Paediatric Haematology

Question 1

Describe how the site of haematopoiesis varies from foetus –> child

Answer 1

early foetus –> yolk sac

late foetus –> liver and spleen

neonate and child –> bone marrow

Question 2

What haemoglobin switch occurs at birth?

Answer 2

A shift from γ-globin to β-globin gene expression around birth –> switch from foetal (α2γ2; HbF) to adult (α2β2; HbA) Hb production

• 55-65% is HbF at birth
• By 6 months of age the major Hb is HbA

Question 3

Define haematocrit

Answer 3

The ratio of the volume of red blood cells to the total volume of blood.

Question 4

On which chromosome are alpha chains produced?

Answer 4

16

Question 5

On which chromosome are beta, gamma and delta chains produced?

Answer 5

11

Question 6

What is Hb Portland 1?

Answer 6

Hb Portland is a form of Hb existing at low levels during embryonic and foetal life, composed of two zeta chains and two gamma chains.

Question 7

What are the the human embryonic haemoglobins?

Answer 7

Hb Gower 1
Hb Gower 2
Hb Portland 1
Hb Portland 2

Question 8

What are the 2 types of adult Hb?

Answer 8

HbA –> 2 alpha 2 beta

HbA2 –> 2 alpha 2 delta

Question 9

Describe the difference between the affinity of Hb for O2 in foetus vs adult

Answer 9

HbF has a stronger affinity for O2 compared to HbA

Question 10

What is P50?

Answer 10

p50 is the oxygen tension when hemoglobin is 50 % saturated with oxygen.

A lower p50 means stronger binding or higher affinity for oxygen.

Question 11

What are reticulocytes?

Answer 11

Reticulocytes are immature red blood cells (RBCs)

Question 12

What Ig crosses the placenta to give the foetus passive immunity?

Answer 12

IgG

Question 13

What Ig are present in breast milk?

Answer 13

Breast milk has IgA, IgD, IgE, IgM

Question 14

When do children start producing antibodies?

Answer 14

Children start producing antibodies at 2-3 months, and can make a satisfactory immune response by 6 months

Question 15

When are vaccinations carried out? Why?

Answer 15

Vaccinations are carried out at 2-3 months as they are very vulnerable and can carry out a good enough response

Question 16

When do platelets reach adult numbers?

Answer 16

18w gestation

Question 17

How are platelets functionally different at birth?

Answer 17

o Hypo-responsive to certain agonists
o Hyper-responsive to vWF
o Differences balance out

Question 18

Do coagulation factors cross the placenta? Why?

Answer 18

Not effectively, so the foetus will not get any from the mother.

This is important because it reduces likelihood of clots forming within the placenta.

Question 19

What coagulation factors are present at birth?

Answer 19

Only fibrinogen, Factors 5, 8, 13 are normal at birth (remember as 5+8=13), most other parameters reach adult values by 6 months

Question 20

Which form of haemophilia is it possible to detect at birth?

Why?

Answer 20

It is possible to detect Haemophilia A at birth but not B (only 8 is present, not 9)

Question 21

Which coagulation factors are vitamin K dependent?

Answer 21

o	Factor 2
o	Factor 7
o	Factor 9
o	Factor 10
o	Protein C
o	Protein S

Question 22

foetal vitamin K is 10% that of the mother due to..?

Answer 22

Placental gradient

Question 23

What is haemorrhagic disease of the newborn (HDN)?

Answer 23

Vitamin K deficiency-related bleeding - a rare disease with high mortality and morbidity

Question 24

Why are newborns offered a vitamin K injection?

Answer 24

To prevent HDN

Question 25

Which class of drug has been thought to exacerbate vitamin K deficiency in neonates?

Answer 25

AEDs (anti-convulsants)

Question 26

Why is warfarin teratogenic?

Answer 26

Warfarin is teratogenic as it inhibits vitamin K (stands for Wisconsin animal research farm), was used as rat poison to make them bleed

Question 27

Potential causes of congenital anaemia?

Answer 27

* Haemoglobin synthesis problem: haemoglobinopathy * Bone marrow failure syndromes * Bone marrow infiltration * Peripheral destruction * Blood loss

Question 28

Where is the mutation present in sickle cell disease?

Answer 28

single gene mutation on Beta chain causes sickling, sticky cells.

Question 29

What is Rh incompatibility?

Answer 29

A condition that occurs during pregnancy if a woman has Rh-negative blood and her baby has Rh-positive blood. Rh factor is a protein on red blood cells.

Question 30

What is hereditary spherocytosis?

Answer 30

An abnormality of RBCs. The disorder is caused by mutations in genes relating to membrane proteins that allow for the erythrocytes to change shape Normal biconcave RBCs are spherical instead and rupture easily. No central pallor seen as the RBCs are spherical and thus not thinner in the centre.

Question 31

What 2 enzyme deficiencies can lead to peripheral destruction of RBCs?

Answer 31

``` o G6PD deficiency o PK (pyruvate kinase) deficiency ```

Question 32

What is a G6PD deficiency?

Answer 32

G6PD helps red blood cells work. It also protects them from substances in the blood that could harm them. G6PD deficiency is a genetic disorder that most often affects males.

Question 33

What is PK (pyruvate kinase) deficiency?

Answer 33

Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells (haemolytic anaemia).

Question 34

What is twin to twin transfusion?

Answer 34

* Only occurs in monochorionic twin foetuses which share a placenta. The blood circulation becomes shared due to connecting blood vessels within the placenta, allowing blood to pass from one twin to the other * One twin confers RBCs to the other, due to disproportionate blood vessel growth or direction. * The redder twin has too many RBCs, and will need plasma transfusions to dilute the RBCs Fetomaternal haemorrhage – usually not a problem due to high platelets

Question 35

What is the most common cause of acquired childhood anaemia?

Answer 35

Iron deficiency

Question 36

What nutritional deficiencies can lead to acquired childhood anaemia?

Answer 36

iron (most common), B12, folate

Question 37

How can bone marrow failure lead to acquired childhood anaemia?

Answer 37

normal stem cells do not make much blood

Question 38

How can bone marrow infiltration lead to acquired childhood anaemia?

Answer 38

malignancy takes over function and space of bone marrow, storage disorders

Question 39

Congenital causes of bruising and bleeding?

Answer 39

o Platelet problem (inherited) o Clotting factor problem o Connective tissue disorder

Question 40

Acquried causes of bruising and bleeding?

Answer 40

o Trauma: accidental, non-accidental (without good clotting, children are vulnerable) o Tumour o Infection: acute e.g. meningococcus, chronic e.g. HIV o Immune disorder: (primary – immune thrombocytopenia (TTP), secondary – SLE, ALPS o Bone marrow failure o Drug related