Paediatric Haematology: Sickle cell + Thalasaemia Flashcards
What are the general trends in paediatric blood counts compared to an adult?
- Higher WCC
- Higher Neutrophils, lymphocytes (more common reactive lymphocytosis=
In neonates:
higher haemoglobin
Higher MCV
What is congenital leukaemia?
What is the most common type?
What cell lineage is involved and what is the prognosis?
Specific type of neonatal leukaemias within the first months of life
transient abnormal myelopoiesis (TAM) - often with Down’s
–> Myeloid leukaemia with involvement of the megakaryocytic lineage
Usually remits spontaneously and relapses in 1/4 of children 1-2 years later
What chromosomes are the genes for formation of alpha and beta globes (for haemoglobin) located?
alpha: Chromosome 16
Beta: Chromosome 11
What is the makeup of HbA, Hbf and HbA2?
At what time does the HbF gets replaced by adult HbA?
HbA concentrations start to rise during late foetal state/ early newborn phase
What genetic mutation occurs in sickle cell disease and Trait?
How does that change the haemoglobin molecule?
Point Mutation occurs on the ß-globin chain gene
Trait: 1 gene is affected
Disease: both genes are effected
That replaces a charged glutamic acid with an unchgarged valine to form the HbS –> HbS deoxygenates quicker than normal Hbß
What is Haemoglobin C?
A beta-haemoglobin abnormality (similar to sickle cell mutation, but less severe)
At what age does Sickle cell disease usually present?
How is it now usually diagnosed?
Usually clinically manifest after birth (few months), once HbF is replaced
But now usually diagnosed by Guthrie spot/ neonatal heel prick
Why does sickle cell disease usually causes vascular occlusion?
If hypoxic: sickle cells deform and reduce elasticity
–> adhere to vascular endothelium, which disrupts microcirculation
–> intra- and extravascular (spleen) haemolysis
What is hand-foot syndrome?
What age does it usually occur?
Why?
Complication of Sickle cell-disease occurring ages 0-2 years
Often sickening occurs in the red bone marrow, because loads of bloods goes there
In children, there is also red bone marrow that extends to the hands and feet (not in adults) –> Infacction of Bones in Hands and feet –> Dactylitis/ Hand foot syndrome
What are the most common/ important vaso-occulsive events in sickle cell in the first 10 years of life?
+ Splenic sequestration
What is splenic sequestration?
In what age does it occur and why?
- acute pooling of a large percentage of circulating red cells in the spleen
- The spleen enlarges acutely
- The Hb falls acutely and death can occur
- This doesn’t happen in older children and adults because recurrent infarction has left the spleen small and fibrotic
What precautions need to be taken in a child with sickle cell disease and hyposplenism?
Increased risk of infection due to spleen + immature immune system
Vaccinations
- Pneumococcus
- mengincococci, haemophilus influenza
Prophylactic penicillin
What does parvovirus B19 infection lead to in a child with sickle cell disease and hyposplenism?
How Is it managed?
Manifestation
- red cell aplasia (also causes aplasia in normal children, but because of lifespan of 10-20 days (vs usually 120 days) it becomes symptomatic anaemia
Management
- increased awareness for early pick up
- transfusion
Why does a child with sickle cell disease need more folic acid?
- Increased erythropoiesis
- Growth suports
- RBC life span is shorter
What is the management for every Sickle cell disease child ?
- Early diagnosis
- Parental education
- Vaccination
- Penicillin
- Folic acid supplementation
Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count—likely diagnosis?
- Splenic sequestration
- Parvovirus B19 infection
- Folic acid deficiency
- Haemolytic crisis
- Vitamin B12 deficiency
2: Parvovirus B19 infection
A 6-year-old Afro-Caribbean boy presents with chest and abdominal pain; Hb is 63 g/l, MCV 85 fl and blood film shows sickle cells—likely diagnosis?
- Sickle cell trait
- Sickle cell anaemia
- Sickle cell/beta thalassaemia
2: Sickle cell anaemia
It is not sickle cell/ beta thalassaemia as the MCV is normal- in beta-thalassaemia it would be microcytic
What is the clinical management of sickle-cell trait?
Usually nothing needed
Pt. with high ethinic background with high prevalence should be tested before surgery to avoid hypoxia during surgery
Name 5 functions of the spleen
- Removal of senescent of damaged RBC
- Antibody synthesis
- Removal of encapsulated micro-organism
- Removal of antibody-complement coated microorgnaisms
- Removal of Red cells inclusions including malaria parasites
What are the features of Sickle cell on a blood film?
- Anaemaic (Hb 60-80)
- Normocytic
- Increase in reticulocytes
- Abnormal cells: Boat cells, sickle cells, target cells, polychromasia, nucleated RBC
- Features of Hyposplenism: hotel-jolly bodies, Pappenheimer bodies and increased platelets)
What are medical treatments available for children with sickle cell anaemia with recurrent painful crises?
1.Blood transfusion –> to lower part of HbS (acute or recurrent)
Hydroxycarbamide (Hydroxyurea) –> increase in HbF production
What ethinic groups have a higher prevalence of Sickle cell disease/ trait?
- African descent
- Middle eastern
3.
What is the epidemiology of beta-thalassaemia?
- Mediterranean (Cyprus, greece, italy)
- South-east Asia
- India
4.
What are blood count findings of beta-thalassaemia trait?
Usually only Microcytosis
- Reduced rate of ß-chain production –> microcytosis
but - Increased RBC production –> no anaemia
- Usually normal MCHC (can be reduced in IDA)
How is the diagnosis of ß-thalassaemia trait made?
- microcytosis + increase of HbA2
What are the different forms of Beta-thalassaemia major that can be present?
ß-globin mutations can lead to absence of ß-chain formation ß0 or severely reduced formation (ß+)
When does beta-thalassaemia major usually clinically present?
In first 3-6 months of life (due to reduction of HbF)
But shoulle be picked up by Heel prick test
What are the clinical effects of poorly treated thalasseamia major?
- Anaemia –> heart failure, growth retardation
- Increased Erythropoietic drive –> bone expansion, hepatic-splenomegaly
- Iron overload –> heart failure, gonadal failure
What is the prognosis and clinical management of beta-thalassaemia?
Without treatment life expectancy is only a few years
- Regular Blood transfusions
- Iron chelation
- Curative: BM transplant in young children not yet iron overloaded
Summarise the different forms of alpha-thalassaemia and their prognosis
Overall four alpha genes
1. Deletion of 1-2:no significance for individual, might be significant for pregnancy if both partners
- 3 alpha chains deleted: haemoglobin h disease, –> microcytosis + hepato-splenomegaly. viable, not clinically severe enough to justify termination
- 4 alpha-chains deleted: not viable and death in utero or shortly after birth (Barts hydrops fetalis)
