Paediatric Haematology Flashcards
What are the differences in red blood cells in children?
- site of haematopoiesis varies
- haemoglobin switching - at birth 55-65% is HbF
- difference in red cell structure and metabolism
- larger red blood cells
- higher haematocrit
What is meant by haematocrit?
the ratio of the volume of red blood cells to the total volume of blood
How does the site of haematopoiesis change in children?
- occurs in the yolk sac up to 2 ½ months
- at 1 month, the liver starts producing red cells
- this peaks at 5 months and ends at 9 months
- the spleen starts at around 2 ½ months, peaks at 5 months and ends at 7 months
- the bone marrow starts at 4 ½ months and takes over
What is the purpose of haemoglobin switching?
to bind oxygen with greater affinity so that it can be taken from the mother
What are the 3 different types of embryonic haemoglobin?
Hb Gower-1:
- consists of 2 zeta chains and 2 epsilon chains
Hb Gower-2:
- consists of 2 alpha chains and 2 epsilon chains
Hb Portland:
- consists of 2 zeta chains and 2 gamma chains
What are the embryonic haemoglobin chains?
Which chromosome do they originate from?
zeta:
- originates from chromosome 16
- this codes for the 2 alpha chains
epsilon:
- originates from chromosome 11
- this codes for the 2 beta chains
What happens in haemoglobin switching after 14/40?
Hb Portland and Hb Gower-2 switch to become HbF
this consists of 2 alpha and 2 gamma chains
What happens to haemoglobin switching at the neonatal stage?
Hb F switches to Hb A
this consists of 2 alpha and 2 beta chains
it may also convert to Hb A2
this consists of 2 alpha and 2 delta chains
What is the difference in white blood cell numbers in children and adults?
they have similar numbers of white blood cells
children have higher lymphocyte counts
How does the immune system progress in childhood?
When can a child start making satisfactory immune responses?
- IgG crosses the placenta
- breast milk contains IgA, IgD, IgE, IgG, IgM which provide passive immunity
- antibody production starts between 2/3 - 12 months
- satisfactory immune responses are produced between 6 - 12 months
Why does ABO incompatibility produce less severe haemolytic disease of the newborn than Rhesus group?
most antibodies to A and B antigens on the blood cells are IgM
Why are babies not vaccinated at birth?
for the first 6-12 months of life, the baby receives passive immunity from maternal antibodies
if you were to vaccinate a young baby with a virus, the mother’s antibodies would stick to the virus and try to eliminate it, so the vaccination would not work
How do platelets vary in children?
- adult numbers are reached by 18/40 gestation
- platelets initially larger but they slim down to adult size
- functionally different at birth
- hyporesponsive to certain agonists
- hyperresponsive to vWF
Why is the highest rate of thrombosis seen in neonates compared to all paediatrics?
hyper-responsiveness to vWF enhances the platelet - blood vessel wall interaction
What is haemostasis like at birth?
When does it reach adult values?
coagulation proteins do not cross the placenta effectively
only fibrinogen, FV, FVIII, FXIII are normal at birth
most haemostatic parameters reach adult values by 6 months
Which clotting factors are vitamin K dependent?
Where does the foetus receive its vitamin K from?
FII, FVII, FIX, FX, protein C, protein S
the placental gradient means fetal vitamin K is 10% mother
How can haemorrhagic disease of the newborn be prevented?
What is it?
rare form of bleeding disorder that affects newborns and young infants due to low stores of vitamin K at birth
commonly presents with intracranial haemorrhage and risks of brain damage / death
prevented by routine neonatal vitamin K injection
What maternal medications can exacerbate haemolytic disease of the newborn?
- anti-convulsants - the mother needs oral vitamin K
- warfarin is teratogenic
Which procoagulant proteins are reduced at birth?
- FII
- FVII
- FIX
- FX
- FXI
- FXII
- prekallikrein
- high molecular weight kininogens
Which coagulation inhibitors are there a reduced concentration of at birth?
- antithrombin III
- heparin cofactor 2
- protein C
- protein S
- tissue factor pathway inhibitor (TFPI)
What are other differences present in neonatal haemostasis?
- unique forms of fibrinogen and plasminogen
- raised D-Dimers and vWF
- platelet aggregation differs
What are the congenital reasons for anaemia in childhood?
- haemoglobinopathy - problem with haemoglobin synthesis
- bone marrow failure syndromes
- bone marrow infiltration
- peripheral destruction
- blood loss
What are examples of haemoglobinopathies?
How can they be prevented?
thalassaemia and sickle cell disease
prevented through antenatal screening (before birth, during pregnancy)
What is a haemoglobinopathy?
a hereditary condition involving an abnormality in the structure of haemoglobin
5% of the worldwide population carry an abnormal gene
During haemoglobin switching at the neonatal stage, how can sickle cell or beta thalassaemia arise?
sickle cell:
- single base change resulting in defective beta chain
beta thalassaemia:
- reduced or absent beta chains
What condition is shown here?
sickle cell anaemia
What 3 factors influence the global distribution of haemoglobinopathies?
- malaria benefit
- genetic drift
- population mixing
What can lead to peripheral destruction, resulting in anaemia?
- Rh / ABO or other incompatibility
- infection
- membrane defect - hereditary spherocytosis
- enzyme defect
- G6PD deficiency
- PK deficiency
What type of anaemia results from peripheral destruction?
increased destruction of red blood cells in the peripheral blood without evidence of ineffective erythropoiesis
this is haemolytic anaemia
What is shown here?
hereditary spherocytosis
caused by mutations which lead to defects in RBC membrane proteins
the microspherocyte results from the loss of RBC membrane surface area
What procedures are performed when there is blood loss after birth?
- twin to twin transfusion
- fetomaternal haemorrhage
What are the causes of acquired anaemia in childhood?
- nutritional deficiency - iron, B12, folate
- bone marrow failure
- bone marrow infiltration
- peripheral destruction - haemolysis
- blood loss
What are congenital causes of bleeding and bruising in childhood?
- platelet problem
- clotting factor problem
- connective tissue disorder
What are the acquired causes of bleeding and bruising in childhood?
- trauma
- tumour
- infection (acute - meningococcus or chronic - HIV)
- immune disorder
- primary - immune thrombocytopenia, TTP
- secondary - SLE, ALPS
- bone marrow failure
- drug related
What is meant by epigenetics?
the same child behaves differently in different situations
e.g. in school and at home
this is applied to genes
