Approach to a child

with anemia

Presented: Dr Shalom R2
Moderator: Dr Tadele
(Pediatrician, Hematologist/oncologist)
 Introduction
• Anemia is defined as a reduction of the
hemoglobin concentration or red blood cell
volume below the range of values occurring in
healthy persons.
• The threshold for defining anemia is a HCT or
HGB at or below the 2 standard deviation for
age, race, and sex.
 Normal values for hematocrit and
hemoglobin during the first year of life
 Prevalence
• Globally, WHO estimates 42% of less than 5
year old children have anemia.

• In Africa, 59.3% of under 5 were anemic

• In Ethiopia, WHO 2019 data shows a

prevalence of 52% anemia in children 6
months to 5 years of age.
Physiologic adjustments to anemia include
• Augmented oxygen extraction
• Increased cardiac output
• shunting of blood flow toward vital organs and
tissues
• concentration of 2,3-diphosphoglycerate
increases within the RBC
• Higher erythropoietin levels
“shift to the right” of the oxygen
dissociation curve
Difference between fetal and adult Hgb

• Fetal Hb binds to oxygen with high affinity

than adult Hgb to facilitate oxygen transfer
from the mother to fetus in utero
• It unloads oxygen to tissue readily
• Resists denaturation in acidic or alkali
environment
• Highest HCT occur at birth and reach nadir at
8 to 10 weeks
 Classification of anemia
1. Anemia may be morphologically categorized
on the basis of red cell size and microscopic
appearance.
• It can be classified as microcytic, normocytic,
or macrocytic
2. On the basis of underlying physiology
categorized
Decreased production
Increased destruction: secondary to
hemolysis, sequestration, or bleeding

• The peripheral blood reticulocyte percentage

or absolute number helps to distinguish
between the 2 physiologic categories.
 History
• The signs and symptoms of an anemia are a function of
its severity, its rapidity of onset, and the age of the
patient.
• Symptoms and signs appear when hemoglobin has
fallen below 7-8 g/dL,

• Rapidity of onset reflects the ability of the hemoglobin-

oxygen dissociation curve to compensate
 Long-standing anemia versus acute blood loss
 Age
 Neonate : blood loss, immune hemolytic disease,
congenital infection, twin-twin transfusion, and
congenital hemolytic anemia (hereditary
spherocytosis, G6DP), late hyporegnerative anemia
, pearson marrow pancrease syndrome

 6-9wks: physiologic anemia of infancy occur,

 3 to 6 weeks: anemia of prematurity
 3-6months: hemoglobinopathies
 6 months - 2 years nutritional aneamia
 Diamond blackfan syndrome: 2 to 6 months
 Transient erythroblastopenia of childhood: 3
month to 3 years
 Iron deficiency anaemia at 9 to 24 months
 Fanconi’s anaemia :4 to 6 years of age.
• AGE
Sex:
 X-linked: G6PD deficiency and X-linked sideroblastic
anemia
 Post-menarchial girls: Excessive menstrual bleeding

Race: hemoglobinopathies and enzymopathies

 Hemoglobin S and C: black and Hispanic populations
 Thalassemia syndromes : Mediterranean and
Southeast Asian descent;
 G6PD deficiency : Sephardic Jews, Filipinos, Greeks,
Sardinians, Kurds, and black population
Symptoms
 Infants: lethargy, tachycardia, pallor, irritability and poor oral
intake in infants
 Hemolysis − Changes in urine color, scleral icterus, or jaundice
 Bleeding symptoms − gastrointestinal tract-changes in stool
color, blood in stools, and history of bowel symptoms, epistaxis,
 menstrual history- duration and amount of bleeding
 Gastrointestinal: worm infestations, bleeding, family history of
IBD, intestinal polyps, small bowel resections,
 GU: reddish discoloration of urine, decrease urine
 Skin: rash, petechiae, purpura, ecchymosis, joint swelling
 CNS: Irritability, lethargy, Pica
Diet
 Assessing iron, folate and B12 content.
 Type of diet, type of formula, and age of infant
at the time of discontinuation of formula or
breast milk
 Amount
 exclusively fed goat's milk can develop anemia
due to folate deficiency
Milk source Iron Folate

Breast milk

Cow milk

Goat milk
Family history:
  Family members with jaundice, gallstones, or
splenomegaly should be identified.
 family members have undergone cholecystectomy or
splenectomy
Developmental history :
 Iron deficiency, vitamin B12/ folate deficiency, and
Fanconi anemia
Travel: Endemic infection (malaria, hepatitis, tuberculosis)
Medication  Current and past medications (herbal
supplements), oxidant drugs that can cause hemolysis esp
in G6PD deficiency
Environmental toxin exposure: lead exposure and
nitrates in well water.
Past medical history
 Previous CBC should be reviewed, and if prior
anemic episodes characterized by duration,
etiology, therapy, and resolution)
 Underlying medical condition: renal disease,
RVI, tuberculosis,
Physical examination
 Focus should be directed to examination of
the skin, eyes, mouth, face, chest, hands, and
abdomen
 Pallor is assessed by examining sites where
capillary beds are visible
 Sensitivity of clinical assessment of pallor
approximately 50 to 60 %
• General Appearance: Acute or chronically sick
looking, malnutrtion, stunting
• Vital signs: hypotension, tachycardia, tachypnea,
fever
• HEENT: Pale conjunctiva, angular chelitis, icterus,
malar prominence,
• LN: Lymphadenopathy
• Respiratory:
• CVS: bounding pulse, wide pulse pressure,
tachycardia, hypotension, flow murmur
• Abdomen: hepatosplenomegally,
• GUS: Renal malformation
• MSS: Spooning of nail beds, triphalngeal
thumb, short stature,
• Integumentary: pallor, petechiae, echymosis,
• CNS: mental retardation,
Investigations
• CBC
• RBC indices
• Blood smear
• Reticulocyte count
• Iron study
• Bone marrow
aspiration and biopsy
• Stool exam • Renal function test
• Blood film • Liver function test
• LDH • Autoimmnue marker:
• Bilirubin ANA
• Coombs test • Osmotic fragility test
• Haptoglobin level • Electrophorsis
• Serum vit B12/ folate • Chromosome analysis
study
A. Hematocrit is the fractional volume of a
whole blood sample occupied by RBCs,
expressed as a percentage.
B. Hemoglobin a measure of the concentration
of the RBC pigment hemoglobin in whole blood,
expressed as grams per 100 mL (dL) of whole
blood
• At higher altitudes: predictable increases in
Hgb levels of 1 g/dL for each 3 %-4% decrease
in arterial oxygen saturation
C. Reticulocyte count
Reticulocytes are young red blood cells
containing residual ribosomal RNA
 Normal value: 1 % with a range of 0.6%-2%.
• The count needs to be corrected for both
changes in RBC count and the effect of
erythropoietin on reticulocyte release from
the marrow
 Reticulocyte count correction
1st correction
Absolute reticulocyte count = % of reticulocytes x
RBC count
 The ARC is an indication of bone marrow
erythropoietic activity and is used to classify the
bone marrow response to anemia
 Anemia with a high ARC reflects an increased
erythropoietic response to hemolysis or blood loss.
 Anemia with a low or normal ARC reflects a
reduced marrow response to the anemia
2nd correction
• Marrow reticulocytes are shifted out of the
marrow and into circulation at an earlier stage
with increasingly severe anemia.
• This process has the effect of lengthening the
maturation time of reticulocytes in circulation.
Reticulocyte index=
 Reticulocyte count x observed HCT * 1
normal HCT µ
μ is maturation factor of 1–3 related to the
severity of the anemia .
 Example
• A 11 month old infant presented with
yellowish discoloration of the eyes. Was
having preceding cough and fever.
D. Mean cell volume
• MCV : mean value of the volume of individual
RBCs in the blood sample
MCV= HCT% *10
RBC
• 70 +age in years: estimate lower level of MCV
• less sensitive to the presence of small
populations of microcytes or macrocytes.
• Misleading- RBC agglutination, distortions in cell
shape, very high numbers of white blood cells,
and sudden osmotic swelling in hyperglycemia
and hypernatremia
E. Mean cell hemoglobin
• MCH: amount of hemoglobin in each
individual red blood cell
MCH=HGB*10
RBC
• Patients with iron deficiency or thalassemia
who are unable to synthesize normal amounts
of hemoglobin show significant reductions in
the MCH.
G. Mean Corpuscular Hemoglobin
Concentration(MCHC):measurement of the
relative concentration of intracellular
hemoglobin
MCHC=HGB *100%
HCT
• principal value of the MCHC is to detect
patients with hereditary spherocytosis
• LOW: IDA
• HIGH: Spheocytosis
F. Red cell distribution width
RDW-CV RDW-SD
 ratio of the width of  direct measurement of
the red blood cell the red blood cell
distribution curve at 1 distribution
SD divided by the MCV • width taken at the 20%
• normal RDW-CV = 13 ± frequency level
1% • more sensitive to the
• MCV will influence the appearance of minor
result. populations
Mentzer index is defined as Mean Corpuscular
Volume per Red Cell Count (MCV/RBC Count),
value < 13 states hemoglobin defect,
value >13 suggests iron deficiency.
Peripheral morphology
o RBC size – A normal RBC should have the same
diameter as the nucleus of a small lymphocyte
o Central pallor – The normal mature RBC is a
biconcave disc ly one-third the diameter of the
cell
o spherocytosis and reticulocytes do not display central
pallor, because they are not biconcave discs.
o Fragmented cells presence of small numbers of
fragmented cells, indicating a microangiopathic
process
o Sickle cells: sickle cell disease
o Stomatocytes: hereditary or acquired
stomatocytosis
o Pencil poikilocytes: iron deficiency anemia or
thalassemia
o Target cells: hemoglobinopathies, including
thalassemia, liver disease, and post-splenectomy
o Bite cells and Heinz bodies: hemolytic anemia
due to oxidant sensitivity, such as G6PD
deficiency.
o Red blood cell agglutination: cold agglutinin
hemolytic anemia
o Howell-Jolly bodies: absence or hypofunction
of the spleen.
o Basophilic stippling: classically seen in lead
poisoning, thalassemia, sickle cell anemia, and
sideroblastic anemia.
o Hypersegmented neutrophils suggest vitamin
B12 or folate deficiency.
o Blast cells : leukemia or lymphoma.
IDA
Megaloblast
Spherocytes
Target cells
Sickle cell anemia
Howell-Jolly bodies
 Iron study
• Serum iron level is a measure of the
amount of iron bound to transferrin.
• Normal value of 50-150 µg/dL and below 50
µg/dL the erythroid marrow cannot increase
production above basal levels
Total iron-binding capacity is a measure of the amount
of iron that can be bound by transferrin.
• Normal TIBC is 300-360 µg/dL.
• TIBC changes independently of the serum iron in situations of
iron deficiency.
• The TIBC is used to calculate percent saturation of transferrin
% saturation= Serum Iron
TIBC

Normal :20% - 50%

IDA <10%
 Serum ferritin is used to evaluate body iron
stores.
• A normal 50-150 µg/L, reflects iron stores of
600-1,000 mg.
• 10-15 µg/L indicate store exhaustion and iron
deficiency
 Serum transferrin receptor level- reflect the
level of expression of receptors on erythroid
precursor cells’ surface and the absolute
number of erythroid precursors.
• serum TfR increases with both iron deficiency
and erythroid precursor proliferation.
• It can be useful in the differential diagnosis
of absolute iron deficiency versus the anemia
of chronic disease
Laboratory findings in the differential diagnosis of iron deficiency
anemia
Lab Iron deficiency Alpha/beta Anemia of chronic disease
anemia thalassemia

Hemoglobin Decreased Decreased Decreased

MCV Decreased Decreased Normal-decreased

Red cell distribution Increased Normal Normal-increased

width
Erythrocyte Increased Normal Increased
protoporphyrin
Total iron-binding Increased Normal Decreased
capacity
Transferrin Decreased Normal Decreased
saturation
Serum ferritin Decreased normal Increased
Transferrin receptor Increased Normal Increased
Hypo-proliferative anemia panel
Cytometric assay of CDS9/CDSS
levels : :paroxysmal nocturnal hemoglobinuria
Chromosomal analysis: leukemias
Marrow aspirate/biopsy special stains
 Trichrome stain (myelofibrosis)
 Silver stain for reticulin (myelofibrosis)
 Peroxidase, esterase, and PAS stains :acute
leukemia
Maturation disorders
Serum vitamin B 12 level
Serum/red blood cell folate level
Urine/serum methylmalonic acid level (B12 and folate
deficiency)
Hemoglobin electrophoresis : thalassemia
Hemoglobin A2 level: Beta-thalassemia
Hemoglobin F level-Beta thalassemia
Red blood cell protoporphyrin level (iron deficiency-lead
poisoning)
Hemolytic anemia panel
Hemoglobin electrophoresis : hemoglobinopathies
Coombs test :autoimmune hemolytic anemia
Cold agglutinin titer: autoimmune hemolytic anemia
Haptoglobin level : hemolysis
Serum/urine hemosiderin : intravascular hemolysis
Osmotic fragility : hereditary spherocytosis
G6PD screen
 Reference
• Clinical hematology 5th edition
• Uptodate 2018
• Nelson 21st edition
• Post graduate hematology 5th edition