ANEMIA OF IRON

ABNORMAL
METABOLISM
dr Bidasari Lubis , Sp. A (K)
Bagian Ilmu Kesehatan Anak
RSU Haji Adam Malik Medan

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 Etiologic Classification & Major Diagnostic
Features of Anemia in Children

Etiologic Classification Diagnostic Features

I.Impaired red cell formation
A.Deficiency
Decreased dietary intake (e.g, excessive milk-
Iron-deficiency anemia, vegan-vit.B12 deficiency
Increased demand, e.g, growth (iron)
Hemolysis (folic acid)
Decreased absorption
Specific: intrinsic factor lack (vit. B12)
Generalized: malabsorption syndrome ( e.g,
Folic acid, iron)
Increased loss
Acute: hemorrhage (iron)
Chronic: gut bleeding (iron)

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1. Iron deficiency Hypochromic, microcytic
red cell; low MCV, low MCH, low
MCHC, high RDW, a low serum
ferritin, high FEP, guaiac positivity

2. Folate deficiency Macrocytic red cell, high

MCV, high RDW,
megaloblastic marrow,
serum & red cell folate

3. Vitamin B12 deficiency Macrocytic red cell, high

MCV, high RDW,
megaloblastic marrow, low
serum B12 gastric acidity;
Schilling test
4. Vitamin C deficiency Clinical scurvy

5. Protein deficiency Kwashiorkor

6. Vitamin B6 deficiency Hypochromic red cells,
sideroblastic bone marrow,
high serum ferritin
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 7. Thyroxine deficiency Clinical cretinism, low T4,
high TSH

B. Bone marrow failure

1.Failure of a single cell line
a. Megakaryocytes
(1) Amegakaryocytic thrombocytopenic Limb abnormalities, absent
purpura megakaryocytes
b. Red cell precursors
(1) Congenital red cell aplasia Absent red cell precusors
(Diamond-Blackfan anemia)
(2) Acquired red cell aplasia (transient Absent red cell precusors
erythroblastopenia of childhood,
TEC)
c. White cell precursors
(1) Congenital neutropenia Neutropenia, recurrent
infection

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2. Failure of all cell lines (produces aplastic
anemia characterized by pancytopenia &
cellular or hypocellular marrow)
a. Constitutional
(1) Fanconis anemia Multiple congenital
anomalies, chromosomal
breakage
(2) Familial without anomalies Familial history, no
congenital anomalies
Marked mucosal &
(3) Dyskeratosis congenita cutaneous abnormalities
No identifiable cause
b.Acquired History of exposure to
(1) Idiopathic drugs, radiation,
(2) Secondary household toxins,
infections; associated
immunologic disease

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3. Infiltration
a. De novo (e.g, leukemia) Bone marrow:
Morphology,
cytochemistry,
immunologic markers,
cytogenetics
b. Secondary (e.g, neuroblastoma, VMA, skeletal survey,
lymphoma) bone marrow

c. Dyshematopoietic anemia (decreased Evidence of systemic

Erythropoiesis, decreased iron utilization Illnes
1. Infection BUN &liver-function
2. Renal failure & hepatic disease tests
Clinical evidence
3. Disseminated malignancy Rheumatoid arthtritis
4. Connective tissue diseases

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 II Bllod loss Overt or occult-guaiac
III Hemolytic anemia
A. Corpuscular Morphology osmotic
1. Membrane defects (spherocytosis, fragility
elliptocytosis) Autohemolysis, enzyme
2. Enzymatic defects (pyrivate kinase, G6PD) assays

3. Hemoglobin defects
a. Heme Hb electrophoresis
b. Globin HbF, A2 content
(1) Qualitative (e.g, sickle cell)
(2) Quantitative (e.g, thalassemia)

B. Extracorpuscular Coombs test

1. Immune
a. Isoimmune
b. Autoimmune
(1) Idiopathic Coombs test, antibody
identification
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 (2) Secondary
Decreased C3, C4, CH50;
Immunologic disorder (e.g, lupus)
positive ANA
One cell line (e.g, red cells)
Anemia: Coombs positive
Multiple cell line (e.g, white blood
Neutropenia
cells, platelets)
immunotropenia,
thrombocytopenia-ITP
2. Nonimmune (idiopathic, secondary)

Cause of Iron-Deficiency Anemia

I. Deficiency intake
Dietary (milk 0.75 mg iron/L)
II. Increased demand
Growth (low birth weight, prematurity, low-birth-weight twins
or multiple births, adolescence, pregnancy),
cyanotic heart disease

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III. Blood loss
A. Perinatal
1. Placental
a. Transplacental bleeding inti maternal
circulation
b. Retroplacental
(e.g, premature placental separation)
c. Intraplacental
d. Fetal blood loss at or before birth
(e.g, placenta previa)
e. Fetofetal bleeding

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 2. Umbilicus
a. Ruptured umbilical cord (e.g, vasa previa)
b. Inadequate cord tying
c. Postexchange transfusion
B. Postnatal
1. Gut
a. Primary iron-deficiency anemia
b. Hypersensitivity to whole cows milk
c. Anatomic gut lesions
d. Gastritis
e. Intestinal parasites
f. Henoch-Schonlein purpura

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 2. Gallbladder : hemocholecyst
3. Lung : pulmonary hemosiderosis, Goodpastures syndrome,
defective iron mobilization with IgA deficiency
4. Nose : recurrent epistaxis
5. Uterus : menstrual loss
6. Heart : intracardiac myxomata, valvular prostheses or patches
7. Kidney : traumatic hemolytic anemia, hematuria,
nephrotic syndrome (urinary loss of transferrin),
hemosiderinurias-chronic intravascular hemolysis
(e.g, paroxysmal nocturnal hemoglobinuria,
paroxysmal cold hemoglobinuria march hemoglobinuria)
8. Extracorporeal : hemodialysis, trauma
IV. Impaired absorption
Malabsorption syndrome, celiac disease,
severe prolonged diarrhea, postgastrectomy,
inflammatory bowel disease
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Anemia Of Abnormal Iron
Metabolism

Most frequent types of anemias

Iron deficiency anemia (IDA)
Anemia of chronic disease

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Characteristics

Etiology related to abnormalities

associated with iron metabolism
Maturation disorder
Reticulocyte production index (RPI) <2.0
Predominantly microcytic RBCs
Variable red blood cell distribution width
(RDW)

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Demographics & Etiologies
IDA

Children
Increased iron need
Diet
Pregnancy: Increased need
Loss during lactation

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Demographics & Etiologies
IDA

Diet
Inadequate intake
Achlorhydria
Gastric acid required for proper absorption of iron
Needed to convert Fe+3 (non-absorbable form) to
Fe+2 (absorbable form)
Malabsorption Decrease in absorptive
surfaces of the intestine

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Demographics & Etiologies
IDA

Men/postmenopausal women: Chronic

blood loss
Gastrointestinal bleeding
Esophageal varices
Peptic ulcer
Gastrointestinal neoplasm
Hemorrhoids
Blood donation
Chronic intravascular hemolytic disease
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Pathophysiology: Natural Course
Iron repletion: Normal iron stores
Iron depletion: Increased utilization of
storage iron
Iron deficiency
Absent bone marrow iron stores
No peripheral anemia
IDA
Absent bone marrow iron stores and
Peripheral anemia and associated
morphology
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Hemogram Patterns

Moderate cases Severe cases

Hgb Hgb
Hct Hct
MCV MCV
MCH MCH
Normocytic/ Microcytic/hypochromic
normochromic Poikilocytosis

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Primary Laboratory Investigation

RBC morphology
Anisocytosis
Poikilocytosis
Microcytosis
Hypochromia

>1/3 Total Dia.

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Iron Deficiency
Morphology

Moderate Severe

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Tissue Effects of Iron Deficiency

I. Gastrointestinal tract
A. Anorexia common & early
1. Increased proportion of low-weight percentiles
2. Depression of growth
B. Pica-pagophagia (ice), geophagia (sand)
C. Atropic glossitis
D. Dysphagia
E. Esophageal webs (Kelly-Paterson syndrome)
F. Reduced gastric acidity
G. Leaky gut syndrome
1. Guaiac-positive stool, isolated
2. Exudative enteropathy: gastrointestinal loss of protein,
albumin, immunoglobulins, coopper, calcium, red cells
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 H. Malabsorption syndrome
1. Iron only
2. Generalized malabsorption: xylose, fat, vit.A, duodenojejunal
mucosal atrophy
I. Beeturia
J. Decrease cytochrome oxidase activity & succinic dehydrogenese
K. Decrease disaccharidases
L. Increased absorption of lead & cadmium
M. Increased intestinal permeability index
II. Central nervous system
A. Irritability
B. Fatigue
C. Conduct disorders
D.Lower mental & motor developmental test score on the Bayley Scale,
which may be long-lasting

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E. Increased tolerance to digitalis
IV. Musculoskeletal system
A. deficiency of myoglobin & cytochrome C
B. Impaired performance of a brief intense exercise task
C. Decreased physical performance in prolonged endurance work
D. Rapid development of tissue lactic acidosis in exercise &
a decrease in mitocondrial -glycerophosphate oxidase activity
E. Radiographic changes in bone-widening of diploeic spaces
F. Adverse effect on fracture healing
V. Immunologic system
There is conflicting information as to the effect on the immunologic
system of iron deficiency anemia
A. Evidence of increased propensity to infection
1. Clinical
a. Reduction of acute illness in iron-deficient children
by iron treatment & improved rate of recovery
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 b. Increased frequency of respiratory infection in iron deficiency
2. Laboratory
a. Impaired leukocyte transformation
b. Impaired granulocyte killing & nitroblue tetrazolium (NBT) reduction
by granulocytes
c. Decreased myeloperoxidase in leukocytes & small intestine
d. Decrease cutaneus htpersensitivity.
e. Increased susceptibility tio infection in iron-deficient animals
B. Evidence of decreased propensity for infection
1. Clinical
a. Lower frequency of bacterial infection
b. Increased frequency of infection in iron overload
2. Laboratory
a.Transferrin inhibition of bacterial growth by binding iron so that no free
iron is available for growth of microorganisms
b. Enhancement of growth of nonpathogenic bacteria by iron
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VI. Cellular changes
A. Red cells
1. Infective erythropoiesis
2. Decreased red cell survival
3. Increased autohemolysis
4. Increased red cells rigidity
5. Increased susceptibility to sulfhydryl inhibitors
6. Decreased heme production
7. Decreased globin & - chain synthesis
8. Precipitation of -globin monomers to cell membrane
9. Decreased glutathione peroxidase & catalase activity
a. Inefficient H2O2 detoxification
b. Greater susceptibility to H2O2 hemolysis
c. Oxidative damage to cell membrane
d. Increased cellular rigidity
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 10. Increased rate of glycolysis: glucose 6-phosphatase dehydrogenase
6 - phosphogluconate dehydrogenase, 2.3-diphosphoglycerate
(2.3-DPG), & glutathione
11. Increased in NADH-methemoglobin reductase
12. Increased in erythrocyte glutamic oxaloacetic transaminase (EGOT)
13. Increased in free erythrocyte protoporphyrin
14. Impairment of DNA & RNA synthesis in bone marrow cells
B. Other tissues
1. Reduction in heme-containing enzymes (cytochrome C, cytochrome oxidase
2. Reduction in iron-dependent enzymes (succinic dehydrogenase aconitase)
3. Reduction in monoamine oxidase (MAO)
4. Increased excretion of urinary norepinephrine
5. Reduction in tyrosine hydroxylase (enzyme converting tyrosine to
dihydroxyphenylalanine)
6. Alterations in cellular growth, DNA, RNA, & protein
7. Persistent deficiency of brain iron following short-term deprivation
8. Reduction in plasma zinc
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Diagnosis:
1. Hemoglobin : Hemoglobin is below
2. Red cell indices : MCV, MCH, & MCHC are lower
RDW is one of the best screening tests for iron deficiency
3. Blood smear:red cells are hypochromic & microcytic,
generally occuring only when Hb falls below 10 g/dl
4. Reticulocyte count: usually normal
5. Platelet count: the platelet count varies from
thrombocytopenia to thrombocytosis
6. Free erythrocyte protoporphyrin: FEP level is elevated
7. Serum ferritin : A concentration of less than 12 ng/ml
suggest irondeficiency
8. Serum iron & iron saturation percentage
9. Prussian Blue (iron) stain
10. Serum transferrin receptor
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Prussian Blue (Iron) Stain

Assessment of storage iron in the bone

marrow
Blue-green stain indicates presence of
storage iron
Storage iron mostly confined to
macrophages
Small percent in sideroblasts
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BMP IRON DEFICIENCY
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Prussian Blue (Iron) Stain

Considerations
Positive control films must be used
Rinsing with tap water may cause
overstaining/false positives

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BMP IRON DEFICIENCY PRUSSIAN BLUE
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Treatment:
Nutritional Counseling

1.Maintain breast feeding at least 6 months, if possibl

2.Use an iron-fortified (6-12 mg/l) infant formula until
1 year of age (formula is preferred to whole cows milk).
Restrict milk to 1 pint/day
3.Use iron-fortified cereal from 6 months to 1 year
4.Use evaporated milk or soy-based formula when iron
deficiency is caused by hypersensitivity to cows milk
5. Provide suplemental iron for low birth weight infant
a. Infants 1.5 2.0 Kg : 2mg/kg/day suplemental iron
b. Infants 1.0 -1.5 Kg : 3mg/kg/day suplemental iron
c. Infants < 1.0 Kg : 4mg/kg/day suplemental iron
6.Facilitators of iron absorption such vit.C-rich food, meat, fish,
& poultry should be included in the diet, & inhibitors of
iron absorption such as tea, phosphate, & phytates common
in vegetarian diets should be eliminated

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Oral Iron Medication

1.Product: ferrous iron (e.g, ferrous gluconate, ferrous ascorbate,

ferrous lactate, ferrous succinate, ferrous fumarate,
ferrous glycine sulafate) is effective.

2. Dose: 1.5 2.0 mg/kg elemental iron three times daily.

Older children : ferous sulfate (0.2g) or ferrous gluconate (0.3 g)
given three times daily to provide 100-200 mg elemental iron

3. Duration: 6 8 weeks after Hb level is restored to normal

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Parenteral Therapy

Iron-dextran complex I.M (Imferon )

Indications:
1. Noncompliance with oral administration of iron
2. Severe bowel disease
(e.g inflammatory bowel disease) ;
use of oral iron might aggravate
the underlying disease of the gut

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