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Iron Deficiency Anemia

Definition
Anemia is the condition in which the
concentration of hemoglobin or the
red cell mass is reduced below (-2SD)

NORMAL RED BLOOD CELL VALUES IN CHILDREN

Hemoglobin (g/dl)
AGE

Mean

-2SD

MCV (FL)
Mean

-2SD

Birth (cord blood) 16,5

13,5

108

98

1-3 day (capillary)18,5


1 week 17,5
13,5
2 week 16,5
12,5
1 month 14,0
10,0
2 month 11,5
9,0
3-6 month
11,5
0,5-2 years
12,0
2-6 years
12,5
6-12 years
13,5

14,5
107
105
104
96
9,5
10,5
11,5
11,5

108
88
86
85
77
91
78
81
86

95

74
70
75
77

Compiled from several sources; the mean 2 SD can be expected to include 95% of the
observations in normal population. In Rudolph AM, Kamei RK (eds), Rudolphs Fundamentals of
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pediatrics, 2 nd ed. Norwalk, CT: Appleton & lange, 1998, p 441-490
MCV = mean corpuscular volume

Anemia Of Abnormal Iron


Metabolism
Most frequent types of anemias
Iron deficiency anemia (IDA)
Anemia of chronic disease

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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Etiologic classification
Impaired red cell formation
Deficiency
Bone marrow failure
Failure of a single cell line
Failure of all cell lines
Infiltration

Dyshematopoietic anemia

Infection
Renal failure and hepatic disease
Disseminate malignancy
Connective tissue diseases

Blood loss
Hemolytic anemia
Corpucular
Extra corpuscular

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

Suggested cut of points defining Iron status


Factor

Iron sufficient

Children
Hb(gr/l)
Ferritin (g/l)
Transferrin
saturation (%)
EPP (mol/mol heme)

Iron
depletion
non anemic

I ron
deficient
erythropoesis

Iron
deficient
anemia

110
12

110
< 12

110
< 12

<110
< 12

10

10

<10

<10

< 100

< 100

100

100

*Lilleyman J. Hann I. Pediatric Hematology, 2nd ed. Churchil Livingstoon


2000,p127

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Hemogram Patterns
Moderate cases
Hgb
Hct
MCV
MCH
Normocytic/
normochromic

Severe cases
Hgb
Hct
MCV
MCH
Microcytic/hypochromic
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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Clinical Signs & Symptoms


Presenting symptoms
Generic to other anemias
Symptoms manifest late in course because
of gradual onset
Symptoms may be associated with
underlying primary disease
Blood loss
Pica
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Clinical Signs & Symptoms


Physical findings
Epithelial changes
Stomatitis
Glossitis
Gastritis
Koilonychia: Flattened or spoon-shaped
fingernails

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Secondary Laboratory
Investigation

Serum ferritin
Serum iron
Iron binding capacity
Prussian Blue (iron) stain

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Serum Ferritin

Storage form of iron


Measures bodys tissue iron stores
Early indicator of decrease of storage iron
Decreased only in IDA
Reference range:
Male:
Female:
Pediatric:

20-250 ug/L
10-120 ug/L
See below
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Serum Ferritin
Pediatric reference range:
1 month:
200-600 ug/L
1-6 months: Comparable to adult males
Childhood:
Generally low ferritin levels

Considerations
Elevated during acute inflammatory
processes
No diurnal variation
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Serum Ferritin
Considerations, continued
Not changed by exogenous iron
ingestion

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Serum Iron
Measurement of transferrin-bound iron
Serum iron:
Male:
Female:

60-175 ug/dL
50-170 ug/dL

Considerations
Hemolysis may significantly affect test results
Chelating anticoagulants may lead to falsely
decreased results
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Serum Iron
Considerations:
Diurnal variation: AM Peak, PM Trough
Fasting specimen
Iron-containing medication can lead to falsely

Iron

increased results

12 AM

12 PM

12 AM

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Total Iron
Binding Capacity
Measures the potential binding capacity of
circulating transferrin
With serum Fe used to determine
saturation
Total iron binding capacity: Reference
range 250-450 ug/dL
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Total Iron Binding


Capacity
Considerations
No diurnal variation
Same specimen requirements as
serum Fe

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Transferrin Saturation
Transferrin
%
Saturation

Serum iron
TIBC

X 100

Percent transferrin saturation: Reference range 20-55%

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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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BMP IRON DEFICIENCY PRUSSIAN BLUE

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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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Assessment of Bone Marrow


Sideroblasts
Nucleated RBCs that contain stainable
iron (ferritin)
Type I
Up to four granules/cell
Random cytoplasmic distribution
Seen in approximately 25-50% of NRBCs of
normal individuals

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Sideroblasts
Type II
>6 granules/cell
Random cytoplasmic distribution

Type III
Larger granules
Arranged in ring around the nucleus
>15% indicate sideroblastic anemia

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Effects of Treatment
Treatment consists of:
Iron supplementation and/or
Controlling underlying disease

Laboratory effects
Increased reticulocyte count within days
(RPI>3)
Peak reticulocyte count in 7-12 days
Hemoglobin returns to normal in
approximately 2 months
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Treatment
Laboratory effects, Continued
Peripheral RBC dimorphism appears as
hemoglobin level returns to normal
Changes in RBC histogram
Return of measures of iron store status to
normal levels

Ineffective treatment/complications
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Oral Iron
Standard oral treatment of iron deficiency is 3 mg iron/kg
body weight/day , max 180 mg daily
Three milligrams of iron is provided by :
15 mg ferrous sulfate
9 mg ferrous fumarate
26 mg ferrous gluconate
9 mg ferrous succinate
17 mg ferrous glycine sulfate
21 mg sodium iron edetate
9 mg ferrous sulfate dried
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Liquid preparations of iron

Preparation

Preparation (ml)

Amount of iron
in preparation (mg)

Amount of preparation
to provide 3 mg (ml)

Ferrous sulfate
oral solution
Ferrous fumarate BP

12

1,25

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0,3

Ferrous succinate
elixir
Ferrous glycine
sulfate
Sodium iron
edetate
Polysaccharide iron
complex

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0,4

25

0,6

28

0,5

100

0,15

**Lilleyman J. Hann I. Pediatric Hematology, 2nd ed. Churchil Livingstoon 2000,p133

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Iron content of foodstuff


Food stuff
absorption
Rice flour
Bread
Wheat flour
Cod
Mackerel
Sardines in oil
Oysters

Iron / 100 g
0,9
2,0
2,3
0,9
1,0
1,5
7,1

% available for
1
5
5
10
10
10
10

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Factors affecting iron absorption of non-heme iron


from the
Gastrointestinal tract
Increased absorption
Acids
Vitamin C
Hydrochloric acid
Hypochlorhydria
Solutes
Sugars
Amino acids (meats)

Decreased absorption
Alkalis
Antacids
Pancreatic secretions
Precipitating agents (vegetables)
Phytates
Phosphates

*Lilleyman J. Hann I. Pediatric Hematology, 2nd ed. Churchil Livingstoon 2000,p127

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Food fortification choice of food vehicle


Step in developing an iron fortification
strategy
Determine the iron status of the population
Choose an appropriate iron compound and
food vehicle
Establish the acceptability and stability of the
fortified vehicle
Assess the bioavailability of iron from the
vehicle in the
Carry out a controlled field trial
Implement a regional or national fortification
program

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Other Disorders
Anemia of chronic disease
Hemochromatosis/iron overload

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Summary
Characteristics of anemias of abnormal
iron metabolism
Hemogram patterns
Natural course of IDA
Secondary laboratory investigation
Sideroblasts
Effects of treatment
Other Disorders
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