HAEM: Paediatric haematology

Question 1

List 3 causes of polycythaemia in the foetus.

Answer 1

• Twin-to-twin transfusion
• Intrauterine hypoxia
• Placental insufficiency

Question 2

X How do FBC findings differ between foetus and adult?

Answer 2

Newborn babies, in contrast to adults, have:

1. A higher Hb
2. A lower WBC
3. Smaller red blood cells
4. The same percentage of haemoglobin F

Question 3

List 3 causes of foetal anaemia.

Answer 3

• Twin-to-twin or Foetal-to-maternal (rare) transfusion
• Parvovirus infection (virus not cleared by immature immune system)
• Haemorrhage from cord or placenta

Question 4

What happens to the baby if it is G6PD deficient and the mother eats fava beans?

Answer 4

Haemolysis in the baby if breastfeeding

Question 5

Which anticoagulant can cause foetal haemorrhage or deformity in the first trimester?

Answer 5

Vitamin K

Question 6

Where does the first leukaemia occur in a child?

Answer 6

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)

Question 7

Which condition is congenital leukaemia more common in? What is it aka here?

Answer 7

Congenital leukaemia is particularly common in Down syndrome

AKA: transient abnormal myelopoiesis / TAM

Question 8

What type of leukaemia is TAM? What is the prognosis?

Answer 8

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

Question 9

What type of cell is shown here?

Answer 9

Megakaryocyte in circulation

Question 10

What is the definition of haemoglobinopathy?

Answer 10

Structurally abnormal hb (N.B. some think thalassemia a form of haemoglobinopathy)

Question 11

Briefly, what is the cause of thalassaemia?

Answer 11

Resulting from reduced rate of synthesis of ≥1 globin chain as a result of a genetic defect

Question 12

Where are genes for alpha and beta globin found?

Answer 12

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)

Question 13

How does type of Hb change from in utero to infancy?

Answer 13

• 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 1/3^rd of haemoglobin is HbA, but this rapidly increases after birth

Question 14

What is seen by blue and red?

Answer 14

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.

Question 15

What globin chains are responsible for coding Hb A, A2 and F? When is each present?

Answer 15

Question 16

What are the types of homozygous and heterozygous SCD?

Answer 16

Homozygous states = HbSS

Heterozygous states = HbSC (sickle cell trait), HbS/b-thal

Question 17

What are Howell-Jolly bodies a feature of?

Answer 17

Hyposplenism

Question 18

What is the pathophysiology of sickling and its complications in SCD?

Answer 18

(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

Question 19

Question 20

What does severity of sickle cell anaemia in HbS/b-thal depend on?

Answer 20

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)

Question 21

When does SC anaemia usually present and why?

Answer 21

Sickle cell anaemia manifests around 6 months of age as…

• Gamma chain production and HbF synthesis DECREASE
• HbS production INCREASE

Question 22

When is SCA usually diagnosed in the UK?

Answer 22

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

Question 23

How does distribution of red bone marrow differ in children and adults? What is the significance of this for SCA?

Answer 23

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

Question 24

How does the spleen differ between children and adults with SCA? What is the significance of this?

Answer 24

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

Question 25

Answer 25

Hyposplenism

Question 26

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

Answer 26

Question 27

Susceptibility to what type of infection in the first decade in SCA? What other infections are these childre an risk of?

Answer 27

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

Question 28

Answer 28

PV B19

Question 29

Answer 29

SCD

Question 30

Why do children with SCA have increased folic acid demands?

Answer 30

Due to: * Hyperplastic erythropoiesis * Growth spurts * Red cell lifespan is shorted so anaemia can rapidly worsen

Question 31

What is the cause of beta-thalassaemia?

Answer 31

Condition related to reduced synthesis of beta globin chain (and so HbA)

Question 32

What is the inheritance of beta-thal?

Answer 32

Question 33

When does beta-thal manifest?

Answer 33

* 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

Question 34

What is the difference between beta thal major and intermedia?

Answer 34

Blood has no HbA in major; blood has some HbA in intermedia

Question 35

What are the types of beta-thalassaemia?

Answer 35

* **bb** = *Normal* * **b****^thal****b** = *Beta thal **trait** / heterozygosity =* Harmless but genetically important * **b****^thal****b****^thal***B= eta thal**major** / homozygosity =* Severe anaemia = fatal without transfusions * **b****^thal****b****^thal**= *Beta thal**intermediate** / homozygosity = ‘*+’ forms of beta (instead of ‘0’)

Question 36

What are 3 clinical features of poorly treated thalassaemia major?

Answer 36

* **Anaemia** --\> heart failure, growth retardation * **Erythropoietic drive** --\> bone expansion, hepatomegaly, splenomegaly * **Iron overload** --\> heart failure, gonadal failure

Question 37

What are the principles of treatment for beta thalassaemia major?

Answer 37

* Accurate diagnosis and family counselling * Blood transfusion (± iron chelation --\> desferrioxamine, deferiprone)

Question 38

Name a haemolytic anaemia in infancy which is not inherited.

Answer 38

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)

Question 39

Answer 39

A A is more common than B

Question 40

List 3 inherited haemolytic anaemias.

Answer 40

* **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)

Question 41

Is G6PDD more common is males or females and why?

Answer 41

G6PDD = X-linked (recessive) so more common in males

Question 42

What questions should you ask if you suspect haemolytic anaemia?

Answer 42

* 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?

Question 43

Is the anaemia in SCA purely due to haemolysis?

Answer 43

_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

Question 44

* 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:

Answer 44

Condition resulting from **oxidant damage in G6PD** deficiency. Contracted red cells seen. ## Footnote *(RBCs are not perfectly round, so more likely G6PDD than HS)*

Question 45

List 3 triggers of haemolysis in G6PD.

Answer 45

* Infections (? UTI) * Drugs (? anti-emetic) * Naphthalene * Fava beans (broad beans)

Question 46

What are the two main types of autoimmune haemolytic anaemias?

Answer 46

​Autoimmune haemolytic anaemia * Spherocytosis * Positive DAT (Coombs' test) Haemolytic uraemic syndrome: * Haemolysis * Uraemia

Question 47

What is the pathogenesis of MAHA?

Answer 47

Red cells are damaged in capillaries forming small angular fragments and micro-spherocytes

Question 48

What are the most common disorders of coagulation?

Answer 48

* **Least**-rare (i.e. common) defects: * Haemophilia A (F8) * Haemophilia B (F9) * Von Willebrand disease

Question 49

How does haemophilia A and B present?

Answer 49

* Bleeding following circumcision * Haemarthroses when starting to walk * Bruises * Post-traumatic bleeding

Question 50

What are the differentials for haemophilia A/B?

Answer 50

* Inherited thrombocytopaenia or platelet functional defect * Acquired defects of coagulation (e.g. ITP, acute leukaemia) * Non-accidental injury * Henoch-Schönlein purpura

Question 51

What