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Definition

Anemia is the condition in which the


concentration of hemoglobin or the
red cell mass is reduced below (-2SD)

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NORMAL RED BLOOD CELL VALUES IN CHILDREN

Hemoglobin (g/dl) MCV (FL)


AGE Mean -2SD Mean -2SD

Birth (cord blood) 16,5 13,5 108 98


1-3 day (capillary) 18,5 14,5 108 95
1 week 17,5 13,5 107 88
2 week 16,5 12,5 105 86
1 month 14,0 10,0 104 85
2 month 11,5 9,0 96 77
3-6 month 11,5 9,5 91 74
0,5-2 years 12,0 10,5 78 70
2-6 years 12,5 11,5 81 75
6-12 years 13,5 11,5 86 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), Rudolph’s Fundamentals of
pediatrics, 2 nd ed. Norwalk, CT: Appleton & lange, 1998, p 441-490
MCV = mean corpuscular volume 2
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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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
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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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Suggested cut of points defining Iron status
Iron I ron Iron
depletion deficient deficient
Factor Iron sufficient non –anemic erythropoesis anemia

Children
Hb(gr/l) ≥110 ≥110 ≥110 <110
Ferritin (μg/l) ≥12 < 12 < 12 < 12
Transferrin ≥10 ≥10 <10 <10
saturation (%)
EPP (μmol/mol heme) < 100 < 100 ≥100 ≥100

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


2000,p127

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Hemogram Patterns

Severe cases
Moderate cases
  Hgb
Hgb
  Hct
Hct
  MCV
MCV
  MCH
MCH
Normocytic/ normochromic
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 body’s tissue iron stores
 Early indicator of decrease of storage iron
 Decreased only in IDA
 Reference range:
 Male: 20-250 ug/L
 Female: 10-120 ug/L
 Pediatric: 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: 60-175 ug/dL
 Female: 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
increased results
Iron

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 Serum iron


% = X 100
Saturation TIBC

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

Amount of iron Amount of preparation


Preparation Preparation (ml) in preparation (mg) to provide 3 mg (ml)

• Ferrous sulfate 5 12 1,25


oral solution
• Ferrous fumarate BP 5 45 0,3

• Ferrous succinate 5 37 0,4


elixir
• Ferrous glycine 5 25 0,6
sulfate
• Sodium iron 5 28 0,5
edetate
• Polysaccharide iron 5 100 0,15
complex

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


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Iron content of foodstuff
Food stuff Iron / 100 g % available for
absorption
Rice flour 0,9 1
Bread 2,0 5
Wheat flour 2,3 5
Cod 0,9 10
Mackerel 1,0 10
Sardines in oil 1,5 10
Oysters 7,1 10
Beef sausages 2,4
Chicken 3,0 >10
Pork chops 3,0 >10
Bacon (cooked) 3,3
Beef (rump) 2,4 >10
( kidney ) 6,5
( liver ) 12,1
*Lilleyman J. Hann I. Pediatric Hematology, 2nd ed. Churchil Livingstoon 2000,p106 36
Factors affecting iron absorption of non-heme iron
from the
Gastrointestinal tract

Increased absorption Decreased absorption

Acids Alkalis
Vitamin C Antacids
Hydrochloric acid Pancreatic secretions
Hypochlorhydria

Solutes Precipitating agents


(vegetables)
Sugars Phytates
Amino acids (meats) Phosphates
*Lilleyman J. Hann I. Pediatric Hematology, 2nd ed. Churchil 37
Livingstoon 2000,p127
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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