Paediatric Haematology Flashcards
What are the differences between children and adult haematology?
- Range of diseases differs from adults (infections and neoplasia)
- Inherited conditions tend to present in childhood (e.g. sickle cell anaemia)
- Rapid growth → predispose to nutrient deficiency (e.g. iron deficiency, folic acid deficiency)
- Children are more likely to respond to infections with lymphocytosis than adults
- Reactive lymphocytes are more common in children because of frequent encounters with new infections
- Growth retardation can occur with illness or due to its treatment (i.e. old ALL spinal irradiation treatment)
- Pubertal failure / development of 2nd sexual characteristics from illness or treatment (e.g. b-thalassemia major→iron overload→endocrine dysfunction)
What would you find in neonatal haematology?
- Normal ranges for red and white cell variable are different in neonates
- Neonates have high WCC, neutrophils, lymphocytes, Hb and MCV
- Neonates have a higher percentage of HbF → disorders of beta globin genes are less likely to manifest
- The enzyme levels within RBCs is different (e.g. they have ~50% the G6PD concentration of an adult)
- Exposure to noxious stimuli in utero can lead to haematological abnormalities at birth
- The process of birth itself may also damage the neonate
What causes polycythaemia in the fetus?
- Twin-to-twin transfusion
- Intrauterine hypoxia
- Placental insufficiency
What causes anaemia in the foetus?
- Twin-to-twin or Foetal-to-maternal (rare) transfusion
- Parvovirus infection (virus not cleared by immature immune system)
- Haemorrhage from cord or placenta
What are the other causes of damage to the foetus/neonate?
- Irradiation
- Damage by something crossing the placenta (e.g. drugs, chemicals, antibodies)
- Anticoagulants (→ 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. G6PDD-baby may suffer from haemolysis if mother eats fava beans)
When does the first mutation in leukaemia occur?
The first mutation that subsequently leads to childhood leukaemia often occurs in utero (pre-leukaemic cells carrying this mutation can even spread from one twin to the other)
In who is congenital leukaemia common in?
- Congenital leukaemia is particularly common in Down syndrome (AKA: transient abnormal myelopoiesis / TAM)
How does congenital leukaemia progress?
- This is different from leukaemia in older children (TAM is a myeloid leukaemia)
- This disease tends to remit spontaneously within the first 2 months of life
- However, it tends to relapse 1-2 years later in about 25% of infants
- The capacity for spontaneous remission is similar to neuroblastoma
Small megakaryocytic in the circulation and eryhtroblatss
A) A higher Hb
Define thalassaemia and haemoglobinopathy.
- Defects in the globin chain
- Thalassemia → resulting from reduced rate of synthesis of ≥1 globin chain as a result of a genetic defect
- Haemoglobinopathy → structurally abnormal hb (N.B. some think thalassemia a form of haemoglobinopathy)
Describe where the globin chain sites lie in the chromosomes
- The globin chains are controlled by globin genes on chromosome 11 and chromosome 16
- Chromosome 11 (beta cluster) = deletion of LCRB → reduced downstream globin expression:
- Beta, delta, gamma gene - B, D, G
- The locus control region is required for the synthesis of all chains
- Epsilon is an embryonic globin gene
- Chromosome 16 (alpha cluster):
- Alpha 1 and alpha 2 gene (HbA2 = <3.5% of total adult Hb)
- Zeta gene (expressed in the embryo)
- Chromosome 11 (beta cluster) = deletion of LCRB → reduced downstream globin expression:
When does Haemoglobin A,A2 and F get produced?
- 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
- Hb in utero (see graph below)
- Specific foetal haemoglobins are present in the first 16 weeks → HbF predominates
- After around 32 weeks you get a rapid increase in HbA production
- At birth, about 1/3rd of haemoglobin is HbA, but this rapidly increases after birth
What are the types of sickle cell?
- Sickle cell disease refers to pathological signs and symptoms of sickling red blood cells; this includes…
- Homozygous states = HbSS
- Heterozygous states = HbSC (sickle cell trait), HbS/b-thal
What is the pathophysiology of vascular obstruction in SCA?
- Pathophysiology – Howell-Jolly bodies can feature as a feature of hyposplenism
- (1) Hypoxia → polymerisation of haemoglobin S → crescent shaped RBCs and blocked blood vessels
- Occurs in post-capillary venules (when passing through these venules, red cells tend to elongate)
- This is reversible if the hypoxic state is resolved (unless the cells are very sickled)
- (2) If circulation slows, the cells sickle and become adherent to the endothelium which causes obstruction
- (3) Retrograde capillary obstruction → arterial obstruction
- (1) Hypoxia → polymerisation of haemoglobin S → crescent shaped RBCs and blocked blood vessels
- Anaemias
- Howell-jolli bodies
- Sickle cells
What is sickle cell trait
What is sickle cell anaemia?
What is sickle cell/haemoglobin C?
What is sickle cell/beta thalassaemia?
Why does sickle cell anaemia not manifest at birth?
- Sickle cell anaemia manifests around 6 months of age as…
- Gamma chain production and HbF synthesis DECREASE
- HbS production INCREASE
How is sickle cell anaemia diagnosed at birth?
Guthrie spot
What are the implication of making SCA diagnosis in a neonate?
Parents ask why condition not predicted?
- Universal neonatal screening must be coordinated with universal antenatal screening
- Antenatal screening is based on risk (e.g. ethnicity, prevalent areas) → Family Origins Questionnaire:
Making a diagnosis as a neonate allows prevention and anticipation of some of the complications
Why is it advantageous to diagnose SCA at birth?
•Some of the complications can be prevented and others can be anticipated and their effects ameliorated
How does sickle cell symptoms differ in adults vs children?
- Different distributions of red bone marrow:
- Adult haematopoietic BM = restricted to axial skeleton
- Child haematopoietic BM = axial skeleton + extends to bones of hands and feet
- Hence, why children can get the hand-foot syndrome (swollen hands and feet)
- Bone marrow types:
- Yellow BM is largely fat
- Red BM produces haematopoietic precursors with developing RBCs and white cell and is vascular, metabolically active and requires an oxygen supply, so it is susceptible to infarction
- Different spleen types:
- Adult / older-child spleen – spleen is small and fibrotic from recurrent infarction
- Suffer from more chance of sequalae of hyposplenism (i.e. pneumococcal infection)
- Child spleen – still has a functioning spleen
- Children can undergo splenic sequestration which is the acute pooling of a large percentage of circulating red cells in the spleen → SEVERE ANAEMIA, SHOCK and DEATH
- Parents should be taught how to palpate the spleen and to seek medical attention if needed
- Blood transfusion required
- Adult / older-child spleen – spleen is small and fibrotic from recurrent infarction
The hand-foot syndrome
When do we tend to see splenic changes and bactareamia?
Hyposplenism
Parvovirus B19 infection
Sickle cell anaemia
No sickle cells in blood film in SCT
Microcytosis in heterozygous
What is the genetics of beta thalassaemia trait??
What is the genetics of beta thalassaemia?
- Condition resulting from oxidant damage in G6PD deficiency
HUS
Haemophilia A and B
Haemophilia A
