Haem: Paediatric haematology Flashcards
1
Q
Which feature of children predisposes them to nutrient deficiency?
A
Rapid growth
2
Q
How is the immune response to infection different in children compared to adults?
A
Children are more likely to mount a lymphocytosis as they frequently encounter new pathogens
3
Q
What are the main differences between the blood count of neonate and an adult?
A
- Higher WCC (neutrophils, lymphocytes)
- Higher Hb
- Higher MCV
4
Q
How are the enzyme levels in the red blood cells of neonates different to adults?
A
They have 50% of the concentration of G6PD of adults
5
Q
List some causes of polycythaemia in a foetus.
A
- Twin-to-Twin transfusion syndrome
- Intrauterine hypoxia
- Placental insufficiency
6
Q
List some causes of anaemia in a foetus.
A
- Twin-to-Twin transfusion syndrome
- Foetal-to-Maternal transfusion
- Parvovirus infection
- Bleeding from cord or placenta
7
Q
List some causes of damage to the red blood cells of a foetus.
A
- Irradiation
- Damage by something crossing the placenta (e.g. drugs, antibodies)
- Anticoagulants
- Substances in breast milk (e.g. fava beans in a baby with G6PD deficiency
8
Q
When does the first mutation that leads to childhood leukaemia often occur?
A
In utero
9
Q
Which condition is assocaited with congenital leukaemia?
A
Down syndrome
10
Q
What is another term to describe congenital leukaemia?
A
Transient abnormal myelopoiesis (TAM)
11
Q
Describe the usual course of congenital leukaemia.
A
- Remits spontaneously within the first 2 months of life
- However, 25% of infants will relapse after 1-2 years
- NOTE: the leukaemia is myeloid with major involvement of the megakaryocyte lineage
12
Q
Define thalassaemia.
A
A group of conditions resulting from a reduced rate of synthesis of one or more globin chains as a result of a genetic defect.
13
Q
Define haemoglobinopathy.
A
Refers to a structurally abnormal haemoglobin.
NOTE: thalassemias are sometimes considered a form of haemoglobinopathy
14
Q
On which chromosomes are the different globin genes expressed?
A
Chromosone 11
- Beta
- Delta
- Gamma
- Epsilon
Chromosone 16
- 2x alpha
- Zeta
15
Q
Which globin chains are found in the following types of haemoglobin:
- HbA
- HbA2
- HbF
A
- HbA = 2 alpha, 2 beta
- HbA2 = 2 alpha, 2 delta
- HbF = 2 alpha, 2 gamma
16
Q
What is the normal HbA2 level in a healthy adult?
A
< 3.5%
17
Q
Describe how the haemoglobin levels in utero change.
A
- Some specific foetal haemoglobins (epsilon, zeta etc) are present in the first 16 weeks
- HbF predominates throughout most of foetal life
- After around 32 weeks, there is a rapid increase in HbA production
- At birth, around 1/3 haemoglobin is HbA but this rapidly increases after birth
18
Q
What is the difference between sickle cell anaemia and sickle cell disease?
A
- Sickle cell anaemia - homozygosity for HbS gene
- Sickle cell disease - encompasses homozygous and heterozygous states associated with sickling (including HbSC and HbS/beta thalassemia)
19
Q
Outline the pathophysiology of sickle cell anaemia.
A
- Hypoxia leads to polymerisation of HbS leading to crescent-shaped red blood cells and blocker blood vessels
- This tends to occur in post-capillary venules
- When passing through these venules, red cells tend to elongate
- If the circulation slows down, cells will begin sickling and stickling to the endothelium causing obstruction
- Retrograde capillary obstruction results in arterial obstruction
- Early on, the sickling may be reversible by correcting the hypoxia
- However, the cells can become irreversibly sickled
20
Q
What feature of hyposplenism might you seeon a blood film of a patient with sickle cell anaemia?
A
Howell Jolly bodies
21
Q
Describe the severity of the following types of sickle cell disease:
- Sickle cell trait
- Sickle cell anaemia
- HbSC
- HbS/beta thalassemia
A
-
Sickle cell trait
- Usually asymptomatic
-
Sickle cell anaemia
- Manifests when HbF decreases and HbS increases (at 6 months age)
- Severe symptoms
-
HbSC
- Slightly milder than sickle cell anaemia
-
HbS/beta thalassemia
- Severity depends on whether it is beta-0 gene (no globin production) or beta+ gene (some globin production)
22
Q
When is sickle cell anaemia usually diagnosed in the UK?
A
At birth following the Guthrie test
23
Q
Why does sickle cell anaemia in a child differ from sickle cell anaemia in an adult?
A
- Mainly because the distribution of red bone marrow (contains haematopoietic precursors) differs
- Red bone marrow is vascular, metabolically active and susceptible to infarction
- Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia
24
Q
How is the pattern of bone pain due to infarction different in adults with sickle cell anaemia compared to children?
A
- Adults - only happens in central skeleton
- Infants/Children - can happen anywhere (including hands and feet causing hand-foot syndrome)
25
How is splenic function different in children with sickle cell anaemia compared to adults and what risks does this pose?
* Children still have functioning spleens meaning that a child is much more likely to undergo splenic sequestration
* This can lead to severe anaemia, shock and death
* Teenagers and adults don't tend to experience splenic sequestration because recurrent infarction has left their spleen small and fibrotic
* However, as the risk of splenic sequestration declines with time, the risks of hyposplenism increase
26
Define splenic sequestration.
Acute pooling of a large percentage of circulating red cells in the spleen
27
How is splenic sequestration managed?
* Parents should be taught how to palpate the spleen and to seek help when the child is acutely unwell with a large spleen
* Blood transfusion
28
Which age groups tends to be affected by hand-foot syndrome?
\< 2 years
29
Which complication of sickle cell anaemia occur in younger children (2-10 years old)?
* Acute chest syndrome (caused by infarction of the ribs and lungs)
* Painful crises
* Stroke (SCD is the most common cause of stroke in children)
30
How does the susceptibility to bacteraemia change throughout the life of a patient with sickle cell anaemia?
* Highest at younger ages irrespective of hyposplenism
* Decreases with age
31
Which infectious agents are children with sickle cell anaemia particularly vulnerable to?
* Pneumococcus
* Parvovirus B19 (causes aplastic anaemia)
32
How can pneumococcal infection be prevented in a patient with sickle cell anaemia?
* Vaccination
* Prophylactic antibiotics
33
Why do children with sickle cell anaemia have increased folate demands?
* Hyperplastic erythropoiesis
* Growth spurts
* Reduced red cell lifespan
34
What are the principles of managing sickle cell anaemia?
* Educate parents
* Vaccinate
* Prescribe folic acid and penicillin
35
Describe the difference in severity of beta thalassaemia trait and beta thalassaemia major.
* Trait - harmless but genetically important (can impact children)
* Major - severe anaemia that is tranfusion-dependent
NOTE: there is an immediate form of the disease called beta-thalassaemia intermedia
36
List some clinical features of poorly controlled beta thalassaemia major.
* Anaemia → heart failure, growth retardation
* Erythropoietic drive → bone expansion, hepatomegaly, splenomegaly
* Iron overload → heart failure, gonadal failure
37
What are the principles of treatment of beta thalassaemia major?
* Accurate diagnosis and family counselling
* Blood transfusion
* Iron chleation
38
List some types of inherited haemolytic anaemia.
* **Red cell membrane** - hereditary spherocytosis, hereditary eliptocytosis
* **Haemoglobin molecule** - sickle cell anaemia
* **Glycolytic pathway -** pyruvate kinase deficiency
* **Pentose shunt** - G6PD deficiency
39
What should you look for when investigating a patient with suspected haemolytic anaemia?
* Is there anaemia?
* Is there evidence of increased red cell turnover? (e.g. jaundice, splenomegaly)
* Is there evidence of increased red cell production? (e.g. increased reticulocyte count, bone expansion)
* Are there abnormal cells?
40
Aside from the haemolysis, what else contributes to anaemia in sickle cell anaemia?
* HbS has a low affinity for oxygen meaning that is releases oxygen readily to tissues
* This reduces EPO-drive
41
List some triggers for haemolysis in G6PD deficiency.
* Infections
* Drugs
* Naphthalene
* Fava beans
42
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
43
What are the two main types of acquired haemolytic anaemia?
* Autoimmune haemolytic anaemia
* Haemolytic uraemic syndrome
44
What are the characteristic features of autoimmune haemolytic anaemia?
* Spherocytes
* Positive DAT
45
What is MAHA?
* Breaking up of red cells into fragments due to shearing as it passes through fibrin strands within capillaries
46
What are the most common inherited defects of coagulation?
* Haemophilia A
* Haemophilia B
* Von Willebrand disease
47
Describe the typical presentation of haemophilia A and B in an infant.
* Bleeding following circumcision
* Haemarthrosis when starting to walk
* Bruises
* Post-traumatic bleeding
48
List some differential diagnoses for haemophilia.
* Inherited thrombocytopaenia/platelet defect
* Acquired defects of coagultion (e.g. ITP, acute leukaemia)
* Non-accidental injury
* Henoch-Schonlein purpura
49
What are some key aspects of investigating a child with a suspected defect of coagulation?
* Family history
* Coagulation screen
* Platelet count
* Assays for specific coagulation factors
50
List some specific details of an infant's early history that could be suggestive of a disorder of coagulation.
* Bleeding from the umbilical cord
* Bleeding after the Guthrie test
* Haematoma formation after vitamin K injection/vaccines
* Bleeding after circumcision
51
What are the principles of treatment of inherited disorders of coagulation?
* Counselling the family
* Treatment of bleeding episodes
* Use of prophylactic coagulation factors
52
Describe the typical presentation of von Willebrand disease.
* Mucosal bleeding
* Bruises
* Post-traumatic bleeding
53
Why do von Willebrand disease and haemophilia A present similarly?
They are both characterised by low level of factor 8
54
How is von Willebrand disease diagnosed?
* Family history (mainly autosomal dominant(
* Coagulation screen
* Factor 8 assay
* Bleeding time
* Platelet aggregation studies
55
How is von Willebrand disease treated?
Lower purity factor 8 concentrates
56
Describe the relative prevalence of haemophilia A and B.
Haemophilia A is 4x more common than haemophilia B
57
Describe the typical presentation of ITP.
* Petechiae
* Bruises
* Blood blisters in the mouth
58
List some differential diagnoses for ITP.
* Henoch-Scholein Purpura
* Non-accidental injury
* Coagulation factor defect
* Inherited thrombocytopaenia
* Acute leukaemia
59
List some treatment approcahes for ITP.
* Observation (most common)
* Corticosteroids
* High dose IVIG
* IV anti-RhD (if RhD positive)
60
Which type of leukaemia is most common in children?
ALL
NOTE: \< 1 years old AML is more common than ALL
61
How is hyposplenism managed?
* Vaccination
* Prophylactic penicillin
* Advice about other risks (e.g. malaria, dog bites)
