Anemia

Hematology-Oncology Division Child Health

Departement ,Medical School University of
Sumatera Utara

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 Anemia

Definition :

Reduction in hemoglobin concentration ,

hematocrit or number of red cells per cubic
millimeter . The lower limit of the normal
range is two standard deviations below the
mean for age and sex for normal population

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 Table 1. Normal red blood cell values in children

Hemoglobin (g/dl) MCV (fl)

AGE Mean - 2 SD Mean - 2 SD

Birth (cord blood) 16.5 13.5 108 98
1-3 days (capillary) 18.5 14.5 108 95
1 week 17.5 13.5 107 88
2 weeks 16.5 12.5 105 86
1 month 14.0 10.0 104 85
2 months 11.5 9.0 96 77
3-6 months 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
12-18 years, female 14.0 12.0 90 78
12-18 years, male 14.5 13.0 88 78
18-49 years, female 14.0 12.0 90 80
18-49 years, male 15.5 13.5 90 80

Hasting, C. Anemia , In: Hematology/oncology handbook,

HIS2002 ;3
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Level Hemoglobin and Hematocrit
( WHO 2001 )

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 Classification of Anemia

Screening Hb CBC:
MCV- MCH
Peripheral blood
smear
Microcytic, Reticuloyte index
Normocytic,
hypochromic
normochromic Macrocytic
MCV <80 fL
MCV 80-95 fL MCV >95 fL
MCH <27 pg
MCH 27 pg
Megaloblastic:
Iron deficiency anemia Hemolytic anemia vitamin B12 deficiency
Anemia chronic disease or folat
Thalassemia
Anemia due to bleeding Non-megaloblastic:
Anemia chronic alcohol, liver disease,
disease Renal disease myelodysplasia
Lead poisoning Mixed deficiency Aplastic anemia
Bone marrow failure
Sideroblastic anemia

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 Asses degree of Anemia

Mild Moderate Severe

(Hb > 10 g/dl) (Hb 7-10 g/dl) (Hb <7 g/dl)

History and physical examamination History, physical examination

Compatible with iron deficiency Iron studies

or (Hb electrophoresis)
Trial of oral iron 4-6 mg/kg/day Iron studies Family studies
Deficient
Dietary counselling (FEP, Fe/TIBC, %
Not transferin sat.)
Reticulocyte count at 1 week Hospitalization
Improved
Improved Suggestive smear
Consider : Transfusion
Continue oral Fe Reticulocyte count
Iv or oral iron (if indicated)
3-6 months Stool guaiac

Blood loss (urinalysis, stool guaiac, Meckels Severe iron deficiency

scan) Hemogloinopathy/thalassemia
Red cell aplasia
Hemolysis (Coomb test, perpheral smear) (Hb electrophoresis, family
studies) Malignancies
Hemoglobinopathy/thalassemia
Lead toxicity Infection
Hb electrophoresis
Hemolytic anemia with illness/infection
Family studies
Thalassemia
Lead poisoning
Thalassemia mayor, Hb H diseases
Iron studies, Iron malabsorption
Hemoglobinopathies
Oral iron challenge, consider parenteral iron
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Hasting, C. Anemia , In: Hematology/oncology handbook, 2002 ; 2
 Microcytic Anemia
1. Iron Deficiency Anemia ( IDA)
2. Thalassemia minor/trait
3. Hemoglobin C and E disorders
4. Anemia of chronic Diseases (ACD )
5. Lead Poisoning
6. Sickle Thallassemias , Hemoglobin SC
Diseases
7. Rare microcytic diseases
Nelson Textbook of Pediatric,19 th ed,2011

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 IRON DEFICIENCY ANEMIA

Definition :
Anemia resulting from lack of sufficient iron for
synthesis of hemoglobin.
Prevalence :
The most common cause of anemia worlwide
An estimated 30% of the worlds population :
4.5 billion anemic
500 600 million Iron def. anemia
North American (1970) : 30 - 75% of child 1 2 years of
age
Israelli : 25% females (aged 16 - 17 yrs)
Indonesia : 25 35% (aged 5 yrs)

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 Iron cycle

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Key Functional of Iron

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ETIOLOGY
Increased physiologic requirements :
Rapid growth, menstruation, pregnancy
Decreased iron assimilation :
Iron poor diet
Iron malabsorption (pica, sprue, gastric resection)
Blood loss :
Gastrointestinal bleeding
Fetal-maternal transfusion
Hemoglobinuria
Iatrogenic
Idiopathic pulmonary hemosiderosis
Intense exercise
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 Clinical Manifestation
Pallor ,jaundice

Tachycardia
postural hypotensio

Anorexia
Angular stomatitis
Glossitis
Spoon nail

Nathan Oski,2003
Lanzkowsky P,2005
Glader B, 2007

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 CLINICAL MANIFESTATIONS

Nonhematologic consequence :
Pica :
Phagophagia (compulsive eating of ice)
Geophagia : interest in dirt consumption risk for
parasitic infestation & lead poisoning)
Ephitelial changes : Koilonychia, atrophy of lingual
papil
Exercise intolerance
Behavioral changes
Abnormal thermogenesis
Altered host response

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 LABORATORIUM FINDINGS

Red blood cells (RBCs)

Hb concentration :
Chronic iron def. red cell indices (MCV, MCH,
MCHC) : parallels with Hb concentration
Reticulocytes : slightly
Red cell morphology :
Mild iron def. hypochromic, anisocytosis
Chronic iron def. poicylocytosis (targets cells,
ovalocytes, mycrocytes & cell fragments)
RBCs survival : shortened

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Thalassemia Iron
minor Deficiency

Poikilocyt Anisocytosis
osis HIS (K-15) 2013 19
 Laboratorium
findings

Bone marrow : because hyperplasia of red cells

precursors
Platelets : to 2 4x normal
Iron metabolism :
Serum iron :
TIBC :
Transferrin sat. (ratio SI : TIBC) :
Serum ferritin : < 10 -12 g/dl
FEP (Free erythrocyte porphyrin) : > 100 g/dl
Factor VIII activity : 2 3 fold.

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DIAGNOSIS
Based of :
History
Physical examination
Laboratorium findings

Criteria of IDA by WHO :

1. Hb concentration < normal (age dependent)
2. Mean Hb concentration < 31% ( N: 32 - 35%)
3. Serum iron < 50 Ug/dl (N: 80-180 ug/dl)
4. Transferrin sat. < 15 (N: 20-50%)

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TREATMENT
Treatment of IDA is twofold :
Replenishment of body iron
Correction of the factors responsible for the
deficiency

Iron can be administered orally, IM, or IV.

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 .. Treatment

1. Oral iron therapy

Ferrous salt : adsorbed 3X better than ferric salts
Ferrous gluconate, ferrous fumarate, & ferrous
sucsinat : well adsorbed but >> expensive
Dose : 4 6 mgkg of elemental iron in three divided
doses.

2 .Parenteral iron therapy

Dose : weight (kg) x desired increment Hb (g/dl) x 2.5

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 .. Treatment

Erythropoietin
Recombinant human erythropoietin (EPO) stimulates
proliferation & differentiation of erythroid precursors
in heme synthesis.
A typical starting dose : 150 U/kg (3x a week) IV or SQ

Transfusion therapy
Children with very severe anemia (Hb < 5 g/dl)
Blood is best given : packed red cells by a modified
exchange transfusion avoid expansion of the blood
volume.
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 Factors affecting iron absorption of nonheme
iron from the gastrointestinal tract

Increased absorption
Vit C: citrus, tomatoes, potatoes,
Solutes
Sugars
meat, fish,poultry
Hydrochloric acid
Decreased absorption
Antacids
Pancreatic secretions
Hypochlorhydria
Phytates
Phosphates
Blackwell,2006
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 .. Treatment

Prevention

Encouragement of breast feeding

Use of iron - fortified infant formulas after weaning
The introduction of wholes cows milk to 1 years of age
Use of iron fortified infant cereals & ascorbid acid-rich
foods at 4 6 months
Supplemental iron for preterm infants after the first
month.

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 ..Prevention
Iron supplemental:

Exclusive breast feeding beyond 6 month :

1 mg/Kg/d
Low birth weight infants:
a. 1.5-2.0 kg : 2 mg/kg/day
b. 1.0-1.5 kg : 3 mg/kg/day
c. <1 kg : 4 mg/kg/day

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 MEGALOBLASTIC
ANEMIAS
Definition :
Abnormalities of red blood cell (RBC) morphology
and maturation.
RBC : larger than normal & have open, dispersed
nuclear chromatin, an asynchrony between the
maturation of nucleus & cytoplasm.
Etiology :
Deficiency of folic acid
95%
Deficiency Vitamin B 12
Inborn errors of metabolism (rarely)

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 Megaloblastic anemia
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32
Nucleated RBC of megaloblastic anemia

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Reticulocytes
 ETIOLOGY
Inadequate folate intake
Anemia due to decreased folate intake becomes
manifest increased vitamin requirements (pregnancy,
growth in infants & chronic hemolysis)
The normal infant daily requirements : 25 35 g/day.
Decreased folate absorption
Malabsorption due to chronic diarrheal states, diffuse
inflammatory diseases.
Previous intestinal surgery
Anticonvulsant drugs

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 FOLIC ACID DEFICIENCY

FOLATES
Abundant in many foods, including green
vegetables, fruits & animals organs.
Heat labile & water soluble
Naturally : polyglutamed form & absorbed less
efficiently than the monoglutamate species (folic
acid).
Folic acid : adsorbed in the small intestine
Megaloblastic anemia : occurs after 2 3 mo on a
folate- free diet.
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 .. Etiology

Acquired and congenital disorders of folate

metabolism :
Megaloblastic anemia : congenital dihydrofolate
reductase deficiency
Drugs induced abnormalities in folate metabolism :
Methotrexate
Pyrimethamine
Trimethoprim
Therapy : folinic acid is benefial

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 .. Folic acid
deficiency
CLINICAL MANIFESTATIONS

Megaloblastic anemia : the peak incidence at 4- 7 mo

of age.
Anemia, irritability, fail to gain weight adequately,
chronic diarrhea.
Hemorrhages from thrombocytopenia
Accompany : kwashiorkor, marasmus, or sprue.

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 .. Folic acid
deficiency

LABORATORIUM FINDINGS
Anemia is macrocytic (MCV > 100 fl)
Reticulocyte count :
Neutopenia & thrombocytopenia
Neutrophils : large & hypersegmented nuclei
Serum folic acid : < 3 ng/ml (N 5 20 ng/ml)
Levels of iron & vit. B12 : N or
LDH serum :
Bone marrow : hypercellular

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 .. Folic acid
deficiency
TREATMENT

Diagnosis of folate deficiency is established :

Folic acid can be orally or parenterally
Dose : 0.5 1 mg/day
Specific diagnosis is in doubt :
Smaller dose : 0.1 mg/day for a week diagnostic test
Transfusion : severe anemia or child is very ill.
Folic acid therapy (0.5 1 mg.day) : should be
continued for 3 4 weeks untills hematologic
response (+).
Maintenace therapy with multivitamin (containing
0.2 folate) is adequate.
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 VITAMIN B12 DEFICIENCY
ANEMIA
VITAMIN B12 :
Derived from cobalamin in food ( mainly animal sources)
secondary to production by microorganism.
Obtained primarily from :
Animal proteins (ie, red meat, poultry, fish, eggs, and dairy)
Plants and vegetables lack the vitamin unless they have been
contaminated by soil microorganisms

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Absorption of vit. B12
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 .. Vit. B12
deficiency

ETIOLOGY
Inadequate dietary intake of vitamin
Extreme dietary restriction (strict vegetarians or
vegan)
In children : breast-fed infants whose mothers are
vegans or pernicious anemia
Lack of IF (intrinsic factor) secretion by the stomach
Congenital pernicious anemia
Juvenile pernicious anemia
Gastric surgey
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 .. Etiology
Impaired intestinal absorption of IF cobalamin
Inflammatory diseases( regional enteritis or NEC)
Imerslund-Grasbeck Syndromes)
Absence of vitamin B12 transport protein
CLINICAL MANIFESTATIONS
Weakness, fatigue, failure to thrive, or irritability
Pallor, glossitis, vomiting, diarrhea, & icterus
Neurologic symptoms : parasthesias, sensory deficits,
hypotonia, seizures, developmental delay, &
neuropsychiatris changes.

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 .. Vit. B12 deficiency

LABORATORIUM FINDINGS
Macrocytic anemia (MCV > 100 fl)
RBCs : prominent macroovalocytosis
Neutrophil : large & hypersegmented
Neutropenia, thrombocytopenia, simulating apalstic
anemia or leukemia
Serum Vit. B12 levels : < 100 pg/ml
Serum iron & folic acid : Normal / elevated
Seru LDH :
Serum bilirubin levels : moderate elevations (2-3 mg/dl)
Methylmalonic acid in the urine : >>> (N 0 3.5
mg/24hrs)

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 .. Vit.B12 deficiency

TREATMENT
Prevention: total gastrectomy,ileal resection
prophylactic vit.B12 should be prescribe
Parenteral administration of vit. B12 (1mg)
reticulocytes begin increase on 3 4 days
The physiologic requirment for vit. B12 : 1 5 g/day
If evidence of neurologic involvement (+) : dose
1 mg/day (IM) for at least 2 weeks
Maintenance therapy : 100 g /sc monthly

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