Iron Deficiency Anemia

FACULTY OF MEDICINE
UNIVERSITY OF BRAWIJAYA MALANG

Clinical Competencies
Be able to describe:
- the causes of iron deficiency anemia
- the pathogenesis and pathophysiology of iron
deficiency anemia
- the stages in development of iron deficiency anemia
- the principal management of iron deficiency anemia
Be able to diagnose iron deficiency anemia based on
clinical features and laboratory findings

Faculty of Medicine
University of Brawijaya

Introduction
Iron deficiency is defined as a decreased total iron body
content.
Iron deficiency is the most prevalent single deficiency
state on a worldwide.
If iron deficiency is sufficiently severe to diminish
erythropoiesis of anemia iron deficiency anemia.
Diminished the capability of individuals: to perform
physical labor, growth and development, academic
achievement of children.

Faculty of Medicine
University of Brawijaya

Iron deficiency anemia 2001

underfives children in Indonesia

Household Survey, 2001

Untoro R. Peningkatan Kualitas Hidup Anak Melalui Pencegahan Anemia Gizi Besi.
Disajikan pada Kampanye Anti Anemia 2006-2008. Depkes, Jakarta, 1 Maret 2007

Etiologic factors in iron deficiency anemia :

1. Negative iron balance
a. Decreased iron intake
- Inadequate diet
- Impaired absorption
b. Increased iron loss blood loss
- Gastrointestinal blood loss : epistaxis, varices,
gastritis, ulcer, etc
- Genitourinary blood loss : menorrhagia, chronic
infections, cancer
- Other blood loss : trauma, excessive phlebotomy,
etc.
c. Increased requirements
- Infancy
- Pregnancy
- Lactation

Etiologic factors in iron deficiency anemia

(contd) :
2. Inadequate presentation to erythroid
precursors
a. Atransferrinemia
b. Antitransferrin receptor antibodies
3. Abnormal iron balance
a. Aceruloplasminemia
b. Autosomal-dominant hemochromatosis due
to mutations in ferroportin

Iron metabolisms
Body iron distribution and transport
Iron absorption
Iron requirement

Andrew NC. Medical Progress: Disorders of Iron Metabolism. N Engl J Med 1999;
341: 1986-95
th
Hoffbrand AV, et al. Essential Hematology. 4 . London:Blackwell Science.2001

Body iron
distribution

Iron transport across the intestinal

epithelium

Andrew NC. Medical Progress: Disorders of Iron Metabolism. N Engl J Med 1999; 341:
1986-95

The transferrin cycles

Andrew NC. Medical Progress: Disorders of Iron Metabolism. N Engl J Med 1999; 341:
1986-95

Iron absorption
Factors favouring absorption
Hem iron
Ferrous form (Fe2+)
Acids (HCl, vit. C)
Solubilizing agents (sugars,
aminoacids)
Iron deficiency
Increased erythropoiesis
Pregnancy
Hereditary hemochromatosis
Increased expression of DMT-1
&
ferroportin in duodenal
enterocytes

Factors reducing absorption

Inorganic iron
Ferric form (Fe3+)
Alkalis antacids, pancreatic
secretions
Precipitating agents phytates,
phosphates
Iron excess
Decreased erythropoiesis
Infections
Tea
Decreased expression of DMT-1 &
ferroportin in duodenal
enterocytes

Hoffbrand AV, et al. Essential Hematology. 4th. London:Blackwell Science.2001

Iron requirements
Estimated daily iron requirements
In children (average):
- Urine, sweat, feces : 0.5 mg/day
- Growth
: 0.6 mg/day
- Total
: 1.1 mg/day

In female (age 12-15 yrs):

- Urine, sweat, feces : 0.5-1 mg/day
- Menses
: 0.5-1 mg/day
- Growth
: 0.6 mg/day
- Total
: 1.6-2.6 mg/day
Hoffbrand AV, et al. Essential Hematology. 4th. London:Blackwell Science.2001

PATHOGENESIS OF IDA
Three pathogenetic and pathophysiologic factors
are implicated in the anemia of iron deficiency :
1. Impaired hemoglobin synthesis, a
concequence of reduced iron supply.
2. A generalized defect in cellular proliferation.
3. Reduced erythrocyte survival, particularly
when the anemia is severe.

Staging of Iron Deficiency

Staging I
Iron depletion (without anemia)
Staging II
Iron deficiency (without anemia)
Staging III
Iron deficiency (with anemia)
Iron deficiency anemia

Faculty of Medicine
University of Brawijaya

Raspati H dkk. Buku Ajar Hemato-onkologi anak 2005.

CLINICAL STAGES IN DEVELOPMENT OF

IRON DEFICIENCY ANEMIA
Stage I
Prelatent/
Iron Depletion

Stage II
Latent/
Iron Deficiency

Stage III
Iron Deficiency
Anemia

Symptoms

Fatique, malaise in some patients

Pallor, pica,
epithelial changes

Hemoglobin levels

Normal

Normal

Decreased

Mean corpuscular volume

Normal

Normal

Decreased

Reticulocyte Hb content

Normal

Decreased

Decreased

Serum iron

Normal

< 60 ug/dl

< 40 g/dl

Total iron binding capacity

360-390 g/dl

> 390 g/dl

> 410 d/dl

Transferrin saturation

Normal

< 16%

< 16%

Serum ferritin

< 20 g/L

< 12 g/L

< 12 g/L

Free erythrocyte
protoporphyrin,
zinc protoporphyrin

Normal

Increased

Increased

Bone marrow iron

Decreased

Absent

Absent

Diagnosis
History findings :
- onset & severity of anemia, age
- parasitism, blood loss (acute or chronic)
- inadequate diet (quantity & quality)
- poor absorption
- increased requirements

Clinical features :
symptoms & signs (general & specific)

Laboratory findings :
hematologic & biochemical markers

CLINICAL FEATURES OF IDA

Patients with anemia may present with fatique,
pallor, vertigo, dyspnea, cold intolerance & lethargy
Symptoms unique to the IDA patient are :
- pica (an abnormal craving for unusual
substances
such as dirt, ice, or clay)
- cheilitis (inflammation around the lips)
- koilonychias (spooning of the nail beds)
IDA in infants may result in developmental delays and
behavioral disturbances.
IDA in the 1st two trimesters pregnant women may
lead to an increase in preterm delivery and an
increase in delivering a low-birth-weight baby.

LABORATORY FINDINGS OF IDA

Hb level < normal varies by sex and age
MCV and MCHC will be markedly < normal
RDW may be mildly
The reticulocyte count will be low
Peripheral blood smear : hypochromic microcytic
Test to assess a patients iron status include :
-

serum iron (SI) normal 50-150 g/L

TIBC normal 250-540 g/L
transferrin saturation normal 20-50%
serum ferritin normal : 20-250 g/L
10-120 g/L

 Koilonikia

LABORATORY FINDINGS OF IDA..(contd)

Tests are useful to establish the etiology of IDA
- stool examination
- test to detect blood loss : Benzidin test,
radiolabelled
- test to assess hemoglobinuria
hemosiderinuria
- Hb electrophoresis to establish thalassemia

&

MANAGEMENT OF IDA
TREATMENT
1. Medication : elemental iron
In adult : 325 mg (60 mg Fe) orally 3x/day
In child : 3-6 mg/kg/day orally divided in 1-3 dosis
2. Dietetic therapy
3. Surgical treatment : to stop bleeding and correct
the underlying defect either neoplastic or nonneoplastic disease of GIT, GUT, uterus, and lungs
4. Consultation : department of surgery, GE, etc
5. Activity : restriction of activity is usually not
required; patients with moderately severe IDA
and significant cardiopulmonary disease should
limit their activities

Treatment
Elemental Fe
- Do: 3-6 mg/kgBW/d (2-3 dosages)
- It may take up to 2 mo after hemoglobin has
been corrected
- Adverse effects : GI tract upset
to reduce the adverse reactions :
- take the medicine after meal
- slow released preparation
- take a dosage then increase gradually
Treat the etiology
Lanzkowsky P. 1995. p. 35-50.
Glader B. Nelson Textbook of pediatrics. 17th ed.; 2004. p. 1614-6.
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:1423-38.
Killip S, et al. Am Fam Physician 2007;75:671-8.
Segel GB, et al. Pediatr Rev 2002;23:75-84.
Grantham-McGregor S & Ani C. J Nutr 2001;131:649S-68S.

Iron preparation
Preparation

Available strength

Elemental Fe

Ferrous fumarate

300 mg/cap

99 mg/cap

Ferrous gluconate

300 mg/tab

35 mg/tab

300-325 mg/tab

60-65 mg/tab

Ferrous sulphate, slow released

160 mg/tab

65 mg/tab

Polysaccharide-iron complex

150 mg/tab

150 mg/cap

Ferrous fumarate

60 mg/ml

20 mg/ml

Ferrous sulphate

Drops : 75 mg/ml
Syrup : 30 mg/ml

Drops : 15 mg/ml
Syrup : 6 mg/ml

Iron dextran

--

50 mg/ml

Sodium ferric gluconate

--

12.5 mg/ml

Iron sucrose

--

20 mg/ml

Tablets/capsules

Ferrous sulphate

Oral liquid suspensions

Parenteral

http://www.freece.com/FreeCe/Article.asp?dbArticleID=105.

Response to iron therapy in

iron-deficiency anemia

Lanzkowsky P. 1995. p. 35-50.

Glader B. In: Nelson Textbook of pediatrics. 17th ed.; 2004. p.
1614-6.
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:1423-38.
Killip S, et al. Am Fam Physician 2007;75:671-8.
Segel GB, et al. Pediatr Rev 2002;23:75-84.

Transfusion
Indication :
If hemoglobin levels < 4 g/dL
Lanzkowsky P. 1995. p. 35-50.
Glader B. Nelson Textbook of pediatrics. 17th ed.; 2004. p.
1614-6.

Dept. of Child Health Dr. Saiful Anwar Hospital:

Hb < 7 /dL g/dL
Hb > 7 g/dL, with cardiorespiratory disturbances,
severe infection, dehydration, surgical
procedures

Diet
Milk : 24 oz/day
Iron rich food (fish, liver, meat) rather than rice,
spinach, wheat, soybean
absorption: tanin, calsium, phytates
absorption: vitamin C, HCl, amino acid,
fructosa,
meat
Lanzkowsky P. 1995. p. 35-50.
Glader B. Nelson Textbook of pediatrics. 17th ed.; 2004. p.
1614-6.
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:142338.

Parenteral iron therapy

If not successful with oral iron preparation
parenteral therapy
Indication:
- Severe bowel disease
- Genuine intolerance of oral iron
- Chronic hemorrhage
Adverse reaction :
- Mild : fever, headache, pruritus, nausea
- Life threatening : anaphylaxis shock
Lanzkowsky P. 1995. p. 35-50.
Glader B. Nelson Textbook of pediatrics. 17th ed.; 2004. p.
1614-6.
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:142338.
Killip S, et al. Am Fam Physician 2007;75:671-8.

Prevention
Primary prevention
Exclusive breastfeeding
- The absorption of iron from breast milk is
higher than that from whole cows milk (50% vs
10%)
- Iron-fortified cows milk : 4%
Milk consumption : 24 oz/day (other: 16 oz/day)

Lanzkowsky P. 1995. p. 35-50

Glader B. Nelson Textbook of pediatrics. 17th ed.; 2004. p.
1614-6
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:1423-38
Killip S, et al. Am Fam Physician 2007;75:671-8
Segel GB, et al. Pediatr Rev 2002;23:75-84
Oski FA. N Engl J Med 1993;329:190-3

Primary prevention..

Allen LH. J Nutr 2002;132:813S-9S

Lanzkowsky P. 1995. p. 35-50
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:1423-38
Oski FA. N Engl J Med 1993;329:190-3

Secondary prevention
SCREENING
CBC, serum ferritin and transferrin
saturation

First year of life

Diet :
- Cows milk consumption
- Low iron-fortified formula
- Exclusive breastfeeding without
Fe supplement
Prenatal/perinatal
- Anemia during pregnancy
- Low birth weight
- Prematurity
- Gemelli
Socioeconomic
- Low socioeconomic
- Imigrant from the developing countries
- High growth rate

Aterm: age 9-12

mo
Prematur/LBW or
gemelli: age 6 mo

Secondary prevention.
Age 1-3 years
History of iron deficiency anemia (+)
Milk consumption > 24 oz/day
Poor intake of iron and vitamin C
Imigrant from the developing countries

age 15-18 months and 24 months

Sandoval et al. Hematol Oncol Clin N Am 2004;18:1423-38.

Killip et al. Am Fam Physician 2007;75:671-8.
Brugnara. Clin Chemistry 2003;49:1573-8.

Lack of response to iron therapy

Inappropriate dosage
Ineffective iron preparation
Did not solve the etiology (e.g. ongoing blood
loss)
Incorrect diagnosis
Poor compliance

Lanzkowsky P. 1995. p. 35-50

Glader B. Nelson Textbook of pediatrics. 17th ed.; 2004. p.
1614-6
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:1423-38
Killip S, et al. Am Fam Physician 2007;75:671-8
Segel GB, et al. Pediatr Rev 2002;23:75-84

THANK YOU

Etiology of iron deficiency

Less 1 year
Low iron storage (LBW or gemelli)
Lack of iron supplements in exclusively breastfed infants beyond 6 months of age
Unfortified milk formula
Age 1-2 year
Milkaholics
Increased iron needs due to chronic infection
Malabsorption
Blood loss >> eg. parasitic infection and
Meckels diverticulum

Etiology
Age 2-5 year
Poor intake of iron-rich food
Increased iron needs due to chronic infection
Blood loss >> eg. Parasitic infection and
Meckels diverticulum
Age 5 year adolescence
Blood loss >> eg. Parasitic infection or
polyposis
Adolescence adult
Woman : eg. menorrhagia
Lanzkowsky P. 1995. p. 35-50.
Glader B. In: Nelson Textbook of pediatrics. 17th ed.; 2004. p. 1614-6.
Sandoval C, et al. Hematol Oncol Clin N Am 2004;18:1423-38.
Killip S, et al. Am Fam Physician 2007;75:671-8.
Segel GB, et al. Pediatr Rev 2002;23:75-84.

UNDERLYING CAUSES
Low food supply
Erroneous feeding
practices
Low socio-economic status
Low intake of available iron
Unsuitable meal
composition
excess of inhibitors

IMMEDIATE CAUSES
Inadequate diet

Poor absorption

Growth
Pregnancy & Lactation

Increased
requirements

Acute bleeding
Chronic blood loss
Poor sanitation &
parasitism

Blood loss

Inadequate health services

Infection

Iron
deficiency

Figure 5. The Underlying and Immediate Causes of Iron Deficiency

Source : Florentina RF, et al (1984)

Table 4. Recommendations to Prevent and Control Iron Deficiency in

the US
For infants (0 to 12 months) and children (1 to 5 years)
Encourage breastfeeding or
Iron-fortified formula
Serve one serving of fruits, vegetables, juice by 6 months
Screen children for anemia every 6 months
School-age children (5 to 12 years) and adolescent boys (12 to 18 years)
Screen only those with history of IDA or low iron intake groups
Adolescent girls (12 to 18 years) and nonpregnant women of childbearing age
Encourage intake of iron-rich food and foods that increase iron absorption
Screen nonpregnant women every 5 to 10 years through childbearing
years
Pregnant women
Start oral doses of iron at first prenatal visit
Screen for anemia at first prenatal visit
If hemoglobin is _9 g/dL, provide further medical attention
Postpartum women
Risk factors include continued anemia, excessive blood loss & multiple
births
Males older than 18 years/postmenopausal women
No routine screening is recommended

Controversies
A single vs 3-times-daily dose iron
supplementation
resulted in a similar rate of successful
treatment
Zlotkin et al. Pediatrics 2001;108:613-6
of anemia (Hb & ferritin) (p= 0,25 and p=0,99)
Iron supplementation 1-2 weekly vs daily
- The increases in Hb concentration were
comparable
- Improvement of cognitive function
- Cost effective
- No or fewer side-effect
Sungthong et al. J Nutr 2004;134:2349-54
Siddiqui et al. J Trop Pediatr 2004;50:276-8
Awasthi et al. J Trop Pediatr 2005;51:67-71

Controversies..
Several micronutrients can improve the
hemoglobin response to iron.
Iron absorption may be inhibited by nutrients
such calsium, magnesium and zinc.
Allen LH. J Nutr 2002;132:813S-9S

Multivitamins with iron was not effective in

preventing iron deficiency
Geltzman et al. Pediatrics 2004;114:86 93.