Haem meded - haemoglobinopathies - Basically Haem 15: Paediatric Haem Flashcards
What are haemoglobinopathies? + how are they diagnosed?
Genetic disorders of globin chain synthesis
Diagnosis made with Hb electrophoresis
What are the different types of human haemoglobin?
HbF (α2ɣ2) – foetus, infant
HbA (α2β2) – late foetus, infant, child and adult
HbA2 (α2δ2) – infant, child and adult
What are some examples of haemoglobinopathies?
Thalassaemia, sickle cell disease
What is β-thalassaemia + where is the gene found? categorisation?
Reduced synthesis of β globin chain (Chromosome 11)
Major (homozygous), intermedia and minor (heterozygous)
What are the key features of major, intermedia and minor β-thalassaemia?
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
How is β-thalassaemia diagnosed??
Diagnosed with high performance liquid chromatography
What does mx of β-thalassaemia involve??
Regular blood transfusions, iron chelation, folate supplementation
When are the different chains of Hb produced?
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)
What is α-thalassaemia? + where is it found + how can it be categorised?
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
What are the different features of the different types of α-thalassaemia?
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
Mx of α-thalassaemia?
Regular blood transfusions, iron chelation, folate supplementation
What condtion (as well as α-thalassaemia) can cause functional hyposplenism?
Coeliac
What is the pathophysiology of Sickle cell disease? What are the different
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)
What is the main clinical features of sickle cell disease?
Haemolytic crisis,
Sequestration crisis
Aplastic crisis
Infection (Streptococcus pneumoniae – sepsis, Salmonella – osteomyelitis THIS IS THE MAIN ONE TO BE AWARE OF)
What is a sequestration crisis as seen in sickle cell?
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
What is an aplastic crisis as seen in sickle cell disease + cause? Key ix finding if this is happening?
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
Ix of sickle cell disease?
Peripheral blood smear - Sickle cells
Sickle solubility test is postive in HbSS and HbAS
Mx of sickle cell disease?
vaccination, folate supplementation, hydroxyurea (IMPORTANT), supportive for acute crisis
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
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
Mohammed is a 4-year-old boy who was born in Bangladesh
He presents to your pediatric clinic. What is the likely diagnosis?
Beta Thalassemia - Problem w/ globin chain hence causes BM to become hyperplastic to drive erythropoesis
This causes raised BM expansion (even in maxilla) + osteoporosis
What is the best investigation to diagnose beta thalassaemia?
High performance liquid chromatography
What are some of the clinical features of Beta thalassaemia Major ?
Bossing of facial bones
Hepatosplenomegaly
Iron overload- heart/liver failure
Growth retardation
How does acute chest syndrome present + cxr?
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.
