Haematology (anaemia)

Question 1

What is anaemia defined as in children?

Answer 1

o Neonate: Hb <14
o 1-12 months: Hb<10
o 1-12 years: Hb <11

Question 2

How does foetal and adult haemoglobin differ?

Answer 2

o Foetal Hb (HbF) is made of two alpha units and two gamma units- it has a higher affinity for oxygen than adult Hb
o Adult Hb (HbA) is made of two alpha unity and two beta units
o HbF is gradually replaced by HbA in the first year of life- by 1, the percentage of remaining HbF is very low
• At birth (term)- Hb is high (14-21.5g/dL) to compensate for the low O2 concentration in the foetus, Hb falls over the first few weeks, due to RBC production, and reaches 10g/dL at 2 months of age

Question 3

What are the causes of IDA?

Answer 3

o Inadequate intake
o Malabsorption
o Blood loss (rare)
additional iron is required for the increase in blood
volume accompanying growth and to build up the child’s iron stores
• Iron can come from breast milk (50% absorbed – by far the best source)- may come from a delay in weaning
• Iron is best absorbed with vitamin c and without tannin from tea (or red wine!)

Question 4

What are the clinical features of IDA?

Answer 4

not present until below 6-7 g/dl
Lethargy
Feed slowly
Pale- conjunctiva, tongue or palmar creases

Question 5

How is IDA diagnosed?

Answer 5

microcytic, hypochromic anaemia (low MCV & MCH) and low serum ferritin

Question 6

What are the dietary sources of iron?

Answer 6

o	Foods to avoid in excess in toddlers
Cow’s milk
Tea- tannin inhibits iron uptake
High fibre foods- phytates inhibits iron absorption
o	High in iron
Red meat
Liver/kidney
Oily fish
o	Average iron
Pulses, beans & peas
Fortified breakfast cereals with added vitamin C
Wholemeal products
Dark green vegetables-
broccoli, spinach
Dried fruit- raisins, sultanas
Nuts & seeds- cashews or peanut butter

Question 7

What are the main causes of haemolytic in children?

Answer 7

o	Red cell membrane disorders (e.g. hereditary spherocytosis)
o	Red cell enzyme disorders (e.g. glucose-6-phosphate dehydrogenase deficiency)
o	Haemoglobinopathies (abnormal haemoglobins, e.g. β-thalassaemia major, sickle cell disease).

Question 8

What does haemolysis from increased red cell breakdown lead to?

Answer 8

o Anaemia
o Hepatomegaly and splenomegaly
o Increased blood levels of unconjugated bilirubin
o Excess urinary urobilinogen.

Question 9

What are the diagnostic clues for haemolysis?

Answer 9

o Raised reticulocyte count on the blood film- ‘polychromasia’ as the reticulocytes have a characteristic lilac colour
o Unconjugated bilirubinaemia and increased urinary urobilinogen
o Abnormal appearance of the red cells on a blood film  e.g. spherocytes, sickle shaped or very hypochromic
o Positive direct antiglobulin test- only if an immune cause, as this test identifies antibody-coated RBCs.
o Increased RBC precursors in the bone marrow

Question 10

What is hereditary spherocytosis?

Answer 10

1 in 5000 in caucasians
AD inheritance (25% no family history)
Mutations in genes for proteins of the red cell membrane- mainly spectrin, ankyrin or band 3
Red cell loses part of membrane when passing through spleen- reduction in SA:V
Cells become spheroidal, making them less deformable than normal and leads to their destruction in the microvasculature of the spleen

Question 11

What are the clinical features of hereditary spherocytosis?

Answer 11

o Jaundice: usually develops during childhood, but may be intermittent, may cause severe haemolytic jaundice in the first few days of life
o Anaemia: presents in childhood with mild anaemia, but the Hb level may transiently fall during infections
o Mild to moderate splenomegaly: depends on the rate of haemolysis
o Aplastic crisis: uncommon, transient (2-4weeks), caused by parovirus B19 infection
o Gallstones: due to increased bilirubin excretion

Question 12

What are the investigations for hereditary spherocytosis?

Answer 12

Blood film
osmotic fragility or dye binding tests
direct antibody test in the absence of a family history of hereditary spherocytosis- rule out autoimmune haemolytic anaemia

Question 13

What is the management for hereditary spherocytosis?

Answer 13

oral folic acid, as they have a raised requirement secondary to their increased RBC production
Splenectomy- poor growth, symptoms of anaemia- usually deferred until >7 because of post-op sepsis risk
Vaccinations- Hib, meningitis C, S. pneumoniae
Life long daily oral penicillin prophylaxis
• Aplastic crisis from parovirus B19 infection usually requires one or two blood transfusions over 3-4 weeks-
when no RBC are produced

Question 14

What is glucose-6-phospahte dehydrogenase deficiency (G6PD)?

Answer 14

commonest red cell enzymopathy
X-linked
• G6PD is the rate-limiting enzyme in the pentose phosphate pathway, it is essential for preventing oxidative damage to red cells, therefore RBCs lacking G6PD are susceptible to oxidant-induced haemolysis

Question 15

What are the clinical features of G6PD deficiency?

Answer 15

o	Neonatal jaundice- onset is usually in the first 3 days of life
o	Acute haemolysis precipitated by:
	Infection- most common
	certain drugs
	fava beans- broad beans
	naphthalene in mothballs.
Fever, malaise, dark urine 
Hb falls rapidly- may drop below 5 g/dl over 24–48 h

Question 16

What occurs between episodes in G6PD deficiency?

Answer 16

almost all patients have a completely normal blood picture and no jaundice or anaemia
diagnosis is made by measuring G6PD activity in red blood cells
during a haemolytic crisis, G6PD levels may be misleadingly elevated due to the higher enzyme concentration in reticulocyte
a repeat assay is then required in the steady state to confirm the diagnosis

Question 17

What are haemoglobinopathies?

Answer 17

red blood cell disorders which cause haemolytic anaemia because of reduced or absent production of HbA (α- and β-thalassaemias) or because of the production of an abnormal Hb e.g. sickle cell disease
• α-Thalassaemias- caused by deletions (occasionally mutations) in the α-globin gene
• β-Thalassaemia and sickle cell disease are caused by mutations in the β-globin gene
• Clinical manifestations of the haemoglobinopathies affecting the β-chain are delayed until after 6 months of age when most of the HbF present at birth has been replaced by adult HbA