Anaemia in children: content

• Definition and normal values

• Classification and aetiological approach:
- History and Physical
- Investigation
• Treatment
 Definition of Anaemia
• From Greek anaimia,
(an- ‘without’ + haima‘blood’)

• Hb and/or hct < 2 SD of mean for reference

population (race)

• It depends on:
- age
- gender (after puberty)
- altitude of domicile
 Definition
WHO cut off point for anaemia (1996):
6mo – 5 yrs: <11 g/dl
5-11 yrs: <11.5 g/dl
12-13 yrs: <12 g/dl
Adult men: <13 g/dl
woman: <12 g/dl
pregnant: <11 g/dl
 Classification according to severity

Anaemia severity and Hb level

• Mild: 10-11 g/dL
• Moderate: 8-10 g/dL
• Severe: <8 g/dL

Results in inadequate RBC to carry O2 to tissues

Checking for anaemia (pallor)

Conjunctival pallor.
The presence of scleral jaundice
may suggest haemolytic anaemia
 Why Hb levels differ with age
• No satisfactory answer
• Children RBC have more
- inorganic phosphate (50% more)
- ATP and 2,3 DPG (how children rbc could have
more 2,3 dpg when fetal hemoglobin has no beta
chain, also doesn’t anemia causes raise in 2,3 DPG
instead of vice versa)
• Hence decreased oxygen affinity, thus requiring
less Hb (but anemia also causes rise in 2,3 DPG)
Function of 2,3 DPG
• Binds to beta-chain of one tetramer of
deoxyhaemoglobin, causes conformational
change that reduces O2 affinity (displacing
dissociation curve to the right).
• => Increased levels of 2,3 DPG
• => reduced the affinity of haemoglobin
• => Right shift of ODC
•
 Physiological anaemia of infancy
• Hb declines by 8-12 wks of life to 9-11 gm/dL
• Hypoxia stimulates erythropoietin production
• In preterm, Hb decline more severe and rapid –
Hb drops to 7-9 gm/dl by 3-6 wks old.
immature erythropoietin response
• Transition from HbF to HbA
- first 34-36 weeks, 85-90 % of Hb is HbF
- after 36 weeks, HbF constitutes 50-65%
- at 3 months after birth, HbF ~ 5%
• After birth, RBC mass normally declines in
response to an increase in the availability of
oxygen and downregulation of erythropoietin.
RBC count decreases until oxygen delivery is
inadequate for metabolic demand and
erythropoietin production is stimulated again.
In healthy term infants, the RBC nadir, a
physiologic response to postnatal life and not
a hematologic disorder, typically occurs at 8
to 12 weeks of life and at a hemoglobin level
of 9 to 11 g/dL.
 Content
• Definition and normal values
• Classification and diagnostic approach:
- History and Physical
- Investigation
• Treatment
 Aetiology of anaemia by pathophysiology

• Inadequate production:
- nutritional deficiency (e.g. iron, folate, B12),
- ineffective erythropoiesis/ dyshaemopoiesis
• Marrow failure
- aplastic anaemia
- marrow infiltration (e.g. leukaemia)
• Rapid RBC destruction/ haemolysis
- immune causes
- nonimmune causes
• Blood loss
 Aetiology by erythropoietic (reticulocyte)
response
• Elevated reticulocyte (reticulocyte production index >2%)
- chronic blood loss or
- haemolysis
( PS: retic response occurs only a few days/ a wk after event)

• Decreased or normal reticulocyte (reticulocyte production index <2%)

Indicates hypoproliferative anaemia:
- vitamin or mineral deficiency (e.g. iron, B12, folate deficiencies)
- bone marrow depression/destruction/replacement
(e.g. malignancy, chronic infection/inflammation, drugs, aplastic
anaemia, parvovirus infection)
- defective RBC production e.g. pure red cell aplasia, renal failure, lead
poisoning
 Aetiology by RBC morphology (size):
• Microcytic (75fl) (< 6 micrometer)
• Normocytic (76-99fl) (6-9 micrometer)
• Macrocytic (100fl) (>9 micrometer)

* MCV errors can occur due to delayed analysis

time and in reticulocytosis
* MCV at birth range 95 to 120 fl; microcytosis is
defined as MCV <95fl in neonates
 Content
• Definition and normal values
• Classification and diagnostic approach:
-History and Physical
-Investigation
• Treatment
 Focused history
• Symptoms related to anaemia
• Onset:
Acute or chronic
• Jaundice and red/dark urine
• Systemic illness
• Dietary history, PICA
• Medications/toxins exposure
• Psycho/neurological changes – B12 or folate def,
• Birth and neonatal history: jaundice, screening
• Family history: Anaemia
• Surgery e.g. Splenectomy, Gall bladder surgery
• Social history
 Signs and symptoms
• May be asymptomatic apart from pallor .
• Symptoms depends on onset
• General signs and symptoms of severe anaemia
are due to
-Tissue hypoxia e.g. fatigue, weakness, headache,
tinnitus, light headedness, dizziness, irritability,
tinnitus, sleep disturbance
-Cardiovascular effect e.g. tachycardia,
palpitation, exertional dyspnoea i.e. cardiac
failure
 Physical findings
• Associated lymphadenopathy may
suggest that a suggest anaemia due to leukemia

Hepatosplenomegaly may suggest

anaemia due to chronic haemolysis or
infiltrative disease (e.g. leukemia)
 Content
• Definition and normal values
• Classification and diagnostic approach:
- History and Physical
- Investigations
• Treatment
 Useful initial investigations
• FBC – anaemia, pancytopenia?
• Reticulocyte (supravital stain) ->
• MCV – microcytic, macrocytic,
normocytic
• RDW
• PBF – any abnormalities?
 MCV: Macrocytic anaemia
• B12 def: pernicious anaemia, ileal resection,
abnormal intestinal transport
• Folate def: malnutrition, malabsorption, drugs,
chronic haemolysis
• Hypothyroidism
• Chronic liver failure
• Marrow failure: Fanconi anaemia, Aplastic
anaemia
• Myelodysplasia, Down syndrome
• Reticulocytosis
 MCV: Microcytic anaemia
Usually associated with hypochromasia
• Fe deficiency
• Thalassaemia
• Sickle cell anaemia
• Sideroblastic anaemia
• Chronic infection
• Lead poisoning
• Copper deficiency
• IE of Iron metabolism
• Severe malnutrition
 MCV: Normocytic anaemia
(with decreased or normal retics)
• Physiological anaemia
• Pure red cell aplasia
• Marrow infiltration
• Marrow failure; aplastic anaemia
• Dyserythropoietic anaemia
• Infection
• Renal failure, liver failure
• Connective tissue disease
• Early iron deficiency
 MCV: Normocytic anaemia
(with increased retics)
• Blood loss

• Haemolysis:
- Inherited:
RBC membrane: spherocytosis, ovalocytosis
haemoglobin: thalassaemia (alpha and beta)
enzyme/metabolic: Glucose 6 Phosphate Dehydrogenase deficiency
Pyruvate Kinase deficiencies
- Acquired:
immune: Autoimmune Haemolytic Anaemia (warm & cold antibody)
Iso immune (Rh, ABO incompatibility)
non immune: microangiopathy (HUS), infection, drugs
 Useful initial investigations
• FBC – anaemia, pancytopenia?
• Reticulocyte (supravital stain) ->
• MCV – microcytic, macrocytic,
normocytic
• RDW
• PBF – any abnormalities?
 Useful initial investigations
• FBC – anaemia, pancytopenia?
• Reticulocyte (supravital stain) ->
• MCV – microcytic, macrocytic,
normocytic
• RDW
• PBF – any abnormalities?
 PBF (RBC morphology)
• Leucoerythroblastic smear
• Anisocytosis – RBC of abnormal sizes
• Poikilocytosis – abnormal shapes: elliptocyte,
spherocytes, dacrocyte, bite cell, sickle cell
• Spiculated/crenated/burr cell, schistocytes
• Target cell
• Heinz body
• Howell-Jolly bodies
• Cabot ring
• Basophilic stippling
 Abnormal RBC morphology:
leucoerythroblastic smear

• Teardrop cells, nucleated red cells, and

immature white cells
• Not normally found in PBF.
• Appear in hypoxemia, severe haemolysis
myelofibrosis or other myelophthisis
 Abnormal RBC morphology:
polychromasia
Polychromatophilia (blue hue of cytoplasm) due
to presence of RNA and ribosomes in reticulocytes.
 Abnormal RBC morphology
Teardrop cell/dacryocyte
• Found in myelofibrosis and other
myelophthisic (displacement) states of bone
marrow
 Abnormal RBC morphology
Bite cell
• Cells with a smooth semicircle extracted due to
spleen phagocytes that have removed Heinz
bodies consisting of denatured Hb.
• Found in hemolysis due to G6PD def.
 Abnormal RBC morphology
Sickle cell
• Due to to polymerization of Hb S.
• Occurs from substitution of a valine for glu as
6th AA of beta chain, resulting in abnormal Hb
tetramer alpha2/beta S2
• Poorly soluble when
deoxygenated.
• Found in SCD but not
in sickle cell trait.
 Abnormal RBC morphology:
Burr/crenated cells
• Cells with short, evenly spaced cytoplasmic
projections
• May be an artifact
of slide preparation
or in renal failure.
 Abnormal RBC morphology:
Acanthocyte
• Speculated cells with irregular projections of
varying length
• Often seen in
liver disease.
 Abnormal RBC morphology:
Schistocytes
• Fragmented cells
• Caused by mechanical disruption of cells in the
microvasculature
by fibrin strands
or by mechanical
prosthetic heart
valves.
HUS, DIC,
 Abnormal RBC morphology
Target cells
• Cells with extra Hb in center surrounded by rim
of pallor from redundancy in cell membrane;
“bull’s eye appearance”
• Found in liver disease,
post splenectomy, and
in hemoglobinopathies.
 Abnormal RBC morphology
Heinz bodies
• Inclusions seen on staining with violet crystal
• Represent denatured Hb
• Found in G6PD
after oxidative stress
 Abnormal RBC morphology:
Howell Jolly body
• Small, single, spherical blue-black cytoplasmic inclusions of
RBC seen on Wright-stained smears.
• Nuclear fragments of condensed DNA, 1 to 2 µm in diameter,
normally removed by the spleen.
• Seen in severe hemolytic
anemias, in patients with
dysfunctional spleens
or after splenectomy.
l
 Abnormal RBC morphology:
Cabot rings
• Thin, red-violet threadlike strands in the shape of a loop or
figure-8 that are found rarely in RBC
• Believed to be microtubules that are remnants of mitotic
spindle.
• Seen occasionally
megaloblastic anemia,
Pb poisoning and
other disorders of
erythropoiesis.
•
 Abnormal RBC morphology:
Basophilic stippling
• Dark-purple inclusions, usually multiple
• Arises from precipitated RNA found in lead
poisoning and
thalassemia.
 Abnormal RBC morphology:
Spherocytes
• Round, dense cells with an absent central pallor
• Seen in immune
hemolytic anemia
and hereditary
spherocytosis.
 Abnormal RBC morphology:
Ovalocyte/elliptocyte
• Due to abnormal membrane cytoskeleton
• Found in
ovalocytosis
 Normal RBC morphology
• Chronic inflammatory disease:
- infection, HIV
- chronic vascular disease
- inflammatory bowel disease
• Recent blood loss
• Malignancy
• Bone Marrow infiltration, aplasia/hypoplasia
• Haemophagocytic syndrome
• Chronic renal failure
• Transient erythroblastopenia of childhood
 Additional investigations
• Iron studies
• Haemoglobin analysis
• In normocytic RBC index :
Total and unconjugated bilirubin
Direct anti-globulin test
Urine: inspection, urine Hb, urobilinogen, heamosiderin
Serum haptoglobin
• In macrocytic RBC index:
Vitamin B12 and serum folate
 Other specific investigations:

• Osmotic fragility test (Hereditary spherocytosis)

• RBC enzyme studies (e.g. G6PD)
• Bone marrow examination
• Hb analysis
• Alpha-globin chain analysis
• Tagged red cell survival
 Timing of investigations
The following tests if need to be performed, must be
done prior to RBC transfusion:
• All diagnostic studies
• Extended RBC grouping, especially chronic RBC transfusion
is anticipated
• Hepatitis B, Hepatitis C and HIV serostatus

Lapse of 3 months after transfusion is necessary for the

following tests:
• G6PD enzyme activity
• Hb analysis (may be difficult to interpret in infants < 6
months)
 Content
• Definition and normal values
• Classification and diagnostic approach:
- History and Physical
- Investigation
• Treatment
 Anaemia: treatment
• Safe and appropriate transfusion
• Other supportive treatment
• Genetic counselling
• Specific treatment :
- Treatment of underlying cause
- Immunosuppressive therapy
- Haemotopoietic stem cell transplantation
- Erythropoietin