Paediatric Haematology: Sickle cell + Thalasaemia

Question 1

What are the general trends in paediatric blood counts compared to an adult?

Answer 1

1. Higher WCC
2. Higher Neutrophils, lymphocytes (more common reactive lymphocytosis=

In neonates:
higher haemoglobin
Higher MCV

Question 1

What is congenital leukaemia?

What is the most common type?
What cell lineage is involved and what is the prognosis?

Answer 1

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

Question 2

What chromosomes are the genes for formation of alpha and beta globes (for haemoglobin) located?

Answer 2

alpha: Chromosome 16

Beta: Chromosome 11

Question 3

What is the makeup of HbA, Hbf and HbA2?

Answer 3

Question 4

At what time does the HbF gets replaced by adult HbA?

Answer 4

HbA concentrations start to rise during late foetal state/ early newborn phase

Question 5

What genetic mutation occurs in sickle cell disease and Trait?

How does that change the haemoglobin molecule?

Answer 5

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

Question 6

What is Haemoglobin C?

Answer 6

A beta-haemoglobin abnormality (similar to sickle cell mutation, but less severe)

Question 7

At what age does Sickle cell disease usually present?

How is it now usually diagnosed?

Answer 7

Usually clinically manifest after birth (few months), once HbF is replaced

But now usually diagnosed by Guthrie spot/ neonatal heel prick

Question 8

Why does sickle cell disease usually causes vascular occlusion?

Answer 8

If hypoxic: sickle cells deform and reduce elasticity
–> adhere to vascular endothelium, which disrupts microcirculation

–> intra- and extravascular (spleen) haemolysis

Question 9

What is hand-foot syndrome?

What age does it usually occur?
Why?

Answer 9

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

Question 10

What are the most common/ important vaso-occulsive events in sickle cell in the first 10 years of life?

Answer 10

+ Splenic sequestration

Question 11

What is splenic sequestration?
In what age does it occur and why?

Answer 11

• 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

Question 12

What precautions need to be taken in a child with sickle cell disease and hyposplenism?

Answer 12

Increased risk of infection due to spleen + immature immune system

Vaccinations
- Pneumococcus
- mengincococci, haemophilus influenza

Prophylactic penicillin

Question 13

What does parvovirus B19 infection lead to in a child with sickle cell disease and hyposplenism?

How Is it managed?

Answer 13

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

Question 14

Why does a child with sickle cell disease need more folic acid?

Answer 14

1. Increased erythropoiesis
2. Growth suports
3. RBC life span is shorter

Question 15

What is the management for every Sickle cell disease child ?

Answer 15

1. Early diagnosis
2. Parental education
3. Vaccination
4. Penicillin
5. Folic acid supplementation

Question 16

Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count—likely diagnosis?

1. Splenic sequestration
2. Parvovirus B19 infection
3. Folic acid deficiency
4. Haemolytic crisis
5. Vitamin B12 deficiency

Answer 16

2: Parvovirus B19 infection

Question 17

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?

1. Sickle cell trait
2. Sickle cell anaemia
3. Sickle cell/beta thalassaemia

Answer 17

2: Sickle cell anaemia

It is not sickle cell/ beta thalassaemia as the MCV is normal- in beta-thalassaemia it would be microcytic

Question 18

What is the clinical management of sickle-cell trait?

Answer 18

Usually nothing needed

Pt. with high ethinic background with high prevalence should be tested before surgery to avoid hypoxia during surgery

Question 19

Name 5 functions of the spleen

Answer 19

1. Removal of senescent of damaged RBC
2. Antibody synthesis
3. Removal of encapsulated micro-organism
4. Removal of antibody-complement coated microorgnaisms
5. Removal of Red cells inclusions including malaria parasites

Question 20

What are the features of Sickle cell on a blood film?

Answer 20

1. Anaemaic (Hb 60-80)
2. Normocytic
3. Increase in reticulocytes
4. Abnormal cells: Boat cells, sickle cells, target cells, polychromasia, nucleated RBC
5. Features of Hyposplenism: hotel-jolly bodies, Pappenheimer bodies and increased platelets)

Question 21

What are medical treatments available for children with sickle cell anaemia with recurrent painful crises?

Answer 21

1.Blood transfusion –> to lower part of HbS (acute or recurrent)

Hydroxycarbamide (Hydroxyurea) –> increase in HbF production

Question 22

What ethinic groups have a higher prevalence of Sickle cell disease/ trait?

Answer 22

1. African descent
2. Middle eastern
   3.

Question 23

What is the epidemiology of beta-thalassaemia?

Answer 23

1. Mediterranean (Cyprus, greece, italy)
2. South-east Asia
3. India
   4.

Question 24

What are blood count findings of beta-thalassaemia trait?

Answer 24

Usually only Microcytosis

1. Reduced rate of ß-chain production –> microcytosis
   but
2. Increased RBC production –> no anaemia
3. Usually normal MCHC (can be reduced in IDA)

Question 25

How is the diagnosis of ß-thalassaemia trait made?

Answer 25

1. microcytosis + increase of HbA2

Question 26

What are the different forms of Beta-thalassaemia major that can be present?

Answer 26

ß-globin mutations can lead to absence of ß-chain formation ß0 or severely reduced formation (ß+)

Question 27

When does beta-thalassaemia major usually clinically present?

Answer 27

In first 3-6 months of life (due to reduction of HbF)

But shoulle be picked up by Heel prick test

Question 28

What are the clinical effects of poorly treated thalasseamia major?

Answer 28

1. Anaemia –> heart failure, growth retardation
2. Increased Erythropoietic drive –> bone expansion, hepatic-splenomegaly
3. Iron overload –> heart failure, gonadal failure

Question 29

What is the prognosis and clinical management of beta-thalassaemia?

Answer 29

Without treatment life expectancy is only a few years

1. Regular Blood transfusions
2. Iron chelation
3. Curative: BM transplant in young children not yet iron overloaded

Question 30

Summarise the different forms of alpha-thalassaemia and their prognosis

Answer 30

Overall four alpha genes
1. Deletion of 1-2:no significance for individual, might be significant for pregnancy if both partners

2. 3 alpha chains deleted: haemoglobin h disease, –> microcytosis + hepato-splenomegaly. viable, not clinically severe enough to justify termination
3. 4 alpha-chains deleted: not viable and death in utero or shortly after birth (Barts hydrops fetalis)