10. Paediatric haematology Flashcards
What can lead to one twin becoming anaemic and the other becoming polycythaemia?
Shared placental circulation
What are causes of polycythaemia in foetuses?
Twin-to-twin transfusion, intrauterine hypoxia, placental insufficiency
What are causes of anaemia in foetuses?
Twin-to-twin transfusion; foetal-to-maternal transfusion; parvovirus infection (virus not cleared by immature immune system); haemorrhage from cord or placenta
What are other causes of damage to the foetus (give 5 causes)?
- Irradiation,
- damage by something crossing the placenta (e.g. drugs, chemicals, antibodies);
- anticoagulants (can cause haemorrhage or foetal deformity (e.g. vitamin K if given in the first trimester));
- antibodies can destroy red cells, white cells or platelets;
- substances in breast milk (e.g. a G6PD deficient baby may suffer from haemolysis if their mother eats fava beans).
When does the first mutation that subsequently leads to childhood leukaemia develop?
In utero
Can pre-leukaemic cells spread from one twin to the other?
Yes, pre-leukaemic cells carrying this mutation can even spread from one twin to the other
Leukaemia can develop in utero and manifest in the neonate. What condition is congenital leukaemia particularly common in?
Down syndrome
What is congenital leukaemia sometimes called?
Transient abnormal myelopoiesis
How is congenital leukaemia/ transient abnormal myelopoiesis (TAM) different from leukaemia in older children?
Disease tends to remit spontaneously within the first two months. However it tends to relapse 1-2 years later in about 25% of infants.
What is the capacity of spontaneous remission of congenital leukaemia similar to?
Neuroblastoma
Congenital leukaemia is myeloid with major involvement of which lineage?
Megakaryocyte
What two terms are used to describe defects in the synthesis of globin chains?
Haemoglobinopathies and thalassemias
What is a thalassemia?
A condition resulting from a reduced rate of synthesis of one or more of the globin chains as a result of a genetic defect
What is a haemoglobinopathy?
Refers to a structurally abnormal haemoglobin (NOTE: some consider thalassemia to be a form of haemoglobinopathy)
What are the different times in life that defects in alpha globin chain and beta globin chain occur?
Defects in alpha globin chain and beta globin chains occur at different times in life because alpha globin synthesis begins early in foetal life whereas beta globin synthesis begins late in gestation
What genes are the globin chains controlled by?
The globin chains are controlled by globin genes on chromosome 11 and chromosome 16
What genes does chromosome 11 have?
Chromosome 11 has the beta cluster. It has: beta gene, delta gene, gamma gene, and the locus control region is required for the synthesis of all chains. Epsilon is an embryonic globin gene
What genes does chromosome 16 have?
2x alpha genes, zeta gene - expressed in the embryo
What are normal forms of haemoglobin?
A, A2 and F
What globin chains are associated with haemoglobin A?
alpha2beta2
What period is haemoglobin A mainly present?
Late, foetus, infant, child and adult
What globin chains are associated with haemoglobin A2?
alpha2delta2
What period is haemoglobin A mainly present?
Infant, child and adult
What globin chains are associated with haemoglobin F?
alpha2gamma2
What period is haemoglobin F mainly present?
Foetus and infant
What percentage of total adult haemoglobin should HbA2 be?
<3.5%
Describe how haemoglobin changes throughout foetal life (from conception until 9 months of age)?
There are some specific foetal haemoglobins present in the first 16 weeks from conception (Haemoglobins Gower 1, Gower 2, Portland 1). Then HbF predominates throughout most of foetal life. After around 32 weeks you get a rapid increase in HbA production. At birth, about 1/3 of haemoglobin is HbA, but this rapidly increases after birth. Low levels of haemoglobin A2 are seen after week 30 (?) from conception, and remain at low levels after birth.
What is the difference between sickle cell anaemia (HbSS) and sickle cell disease?
Sickle cell anaemia refers to homozygosity of the HbS gene. Sickle cell disease encompasses homozygous AND heterozygous states associated with sickling.
SCD includes compound heterozygous states such as?
HbSC and HbS/beta thalassemia
What is the pathophysiology of SCD?
- HYPOXIA leads to polymerisation of haemoglobin S leading to crescent shaped red blood cells and blocked blood vessels.
- This tends to occur in post-capillary venules.
- When passing through these venules, red cells tend to elongate.
- If the circulation slows, the cells will begin sickling and becoming adherent to the endothelium which causes obstruction.
- Retrograde capillary obstruction results in arterial obstruction.
- At the beginning of the hypoxic stimulus, the cells may start to become distorted, however, this is reversible once the hypoxic state resolves.
- A lot of the cells that become very sickled will be irreversible.
What are Howell Jolly bodies a feature of?
Howell Jolly bodies are a feature of hyposplenism (e.g. due to splenic infarction)
How does sickle cell trait (HbAS) manifest?
Totally asymptomatic
What is the severity of HbSC in comparison to HbSS?
HbSC causes a sickling disorder that is slightly milder than HbSS
What does the severity of HbS/beta thalassemia depend on?
HbS/beta thalassemia severity depends on whether it is a beta-0 gene (no beta globin production) or beta+ gene (a little bit of beta globin production)
When does sickle cell anaemia start to manifest?
Sickle cell anaemia become manifest as gamma chain production and HbF synthesis DECREASE and HbS production INCREASE. This occurs around 6 months of age.
In the UK when is sickle cell anaemia usually diagnosed and how?
In the UK, sickle cell anaemia is usually diagnosed AT BIRTH (Guthrie test)
Universal neonatal screening must be coordinated with universal antenatal screening. The antenatal screening is based on risk, such as? Why is this important to make the diagnosis at birth?
The antenatal screening is based on risk (e.g. ethnicity, prevalent areas). Making a diagnosis as a neonate allows prevention and anticipation of some of the complications.
Why does sickle cell anaemia in a child differs from the same disease in the adult, regarding the bone marrow?
This is because the distribution of red bone marrow differs. When born, all bone marrow is red, and eventually gets converted to yellow bone by age 7. Red bone marrow is vascular, metabolically active and requires an oxygen supply so it is susceptible to infarction. Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia.
What does red and yellow bone marrow contain?
Red bone marrow is the type of bone marrow that contains haemopoietic precursors with developing red cells and white cells. Yellow marrow is largely fat.
Where does bone pain due to infarction happen in adults and infants/children?
In ADULTS, this will only happen in the central skeleton. In INFANTS and CHILDREN, this can happen all the way down to the fingertips (hand/foot syndrome).
Why does sickle cell anaemia in a child differs from the same disease in the adult, regarding the spleen? And what adverse events in children can this lead to?
Another reason for the difference in clinical manifestation between infant and adult is that the infant still has a functioning spleen. This means that the child can undergo splenic sequestration which is the acute pooling of a large percentage of circulating red cells in the spleen. This can also lead to SEVERE ANAEMIA, SHOCK and DEATH.
