Haem meded - haemoglobinopathies - Basically Haem 15: Paediatric Haem

Question 1

What are haemoglobinopathies? + how are they diagnosed?

Answer 1

Genetic disorders of globin chain synthesis

Diagnosis made with Hb electrophoresis

Question 2

What are the different types of human haemoglobin?

Answer 2

HbF (α2ɣ2) – foetus, infant
HbA (α2β2) – late foetus, infant, child and adult
HbA2 (α2δ2) – infant, child and adult

Question 3

What are some examples of haemoglobinopathies?

Answer 3

Thalassaemia, sickle cell disease

Question 4

What is β-thalassaemia + where is the gene found? categorisation?

Answer 4

Reduced synthesis of β globin chain (Chromosome 11)

Major (homozygous), intermedia and minor (heterozygous)

Question 5

What are the key features of major, intermedia and minor β-thalassaemia?

Answer 5

Major – severe anaemia requiring regular blood transfusions (defect in both copies of B-globin)

Intermedia – genetically complex, moderate reduction in β globin chain production

Minor – benign but important genetically (defect in one copies of B-globin) only really presents after bouts of illness

Question 6

How is β-thalassaemia diagnosed??

Answer 6

Diagnosed with high performance liquid chromatography

Question 7

What does mx of β-thalassaemia involve??

Answer 7

Regular blood transfusions, iron chelation, folate supplementation

Question 8

When are the different chains of Hb produced?

Answer 8

α - in utero and throughout life

β - low levels in utero rises after 6m

δ - High in utero drops after birth esp after 6m (as β rises)

Hence first few months of life you still have predominantly HbF (α2ɣ2) + (some HbA)

Question 9

What is α-thalassaemia? + where is it found + how can it be categorised?

Answer 9

Reduced synthesis of α globin chain (Chromosome 16)

Hb Barts (x4), HbH (x3), trait (x2), silent (x1) - based on how many of α-globin’s 4 genes for is affected

Question 10

What are the different features of the different types of α-thalassaemia?

Answer 10

Hb Barts – fatal in utero, hydrops foetalis (IMPORTANT)

HbH – severe anaemia in childhood (can lead to functional hyposplenism as spleen uses up so much of its function - splenectomy / spleen atrophy is seen), hepatosplenomegaly

Trait – mild anaemia

Silent – asymptomatic

Question 11

Mx of α-thalassaemia?

Answer 11

Regular blood transfusions, iron chelation, folate supplementation

Question 12

What condtion (as well as α-thalassaemia) can cause functional hyposplenism?

Answer 12

Coeliac

Question 13

What is the pathophysiology of Sickle cell disease? What are the different

Answer 13

Autosomal recessive (Glutamate -> Valine) mutation at codon 6 on the β globin chain -> HbS (hydrophobic part in sickle wall causes sickling)

HbSS (2 copies), HbAS (1 normal a-chain, 1 sickle), HbSC, HbSβ (sickle x thalassaemia crossover)

Question 14

What is the main clinical features of sickle cell disease?

Answer 14

Haemolytic crisis,

Sequestration crisis

Aplastic crisis

Infection (Streptococcus pneumoniae – sepsis, Salmonella – osteomyelitis THIS IS THE MAIN ONE TO BE AWARE OF)

Question 15

What is a sequestration crisis as seen in sickle cell?

Answer 15

This crisis occurs when splenic vaso-occlusion, caused by an area of sickled cells, causes a large percentage of total blood volume to become trapped within the spleen

Question 16

What is an aplastic crisis as seen in sickle cell disease + cause? Key ix finding if this is happening?

Answer 16

Caused by PARVOVIRUS infection

Virus can infect erythroid cells in BM and cause arrest in maturation - in someone w/ normal RBC survival it has little impact on Hb conc

In sickle cell (shortened RBC survival = 5-7d) -> this can cause a dangerously low Hb (aplastic crisis)

KEY FINDING = ZERO RETICULOCYTES

Question 17

Ix of sickle cell disease?

Answer 17

Peripheral blood smear - Sickle cells

Sickle solubility test is postive in HbSS and HbAS

Question 18

Mx of sickle cell disease?

Answer 18

vaccination, folate supplementation, hydroxyurea (IMPORTANT), supportive for acute crisis

Question 19

Which of these is true about alpha thalassemia?

Caused by a defect on Chr 11
There is increased destruction of beta globin chains
Decreased gamma-globin chains
4 mutated genes can lead to hydrops fetalis
Increased production of alpha globin chains

Answer 19

4 mutated genes can lead to hydrops fetalis

• Caused by defect on chr 16! (b-thal = chr 11)
• Reduced synthesis of α globin chain is MoA

Question 20

Mohammed is a 4-year-old boy who was born in Bangladesh

He presents to your pediatric clinic. What is the likely diagnosis?

Answer 20

Beta Thalassemia - Problem w/ globin chain hence causes BM to become hyperplastic to drive erythropoesis

This causes raised BM expansion (even in maxilla) + osteoporosis

Question 21

What is the best investigation to diagnose beta thalassaemia?

Answer 21

High performance liquid chromatography

Question 22

What are some of the clinical features of Beta thalassaemia Major ?

Answer 22

Bossing of facial bones
Hepatosplenomegaly
Iron overload- heart/liver failure
Growth retardation

Question 23

How does acute chest syndrome present + cxr?

Answer 23

This is seen in sickle cell pts and typically presents with a mixture of fever, dyspnoea, chest pain, hypoxia and cough.

A chest x-ray will show pulmonary infiltrates.