1
Menstruating
female*
0.5 1 0.5 1
Pregnant female*
0.5 1
12
1.5 3
Children (average)*
0.5
1.1
Female (age 1215)*
0.5 1 0.5 1
1.6 2.6

Growth

0.5 1

12
0.6
0.6

*These groups are more likely to develop iron deficiency. Therefore these
groups are particularly likely to develop iron deficiency if there is
additional iron loss or prolonged reduced intake.
Puberty: Dietary, Bleeding, Increased demands (i) menstruation; (ii) each
1 kg of weight gain = 80 mL blood and requires 45 mg of iron

Diagnosis
The degrees of iron
deficiency
Iron sufficient

Normal

Iron depletion

Diminishing iron stores

insufficient iron supply

Iron deficiency
(without anemia)
Iron deficiency
anemia

These iron stores are

depleted further and
begin to impair Hb
synthesis
Overt anemia the iron
supply is insufficient to
maintain normal levels of
Hb
10

Clinical Aspects
The signs & symptoms depend on the
degree of deficiency and the rate at which
the anemia develops.
Iron deficiency or mild-to-moderate anemia
may show few, if any, signs or symptoms.
- Pallor
Iron Deficiency Anemia-- Fatigue
-Even severe anemia
- Exercise intolerance
may be asymptomatic
- Tachycardia
- Cardiac dilatation
- Systolic murmurs
-45 % were diagnosed
- Splenomegaly
incidentally!
- Irritability, anorexia

11

Consequences
systematic condition
anemia
impaired exercise capacity
functional alteration
behavior and cognitive performance
lower mental and motor
(early childhood)
developmental test
School-aged
scores
cognitive achievement children*
adolescent*
lower standardized
math scores

Halterman JS et.al. Pediatrics

2001;107:1381-1386
*

12

Mechanisms
Uncertain
Several hypothesis:
altered neurotransmitter
function
diminished activity of several
enzymes (monoamine oxidase,
aldehyde oxidase)
reduced activity of dopamine
Dd2 receptor
myelination may also be
a brief period of ID during the brain growth spurt
affected
causes a lasting deficit in brain iron, which persists
into adulthood despite correction of the anemia !!

13

 Total body iron

ferritin

To describe
the degrees
of Iron
Deficiency

Transport iron
transferrin
saturation
Serum iron
Hematologic
markers
Biochemical markers
14

Normal mean values for hemoglobin (Hb), hematocrit,

(Hct) and MCV
Hb (g/dL)
Hct (%)
Age
MCV limit
(3)
Mean
Lower
Mean
Lower limit
Mean
(y)
Lower limit
8 11 13,
12,0
40
36
83
76
5
12
14
12,0
41
36
85
78
F
13,
12,5
43
37
84
77
M
5
14,
15
0
12,0
41
36
87
79
17
13,0
46
38
86
78
F
M
14,
0
12,0
42
37
90
80
18
15,
14,0
47
40
90
80
F: 49
female 0 M : male
F
M Oski FA, Brugnara C, Nathan DG. A diagnostic approach to the anemic patient. In:
Data from
Nathan DG, Orkin
SE, Ginsburg D, Look AT, editors. Nathan and Oskis hematology of infancy
14,
and childhood. Philadelphia:
WB Saunders Company; 2003, p. 409
15
0

Hematologic markers for identifying iron

deficiency

Hematologic
Normal
Iron
Iron
deficiency Iron
marker
depletion
without anemia
deficiency
Hemoglob N : 11
N : 11
N : 11
Danemia
:<
in
11
(g/dL)
N : 70
N : 70
N : 70
MCV (fL)
100
100
100
D:<
70
RDW (%)
N : < 15
N : < 15
N : < 15
I : 15
CHr (pg)
N : 29
N : 29
D : < 29
D:<
N: 1 5
Reticuloc
N:15
N:15
29
ytes
MCV: mean corpuscular volume; RDW: red blood cell
D:<1
distribution width; CHr: reticulocyte hemoglobin content;
N=normal; I=increased; D=decreased

Values for ages 6 mo to 2 y

16

Biochemical markers for identifying iron

deficiency
Biochemical
Normal
Iron
Iron deficiency
Iron deficiency
marker
Serum ferritin
(mcg/dL) anemia
Serum iron (mcg/dL)
Total iron-binding
capacity
Transferrin
saturation (%)
Serum transferring
receptor (nmol/L)

N
100
60
N
115
50
N
330
30
N
35
15
N
< 35

depletion
D
< 20
N
< 115
N
360
390
N
< 30
I
35

Dwithout anemia
D
10
< 10
D
D
< 60
< 40
N/I
I
390
410
410
D
D
< 10
< 20
I
I
35
35

N
< 40

I
40

I
70

Zinc
N = normal; I = increased; D = decreased
protoporphyrin/Hem
N
e (mcmol/mol)
< 40
17

Making the Diagnosis :

Sideroblast
ic anemia

Thalasse
mia trait

Microcytic

Iron
deficienc
y
The
results
of
these
tests
diurnal
variation
recent iron
intake

Chronic
disease:
inflammatio
n, infection,
cancer

Lead
poisonin
g

18

Making the Diagnosis

Gold standard : a
direct test-bone
marrow biopsy with
Prussian blue staining
Hematologic tests are
based on RBC features

Too
invasive
routine use.

for

Generally are more

readily available and
less expensive.

Detect iron deficiency

Biochemical tests are
before the onset of
based on iron
anemia.
metabolism
! CHr may help diagnose iron deficiency before
anemia is present
19

Because many of these

tests lack specificity,
several tests
are often
Differential
diagnosis of
microcytosis
used
Marker
Thalassemia
Hb
MCV
RDW
FEP
Serum
iron
TIBC
Ferritin
sTfR
sTfR/log
ferritin
Cytokine
CRP
Hb
Electro.

Iron def.
Chronic
Lead poisoning
Inflammation
Combination
R
R
R
R
R
R
I
N
I
N
R
R
R
N/I
I
R
N
R
N/I
R/N
I
I
N
N/I
I/N
I
R
I
I
N
N
N

I
I
N

I
I
N

Both
N
N
N
I
N
N
N

N
N
A

R=reduced; I=increased; N=normal;A=abnormal

Weiss G, Goodnough LT, 2005; Hoffbrand AV et.al.,2006; Oski FA, 1993

20

The diagnosis of
moderately severe
iron-deficiency anemia
is easy

The diagnosis of mild

forms of iron
deficiency anemia
may present a greater
challenge

MCV
Serum ferritin
Serum iron
Serum iron-binding
capacity
Red-cell
protoporphyrin
Red-cell distribution
width
Hemoglobin after
the laboratory tests
the
of iron
mayinstitution
be less reliable
therapy
the values of irondeficient and ironsufficient persons
overlap considerably
21

In the appropriate clinical

setting :
The important of iron intake history

an abnormally low
Hb/Ht
+
a dietary history of
low iron intake

an abnormally low
Hb/Ht
+
a normal diet
history of adequate
iron intake

Ferriti
n
Strongly
suggest IDA
Response to a
therapeutic
trial
To look for blood
loss e.g., occult
rectal bleeding

22

Therapeutic
trial

Oral iron salts

(ferrous
sulfate)

Presumpti
ve IDA
Children: 3 to
6 mg/kg per
day (qd or tid)
Adolescents:
60 mg/dose
(qd or bid)

IDA
nutritional

The
response to
iron
typically
rapid
Hb increase
1 g/dL
after 1
month of
therapy

23

Preventi
on PRIMARY
PREVENTIO
N
Sufficient dietary iron
must be available from 4
months of age and
through the weaning
period.

SECONDA
RY
PREVENTI
ON

SUPPLEMENTARY IRON
FORTIFICATION OF
FOODS
DIETARY EDUCATION

REGULAR SCREENING
PROMPT DIAGNOSIS
TREATMENT OF IRON
DEFICIENCY
24

Treatment of Iron
Deficiency
Iron
Supplementation
RBC Transfusion
Determining the cause and
correcting the abnormality
Growth spurts, poor dietary
patterns, menstrual losses,
and benign gastrointestinal
bleeding
Oral iron supplementation
usually replaces stores most
efficiently
25

Oral
Supplementation

Iron salts: ferrous sulfate

inexpensive
effective therapy for iron deficiency
frequently complain of
gastrointestinal discomfort,
constipation, bloating, stool
discoloration making its use
unacceptable to many
children: 3 to 6 mg/kg/day threetimes-a-day dosing or single-dose
daily regimen
Ascorbic
adolescents
acid enhances
iron (qd or
: 60 mg/dose
bid)
absorption
on an empty stomach at night
26

Oral

Diagnose :
Supplementation
IDA

Oral iron
supplementati
on for 1 month

Hb
measureme
nt
No improvement in
Hb
further
evaluation : MCV,
RDW, serum
ferritin, search for
possible sources of
blood loss

Hb should
be
remeasure
d

An increase of 1
g/dL (10 g/L) or
greater
Iron
therapy
Hb has returned
to a normal level
Iron
6
therapy :
m
Iron 2 3
o
months
therapy:
STOP
27

Reasons for Poor Response to

Oral Iron
Noncompliance
Ongoing blood loss
Insufficient duration of therapy
High gastric pH
Antacids
Inhibitors of iron absorption/utilization
Lead
Aluminum intoxication (hemodialysis
patients)
Chronic inflammation
Neoplasia
Incorrect
diagnosis
Thalassemia disorder
Sideroblastic anemia
Anemia of chronic inflammation
28

Oral iron is not

tolerated

Parenteral iron

Erythrocyte
transfusion
should be used
only if the
anemia is
causing severe
cardiovascular
compromise;
hypervolemia
and cardiac
dilatation may
result from
rapid
correction of
the anemia !!

29

Parental Iron
Replacement
iron dextran, iron gluconate, iron sucrose
Indication
1. Oral iron is poorly tolerated
2. rapid replacement of iron stores is
needed
3. gastrointestinal iron absorption is
compromised
4. erythropoietin
therapy is necessary
An anaphylactic
reaction
(in renal dialysis patients)
Dose (mL) = 0.0442 x (Desired Hb
Observed Hb) x Lean body weight + (0.26 x
Lean body weight)
30

Regular
screening
Adolescents
AAP : screening all adolescents once
between ages 11 and 21 years
screening menstruating females
annually
CDC :
annual screening of adolescent
females if their risk is increased;
otherwise, anemia should be
screened for every 5 to 10 years
31

Iron Replacement in Infants

The Committee on Nutrition of the American
Academy of Pediatrics
1. Breast milk should be provided for at least 5 to 6
months.
2. Iron supplementation of 1 mg/kg/day should be
provided to infants who are exclusively fed
breast milk beyond 6 months of age.
3. Infants who are not breast-fed should be
nourished with an iron-supplemented formula (at
least 12 mg/L) until the end of the first year of
life.
4. Iron-enriched cereals should should be among
the first foods introduced with a solid diet.
5. Cows milk should be avoided during the first
year because it contains substances that chelate
32
iron and it sometimes induces occult

The evidence is clear that early

diagnosis and adequate treatment
of IDA are critical to prevention or
reversal of any negative medical or
behavioral effects.
Pediatricians must screen for this
common nutritional deficiently
actively and accurately.

33

Thank you and

have a nice day