HAEM: Paediatric haematology Flashcards
List 3 causes of polycythaemia in the foetus.
- Twin-to-twin transfusion
- Intrauterine hypoxia
- Placental insufficiency
X How do FBC findings differ between foetus and adult?
Newborn babies, in contrast to adults, have:
- A higher Hb
- A lower WBC
- Smaller red blood cells
- The same percentage of haemoglobin F
List 3 causes of foetal anaemia.
- Twin-to-twin or Foetal-to-maternal (rare) transfusion
- Parvovirus infection (virus not cleared by immature immune system)
- Haemorrhage from cord or placenta
What happens to the baby if it is G6PD deficient and the mother eats fava beans?
Haemolysis in the baby if breastfeeding
Which anticoagulant can cause foetal haemorrhage or deformity in the first trimester?
Vitamin K
Where does the first leukaemia occur in a child?
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)
Which condition is congenital leukaemia more common in? What is it aka here?
Congenital leukaemia is particularly common in Down syndrome
AKA: transient abnormal myelopoiesis / TAM
What type of leukaemia is TAM? What is the prognosis?
TAM is a myeloid leukaemia. It is different from leukaemia in older children.
- Tends to remit spontaneously within the first 2 months of life
- But tends to relapse 1-2 years later in about 25% of infants
- The capacity for spontaneous remission is similar to neuroblastoma
What type of cell is shown here?
Megakaryocyte in circulation
What is the definition of haemoglobinopathy?
Structurally abnormal hb (N.B. some think thalassemia a form of haemoglobinopathy)
Briefly, what is the cause of thalassaemia?
Resulting from reduced rate of synthesis of ≥1 globin chain as a result of a genetic defect
Where are genes for alpha and beta globin found?
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)
How does type of Hb change from in utero to infancy?
- Specific foetal haemoglobins are present in the first 16 weeks à 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 is seen by blue and red?
Red - sickle cell
Blue - cells which look like they are about to sickle
Howell Jolly bodies also seen and anaemia as the cells are very far apart.
What globin chains are responsible for coding Hb A, A2 and F? When is each present?
What are the types of homozygous and heterozygous SCD?
Homozygous states = HbSS
Heterozygous states = HbSC (sickle cell trait), HbS/b-thal
What are Howell-Jolly bodies a feature of?
Hyposplenism
What is the pathophysiology of sickling and its complications in SCD?
(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
What does severity of sickle cell anaemia in HbS/b-thal depend on?
HbS/b-thal severity depends on whether it is a:
- Beta-0 gene (no beta globin production)
- Beta+ gene (a little bit of beta globin production)
When does SC anaemia usually present and why?
Sickle cell anaemia manifests around 6 months of age as…
- Gamma chain production and HbF synthesis DECREASE
- HbS production INCREASE
When is SCA usually diagnosed in the UK?
AT BIRTH (Guthrie spot test)
- 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
How does distribution of red bone marrow differ in children and adults? What is the significance of this for SCA?
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)
- NB: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
How does the spleen differ between children and adults with SCA? What is the significance of this?
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
Hyposplenism
Complications of SCA and when they occur:
- Hand-foot syndrome tends to occur in the first 2 years of life
- Acute chest syndrome is caused by infarction in the ribs and lungs
- Sickle cell anaemia is one of the MOST COMMON causes of stroke in childhood
Susceptibility to what type of infection in the first decade in SCA? What other infections are these childre an risk of?
There is a susceptibility to bacteraemia at younger ages irrespective of hyposplenism
Children are particularly vulnerable to pneumococcus and parvovirus (they have not encountered them before)
- Parvovirus can cause aplastic anaemia in sickle cell anaemia
- Pneumococcal infection is often FATAL in babies with sickle cell anaemia, but this can be prevented with a combination of vaccination and penicillin
PV B19
SCD
Why do children with SCA have increased folic acid demands?
Due to:
- Hyperplastic erythropoiesis
- Growth spurts
- Red cell lifespan is shorted so anaemia can rapidly worsen
What is the cause of beta-thalassaemia?
Condition related to reduced synthesis of beta globin chain (and so HbA)
What is the inheritance of beta-thal?
When does beta-thal manifest?
- Manifest after the first 3-6m of life because of decline of synthesis of HbF and the increased production of HbA
- However, it can be suspected at birth through the Guthrie spot test
What is the difference between beta thal major and intermedia?
Blood has no HbA in major; blood has some HbA in intermedia
What are the types of beta-thalassaemia?
- bb = Normal
- bthalb = Beta thal trait / heterozygosity = Harmless but genetically important
- bthalbthalB= eta thalmajor / homozygosity = Severe anaemia = fatal without transfusions
- bthalbthal= Beta thalintermediate / homozygosity = ‘+’ forms of beta (instead of ‘0’)
What are 3 clinical features of poorly treated thalassaemia major?
- Anaemia –> heart failure, growth retardation
- Erythropoietic drive –> bone expansion, hepatomegaly, splenomegaly
- Iron overload –> heart failure, gonadal failure
What are the principles of treatment for beta thalassaemia major?
- Accurate diagnosis and family counselling
- Blood transfusion (± iron chelation –> desferrioxamine, deferiprone)
Name a haemolytic anaemia in infancy which is not inherited.
Most cases of congenital haemolytic anaemia are inherited however, some are not
e.g. transplacental passage of maternal antibodies can cause haemolytic disease of the newborn (usually due to ABO and RhD antibodies)
A
A is more common than B
List 3 inherited haemolytic anaemias.
- Red cell membrane = hereditary spherocytosis/eliptocytosis
- Haemoglobin molecule = sickle cell anaemia
- Glycolytic pathway enzymes = pyruvate kinase deficiency (provide energy to cell)
- Pentose-phosphate shunt = G6PD deficiency (protect cell from oxidant damage)
Is G6PDD more common is males or females and why?
G6PDD = X-linked (recessive) so more common in males
What questions should you ask if you suspect haemolytic anaemia?
- Anaemia present?
- Evidence of increase red cell turnover? (e.g. jaundice, splenomegaly, increased unconjugated bilirubin)
- Evidence of increased red cell production? (e.g. increased reticulocyte count, bone expansion)
- Abnormal red cells?
Is the anaemia in SCA purely due to haemolysis?
NOT totally due to haemolysis alone
HbS is a low-affinity Hb meaning that it more readily releases O2 to tissues, so the EPO-drive is lower which results in anaemia
- 7-year-old Afro-Caribbean boy had abdominal pain and urinary tract symptoms; given anti-emetic by his GP
- Three days later he was noted to have yellow eyes and was brought to the hospital
- WBC 10.9 × 109/l, Hb 58 g/l, MCV 100 fl, platelet count 275 × 109/l
- Blood film:
Condition resulting from oxidant damage in G6PD deficiency. Contracted red cells seen.
(RBCs are not perfectly round, so more likely G6PDD than HS)
List 3 triggers of haemolysis in G6PD.
- Infections (? UTI)
- Drugs (? anti-emetic)
- Naphthalene
- Fava beans (broad beans)
What are the two main types of autoimmune haemolytic anaemias?
Autoimmune haemolytic anaemia
- Spherocytosis
- Positive DAT (Coombs’ test)
Haemolytic uraemic syndrome:
- Haemolysis
- Uraemia
What is the pathogenesis of MAHA?
Red cells are damaged in capillaries forming small angular fragments and micro-spherocytes
What are the most common disorders of coagulation?
-
Least-rare (i.e. common) defects:
- Haemophilia A (F8)
- Haemophilia B (F9)
- Von Willebrand disease
How does haemophilia A and B present?
- Bleeding following circumcision
- Haemarthroses when starting to walk
- Bruises
- Post-traumatic bleeding
What are the differentials for haemophilia A/B?
- Inherited thrombocytopaenia or platelet functional defect
- Acquired defects of coagulation (e.g. ITP, acute leukaemia)
- Non-accidental injury
- Henoch-Schönlein purpura
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