APPROACH TO PALE CHILD

Anemia is defined as a hemoglobin

concentration or red blood cell (RBC) mass
less than the 5th percentile for age.


MECHANISM / PHYSIOLOGIC
CLASSIFICATION
Reduced red cell
production
Nutritional : Folic acid,
B12, Ferum, Ascorbic
acid
Mechanical :
Malignancy
Dyserythropoiesis
Blood loss (acute and
chronic)
Blood destruction
Hemoglobinopathies
Structural : Sickle
Synthetic : Thalassemia
RBC enzyme defects :G6PD
Membrane defects :
Hereditary spherocytosis
Immune mechanism : auto or
allo
Infectious agents
Chemical : Heavy metal,
oxidant
Physical trauma : thermal
injury, microangiopathy
MORPHOLOGIC CLASSIFICATION
Microcytic Normocytic Macrocytic
Low retic High retic
Iron deficiency Bone marrow
infiltration
Acute blood loss Folic acid
deficiency
Thalassaemia trait Transient erthro
blastopenia in
childhood
Hemolysis
Extrinsic
-Antibody mediated
- Fragmentation : DIC, HUS,
prosthetic heart valve
Intrinsic
- Membrane disorders:
Spherocytosis
-Enzyme deficiencies: G6PD
- Hemoglobin disorder: Sickle cell
Vitamin B12
deficiency
Chronic disease Chronic disease Hypothyroidism
Sideroblastic
anemia
Aplastic anemia Liver disease
Lead poisoning
IRON DEFICIENCY
Causes:
Inadequate intake
Malabsorption (Worm
infestation)
Chronic blood loss
Increase demand
(Prematurity, Growth)
Clinical features
Pica
Tired easily
Feed more slowly (infants)
Investigation :
Low MCH, MCV
Low serum ferritin

Management
Dietary advice
Supplement with oral
iron
failure to respond
Non compliance
Inadequate iron dosage
Investigate other causes
- Malabsorption ( Coeliac
disease)
- Chronic blood loss (Meckels
diverticulum)


HEMOLYTIC ANEMIA
Definition: Reduced red
cell lifespan
Due to increased red
cell destruction

Circulation liver /
(intravascular) spleen
(extravascular)
# Anemia when bone marrow is no
longer able to compensate for
the premature destruction of red
cells.

Increased red cell
breakdown causes:

Reticuloendothelial hyperplasia
(hepatomegaly and
splenomegaly)
anemia
Elevated
unconjugated
bilirubin
Excess urinary
urobilinogen
Diagnostic clues :
Raised reticulocyte count
Abnormal appearance of
red cells on blood film
Positive direct
antiglobulin test (only if
an immune cause)
Increased erythropoiesis
in bone marrow.
Intrinsic abnormalities of
red blood cell:
(a) Red cell membrane
disorders (hereditary
spherocytosis)
(b) Red cell enzyme
disorders (glucose 6
phosphate
dehydrogenase
deficiency)
(c) Haemoglobinopathies
(Beta thalassaemia,
sickle cell disease)
MCV
RBC
Mentzer index
-<13 suggests
thalassemia
>13 suggests
Iron deficiency
HEREDITARY SPHEROCYTOSIS
Autosomal dominant inheritance
25% : new mutations
Inherited, intrinsic and membrane
defect
RBCs- spheroidal , less deformable
and vulnerable to splenic
destruction

Clinical features
- Asymptomatic
- Jaundice - intermittent
- Anemia
- Mild to moderate splenomegaly
- Aplastic crisis (associated with
parvovirus B19 infection)
- Gallstones (due to increased
bilirubin excretion)

Diagnosis
- Reticulocytosis, Elevated
MCHC
- Blood film
- Osmotic fragility increased,
dye binding test
- Normal direct antibody test

Management
- Folic acid 1mg day
- Splenectomy (if poor growth /
troublesome symptoms or
anemia)
- Cholecystectomy
(symptomatic gallstones)


G6PD DEFICIENCY
Rate limiting enzyme in the
pentose phosphate pathway
Preventing oxidative damage
to red cells - Susceptible to
oxidant induced hemolysis
X linked (predominantly
affects male)
Clinical features:
- Neonatal jaundice
- Acute hemolysis precipitated
by infections, drugs, fava
beans, naphthalene
- Intravascular hemolysis
associated with fever, malasie,
dark urine
Diagnosis : measure G6PD
activity
Management: educate
parents on list of drugs,
chemical and food to avoid.
HAEMOGLOBINOPATHIES
SICKLE CELL DISEASE
- HbS inherited
- HbS forms as a result of a
point mutation in codon
of -globin gene (change
in glutamine to valine)
- Forms:
(a) Sickle cell anemia
(b) SC disease
(c) Sickle -Thalassaemia

Pathogenesis
- In HbSS, the Hb molecule
becomes deformed
(insoluble) in the
deoxygenated state

Sickle cell disease: Clinical features
Anemia
Infection
Painful crises
Splenomegaly
Long term problems
- Short stature and delayed
puberty
- Adenotonsillar hypertrophy
- Cardiac enlargement /
Heart failure
- Renal dysfunction
- Pigment gallstones



Sickle cell disease: Treatment
Treatment is directed toward prevention of
complication and optimization of health
Immunized with conjugate pneumococcal
vaccine penicillin prophylaxis 125 mg twice
daily (2 months), increase to 250 mg twice a
day at 3 years until 5 years old
Folate supplementation
-Thalassaemia major
is an autosomal recessive
inheritance of mutations in
each of two -globin genes
Clinical features:
- Severe anaemia and
jaundice from 3-6 months
of age
- Failure to thrive / growth
failure
- Extramedullary
haemopoiesis causes bone
marrow expansion >
classical facies with
maxillary overgrowth, skull
bossing
Management:
- regular maintenance
blood transfusion and
iron chelation therapy
(transfusion dependent
thalassaemia

APPROACH
symptoms
Irritability
Pica
Jaundice
SOB
Palpitations
examinations
Jaundice
Tachypnea
Tachycardia
Heart failure
(severe or acute)
Chronic anemia
(glossitis, flow
murmur, growth
delay).
Transfusion target
- Pre transfusion Hb: 9-10
g/dL
- Post transfusion Hb: 13.5-
15.5 g/dL
- Mean Hb 12-12.5g/dL
Transfusion interval 4
monthly ( Hb decline 1
g/dL/week)
Volume: 15-20 ml/kg
Packed red cells
Iron chelation therapy
- Desferrioxamine (DFO)-
desferal, Deferiprone
(DFP), Deferasirox (DFX) -
Exjade

AUTOIMMUNE HEMOLYTIC DISEASE
(AIHA)
Characterised by the
production of antibodies
directed against RBC.
Follows viral infection or
vaccination more often in
children
Secondary causes:
Immunodeficiency,
malignancy, SLE, and other
types of collagen vascular
diseases.
Acute self limited illness
Good response to short term
steroid therapy in 80% of
patients.
Can be insidious with
tendency to become chronic.


Investigations
Reticulocytosis
Elevations in levels of lactate
dehydrogenase and aspartate
aminotransferase refl ect the
release of intraerythrocyte
enzymes
direct antiglobulin test
(Coombs test), which
identifies antibodies and
complement components on
the surface of circulating
erythrocytes.

Treatment depends on
severity
Optimal therapy depends on
the clinical picture, as well as
the form of AIHA.
If the autoantibodiesare cold
reactive, for example, the
patient should be kept warm
with avoidance of all cold
stimuli.
Therapy for acute warm-
reactive AIHA in children
should begin with close
observation, judicious use of
erythrocyte transfusions, and
administration of
corticosteroids.

Additional therapy
includes the
administration of
intravenous
immunoglobulin (IVIG),
plasma (exchange)
transfusion in selected
settings, and more
recently, targeted therapy
with rituximab.
PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
Ongoing intravascular
hemolysis with intermittent
episodes of dark urine
(hemoglobinuria)
common on awakening in
the morning
Intracorpuscular defect
because hemolysis result
from increased sensitivity of
patients erythrocytes to
physiologic complement
mediated lysis

LEUKAEMIA
Acute lymphoblastic
leukaemia (ALL) accounts for
80% of leukaemia in children.
Most of the remainder are
acute myeloid/acute non-
lymphocytic (AML/ANLL)
leukaemia.
Chronic myeloid leukaemia
and other myeloproliferative
disorders are rare.
Clinical symptoms and signs
result from infiltration of the
bone marrow or other organs
with leukaemic blast cells

In most children, leukaemia
presents insidiously over
several weeks
The blood count is abnormal,
with low haemoglobin and
thrombocytopenia and
evidence of circulating blast
cells.
Bone marrow examination is
essential to confirm the
diagnosis and to identify
immunological and
cytogenetic characteristics
which give useful prognostic
information.

VITAMIN B12 DEFICIENCY
Causes
Diet
Lack of intrinsic factor (IF) congenital
pernicious anemia : autosomal recessive
disorder due to an inability to secrete
gastric IF or secrete abnormal IF
Impaired vitamin B12 absorption
regional enteritis or neonatal necrotising
enterocolitis
Absence of vitamin B12 transport
protein
Clinical manifestation
Weakness, Fatigue, irritability
Failure to thrive
Pallor, glossitis
Vomiting, diarrhea
Neurologic : paresthesias, hypotonia,
developmental delay


Investigations
Serum vitamin B 12 less than 100
pg/mL
Serum LDH increased (ineffective
erythropoiesis)
Excretion of methylmalonic acid in
the urine (0-3.5 mg/24 hours)
Treatment
Physiologic requirement : 1-5 g /
day
If evidence of neurologic involvement
1 mg should be injected
intramuscularly daily for at least
2week.
Maintenance monthly IM
administration 1 mg
FOLIC ACID DEFICIENCY
Causes
Inadequate folate intake
Decreased folate absorption
Congenital or acquired
abnormalities in folate
metabolism
Clinical features
Anemia
Irritable
Fail to gain weight adequately
Chronic diarrhea
Hemorrhages from
thrombocytopenia in
advanced cases
Normal serum folic acid 5-20
ng/mL
LDH increased
Treatment:
- Folic acid 0.5-1 mg
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REFERENCES
Evaluation of anemia by Jennifer et al, American Family
Physician, June 15 2010 Volume 81,Number 12.
Paediatric protocol third edition
Nathan and Oskis hematology of infancy and
childhood 7
th
edition
Autoimmune hemolytic anemia in children and
adolescents by Sarper et al, Turk J Hematol
2011;28:198-205.
Illustrated textbook of Paediatrics, third edition
Nelson textbook of paediatrics, 19
th
edition