Haem: Paediatric haematology Pt.1

Question 1

Which feature of children predisposes them to nutrient deficiencies?

Answer 1

Rapid growth

Question 2

What are the main differences between the blood count of neonate and an adult?

Answer 2

• Higher WCC (neutrophils, lymphocytes)
• Higher Hb
• Higher MCV

Question 3

How are the enzyme levels in the red blood cells of neonates different to adults?

Answer 3

They have 50% of the concentration of G6PD of adults

Question 4

List some causes of polycythaemia in a foetus.

Answer 4

• Twin-to-twin transfusion syndrome (recepient twin)
• Intrauterine hypoxia
• Placental insufficiency

Question 5

List some causes of anaemia in a foetus.

Answer 5

• Twin-to-twin transfusion syndrome (donor twin)
• Foetal-to-maternal transfusion (foetomaternal haemorrhage)
• Parvovirus infection
• Bleeding from cord or placenta

Question 6

When does the first mutation that leads to childhood leukaemia often occur?

Answer 6

In utero

Question 7

What is transient abnormal myelopoiesis (TAM) and what congential condition is assoicated with?

Answer 7

• congenital leukaemia
• The presence of preleukaemic blasts in the bone marrow and blood of a neonate
• 20% of these children will develop myeloid leukaemia within 4 years
• Associated with Down’s syndrome

Question 8

What lineage is the myeloid leukaemia associated with TAM?

Answer 8

Megakaryocyte

Question 9

Define thalassaemia.

Answer 9

A group of conditions resulting from a reduced rate of synthesis of one or more globin chains as a result of a genetic defect.

Question 10

Define haemoglobinopathy.

Answer 10

Conditions characterised by synthesis of structurally abnormal haemoglobin.

NOTE: thalassemias are sometimes considered a form of haemoglobinopathy

Question 11

On which chromosomes are the different globin genes expressed?

Answer 11

Beta chain - chromosome 11

• Beta
• Delta
• Gamma
• Epsilon

Alpha chain - chromosome 16

• Alpha 1 and 2
• Zeta

Question 12

What is the globin chain composition of the following types of haemoglobin:

1. HbA
2. HbA2
3. HbF

Answer 12

1. HbA = 2 alpha, 2 beta
2. HbA2 = 2 alpha, 2 delta
3. HbF = 2 alpha, 2 gamma

Question 13

What is the normal HbA2 level in a healthy adult?

Answer 13

< 3.5%

Question 14

Which foetal haemoglobins are present in the first 16 weeks?

Answer 14

• Gower 1 (2 zeta, 2 epsilon)
• Gower 2 (2 alpha, 2 epsilon)
• Portland 1 (2 zeta, 2 gamma)

Question 15

Describe how the different haemoglobin levels in utero and in the first year of life change.

Answer 15

• Haemoglobin Gower 1 and 2 and Portland are present in the first 16 weeks
• HbF predominates throughout most of foetal life and is present until 9 months postpartum
• HbA slowly starts around 2 weeks. After 32 weeks, there is a rapid increase in production
• HbA2 starts being synthesised at 28 weeks

Question 16

What are the proportions of HbA and HbF at birth?

Answer 16

1/3 HbA
2/3 HbF

Question 17

What is the difference between sickle cell anaemia and sickle cell disease?

Answer 17

• Sickle cell anaemia - homozygosity for HbS gene
• Sickle cell disease - encompasses homozygous and heterozygous states associated with sickling (including HbSC and HbS/beta thalassemia)

Question 18

Outline the pathophysiology of sickle cell anaemia (specifically mechanims of sickling)

Answer 18

• Hypoxia induces HbS polymerisation and subsequent sickling of RBC
• RBCs become more adeherent to the endothelium and lead vessel occlusion
• This tends to occur in the post-capillary venule

Question 19

What feature of hyposplenism might you see on a blood film of a patient with sickle cell anaemia?

Answer 19

Howell-Jolly bodies - clusters of DNA (pathognomic of splenic dysfunction)

Question 20

Describe the severity of the following types of sickle cell disease:

1. Sickle cell trait
2. Sickle cell anaemia
3. HbSC
4. HbS/beta thalassemia

Answer 20

1. Sickle cell trait - usually asymptomatic
2. Sickle cell anaemia - manifests when HbF decreases and HbS increases (at 6 months age). Severe symptoms
3. HbSC - slightly milder than sickle cell anaemia
4. HbS/beta thalassemia - severity depends on thalassaemia beta chain expression

Question 21

When is sickle cell anaemia usually diagnosed in the UK?

Answer 21

At birth following the Guthrie test

Question 22

At what age does sickle cell disease present and why?

Answer 22

• Presents at 5 months
• Clinical features only manifest when HbF levels drop and HbS levels increase

Question 23

Why do symptoms of sickle cell anaemia in a child differ from sickle cell anaemia in an adult?

Answer 23

Mainly because the distribution of red bone marrow (contains haematopoietic precursors) differs

• Red bone marrow is vascular, metabolically active and susceptible to infarction
• Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia

Hence this is why hand-foot syndrome only occurs in young children

Question 24

How is the pattern of bone pain due to infarction different in adults with sickle cell anaemia compared to children?

Answer 24

• Adults - only happens in axial skeleton
• Infants/Children - can happen anywhere (particular in hands and feet)

Question 25

What age group does hand-foot syndrome affect?

Answer 25

<2 years

Question 26

What is splenic sequestion?

Answer 26

Vaso-occlusion in the spleen leading to acute pooling of blood in the spleen leading to hypovolaemia, shock and death

Question 27

Why does splenic sequestion only occur in children and not older patients?

Answer 27

• As patients with SCD age, numerous splenic infarcts lead to hyposplenism and a small and fibrotic spleen
• Children typically still have function spleens