10. Paediatric haematology Flashcards
(104 cards)
1
Q
What can lead to one twin becoming anaemic and the other becoming polycythaemia?
A
Shared placental circulation
2
Q
What are causes of polycythaemia in foetuses?
A
Twin-to-twin transfusion, intrauterine hypoxia, placental insufficiency
3
Q
What are causes of anaemia in foetuses?
A
Twin-to-twin transfusion; foetal-to-maternal transfusion; parvovirus infection (virus not cleared by immature immune system); haemorrhage from cord or placenta
4
Q
What are other causes of damage to the foetus (give 5 causes)?
A
- Irradiation,
- damage by something crossing the placenta (e.g. drugs, chemicals, antibodies);
- anticoagulants (can cause haemorrhage or foetal deformity (e.g. vitamin K if given in the first trimester));
- antibodies can destroy red cells, white cells or platelets;
- substances in breast milk (e.g. a G6PD deficient baby may suffer from haemolysis if their mother eats fava beans).
5
Q
When does the first mutation that subsequently leads to childhood leukaemia develop?
A
In utero
6
Q
Can pre-leukaemic cells spread from one twin to the other?
A
Yes, pre-leukaemic cells carrying this mutation can even spread from one twin to the other
7
Q
Leukaemia can develop in utero and manifest in the neonate. What condition is congenital leukaemia particularly common in?
A
Down syndrome
8
Q
What is congenital leukaemia sometimes called?
A
Transient abnormal myelopoiesis
9
Q
How is congenital leukaemia/ transient abnormal myelopoiesis (TAM) different from leukaemia in older children?
A
Disease tends to remit spontaneously within the first two months. However it tends to relapse 1-2 years later in about 25% of infants.
10
Q
What is the capacity of spontaneous remission of congenital leukaemia similar to?
A
Neuroblastoma
11
Q
Congenital leukaemia is myeloid with major involvement of which lineage?
A
Megakaryocyte
12
Q
What two terms are used to describe defects in the synthesis of globin chains?
A
Haemoglobinopathies and thalassemias
13
Q
What is a thalassemia?
A
A condition resulting from a reduced rate of synthesis of one or more of the globin chains as a result of a genetic defect
14
Q
What is a haemoglobinopathy?
A
Refers to a structurally abnormal haemoglobin (NOTE: some consider thalassemia to be a form of haemoglobinopathy)
15
Q
What are the different times in life that defects in alpha globin chain and beta globin chain occur?
A
Defects in alpha globin chain and beta globin chains occur at different times in life because alpha globin synthesis begins early in foetal life whereas beta globin synthesis begins late in gestation
16
Q
What genes are the globin chains controlled by?
A
The globin chains are controlled by globin genes on chromosome 11 and chromosome 16
17
Q
What genes does chromosome 11 have?
A
Chromosome 11 has the beta cluster. It has: beta gene, delta gene, gamma gene, and the locus control region is required for the synthesis of all chains. Epsilon is an embryonic globin gene
18
Q
What genes does chromosome 16 have?
A
2x alpha genes, zeta gene - expressed in the embryo
19
Q
What are normal forms of haemoglobin?
A
A, A2 and F
20
Q
What globin chains are associated with haemoglobin A?
A
alpha2beta2
21
Q
What period is haemoglobin A mainly present?
A
Late, foetus, infant, child and adult
22
Q
What globin chains are associated with haemoglobin A2?
A
alpha2delta2
23
Q
What period is haemoglobin A mainly present?
A
Infant, child and adult
24
Q
What globin chains are associated with haemoglobin F?
A
alpha2gamma2
25
What period is haemoglobin F mainly present?
Foetus and infant
26
What percentage of total adult haemoglobin should HbA2 be?
<3.5%
27
Describe how haemoglobin changes throughout foetal life (from conception until 9 months of age)?
There are some specific foetal haemoglobins present in the first 16 weeks from conception (Haemoglobins Gower 1, Gower 2, Portland 1). Then HbF predominates throughout most of foetal life. After around 32 weeks you get a rapid increase in HbA production. At birth, about 1/3 of haemoglobin is HbA, but this rapidly increases after birth. Low levels of haemoglobin A2 are seen after week 30 (?) from conception, and remain at low levels after birth.
28
What is the difference between sickle cell anaemia (HbSS) and sickle cell disease?
Sickle cell anaemia refers to homozygosity of the HbS gene. Sickle cell disease encompasses homozygous AND heterozygous states associated with sickling.
29
SCD includes compound heterozygous states such as?
HbSC and HbS/beta thalassemia
30
What is the pathophysiology of SCD?
- HYPOXIA leads to polymerisation of haemoglobin S leading to crescent shaped red blood cells and blocked blood vessels.
- This tends to occur in post-capillary venules.
- When passing through these venules, red cells tend to elongate.
- If the circulation slows, the cells will begin sickling and becoming adherent to the endothelium which causes obstruction.
- Retrograde capillary obstruction results in arterial obstruction.
- At the beginning of the hypoxic stimulus, the cells may start to become distorted, however, this is reversible once the hypoxic state resolves.
- A lot of the cells that become very sickled will be irreversible.
31
What are Howell Jolly bodies a feature of?
Howell Jolly bodies are a feature of hyposplenism (e.g. due to splenic infarction)
32
How does sickle cell trait (HbAS) manifest?
Totally asymptomatic
33
What is the severity of HbSC in comparison to HbSS?
HbSC causes a sickling disorder that is slightly milder than HbSS
34
What does the severity of HbS/beta thalassemia depend on?
HbS/beta thalassemia severity depends on whether it is a beta-0 gene (no beta globin production) or beta+ gene (a little bit of beta globin production)
35
When does sickle cell anaemia start to manifest?
Sickle cell anaemia become manifest as gamma chain production and HbF synthesis DECREASE and HbS production INCREASE. This occurs around 6 months of age.
36
In the UK when is sickle cell anaemia usually diagnosed and how?
In the UK, sickle cell anaemia is usually diagnosed AT BIRTH (Guthrie test)
37
Universal neonatal screening must be coordinated with universal antenatal screening. The antenatal screening is based on risk, such as? Why is this important to make the diagnosis at birth?
The antenatal screening is based on risk (e.g. ethnicity, prevalent areas). Making a diagnosis as a neonate allows prevention and anticipation of some of the complications.
38
Why does sickle cell anaemia in a child differs from the same disease in the adult, regarding the bone marrow?
This is because the distribution of red bone marrow differs. When born, all bone marrow is red, and eventually gets converted to yellow bone by age 7. Red bone marrow is vascular, metabolically active and requires an oxygen supply so it is susceptible to infarction. Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia.
39
What does red and yellow bone marrow contain?
Red bone marrow is the type of bone marrow that contains haemopoietic precursors with developing red cells and white cells. Yellow marrow is largely fat.
40
Where does bone pain due to infarction happen in adults and infants/children?
In ADULTS, this will only happen in the central skeleton. In INFANTS and CHILDREN, this can happen all the way down to the fingertips (hand/foot syndrome).
41
Why does sickle cell anaemia in a child differs from the same disease in the adult, regarding the spleen? And what adverse events in children can this lead to?
Another reason for the difference in clinical manifestation between infant and adult is that the infant still has a functioning spleen. This means that the child can undergo splenic sequestration which is the acute pooling of a large percentage of circulating red cells in the spleen. This can also lead to SEVERE ANAEMIA, SHOCK and DEATH.
42
What should parents of children with sickle cell anaemia be taught to do?
Parents should be taught how to palpate the spleen and to seek medical attention if the child is acutely unwell with an enlarged spleen.
43
Why does splenic sequestration leading to adverse events tend not to occur in older children and adults?
Because recurrent infarction has left the spleen small and fibrotic
44
How can we treat splenic sequestration?
The patient should receive a blood transfusion
45
What does spleen do?
The spleen is an important part of the immune system - it filters out bacteria and parasites
46
As the risk of splenic sequestration wanes when the spleen becomes small and fibrotic, what happens to the risk of hyposplenism?
The risk of hyposplenism increases
47
When does hand-foot syndrome tend to occur?
Hand-foot syndrome tends to occur in the first 2 years of life
48
What is acute chest syndrome?
Acute chest syndrome is caused by infarction in the ribs and lungs
49
When does acute chest syndrome tend to occur?
Throughout childhood (and beyond?). 34% at 3 years and 15% at 9 years
50
What is one of the MOST COMMON causes of stroke in childhood
Sickle cell anaemia
51
What is the cumulative incidence of stroke in the first decade?
4-8%
52
What is the risk of painful crises in the first decade?
About 40% per year
53
What are sickle cell anaemia patients susceptible to at younger ages irrespective of hyposplenism?
Bacteraemia
54
When does splenomegaly tend to occur in the first decade of life?
Highest risk at 1 years old, lowers until 5 years old
55
When does acute splenic sequestration tend to occur?
Between 1-3 years old
56
Which infections are children with SCA particularly vulnerable to?
Pneumococcus and parvovirus because they would not have encountered them before
57
What can cause aplastic anaemia in sickle cell anaemia?
Parvovirus
58
Pneumococcal infection is often FATAL in babies with sickle cell anaemia. How can this be prevented?
This can be prevented with a combination of vaccination and penicillin
59
Children with sickle cell anaemia have increase folic acid demands due to:
Hyperplastic erythropoiesis, growth spurts, red cell lifespan is shorted so anaemia can rapidly worsen
60
What are the principles of treatment of SCA?
Establish a diagnosis (using a normal blood test in addition to the Guthrie test), educate parents, vaccinate, prescribe folic acid and penicillin.
61
When does beta thalassemia manifest and why?
This will manifest after the first 6 months of life because of the decline of synthesis of HbF and the increased production of HbA.
62
How is beta thalassemia first suspected?
It can be suspected at birth through the Guthrie spot test. The blood will have NO haemoglobin A.
63
What is the difference in severity between beta thalassemia trait and homozygosity?
Beta thalassemia trait is harmless but genetically important. Beta thalassemia homozygosity causes a SEVERE anaemia. This can be FATAL in the first few years of life without blood transfusions
64
What are the intermediate forms of beta thalassemia called?
Beta thalassemia intermedia
65
What are clinical features of poorly treated thalassemia major?
Anaemia --> heart failure, growth retardation. Erythropoietic drive --> bone expansion, hepatomegaly, splenomegaly. Iron overload --> heart failure, gonadal failure.
66
What is an important aspect of thalassemia major treatment?
Iron chelation is an important aspect of treatment
67
What are the principles of treatment of beta thalassemia major?
Accurate diagnosis and family counselling; blood transfusion; once iron overload starts to occur, chelation therapy is necessary (desferrioxamine, deferiprone); consider the child as an individual and as part of the family.
68
Is haemolytic anaemia inherited or acquired?
Can be inherited or acquired
69
When do severe forms of inherited haemolytic anaemia tend to manifest?
In childhood
70
Children can only get a few types of acquired haemolytic anaemia, true or false?
False. Children can also get most types of acquired haemolytic anaemia.
71
Is congenital haemolytic anaemia mostly acquired or inherited?
Mostly inherited
72
What can transplacental passage of maternal antibodies cause?
Haemolytic disease of the newborn
73
Which antibodies is HDN usually due to?
ABO and RhD ABx
74
What are inherited haemolytic anaemias due to defects in?
Red cell membrane (hereditary spherocytosis, hereditary eliptocytosis), haemoglobin molecule (SCA), glycolytic pathway enzymes (pyruvate kinase deficiency) and pentose shunt (G6PD deficiency)
75
Where is the defect in hereditary spherocytosis, causing inherited haemolytic anaemia?
Red cell membrane
76
Where is the defect in hereditary eliptocytosis, causing inherited haemolytic anaemia?
Red cell membrane
77
Where is the defect in sickle cell anaemia, causing inherited haemolytic anaemia?
Haemoglobin molecule
78
Where is the defect in pyruvate deficiency, causing inherited haemolytic anaemia?
Glycolytic pathway enzymes (which provide energy to the cell)
79
Where is the defect in G6PD deficiency, causing inherited haemolytic anaemia?
Pentose shunt (which protect the cell from oxidant damage)
80
What are the main principles in diagnosing haemolytic anaemia?
Consider if there is: anaemia; increased red cell turnover (e.g. jaundice, splenomegaly, increased conjugated bilirubin); increased red cell production (e.g. increased reticulocyte count, bone expansion); abnormal red cells
81
What results in anaemia in SCA?
The nature of the anaemia in sickle cell anaemia is NOT totally due to haemolysis alone. HbS is a low affinity haemoglobin meaning that it released oxygen readily to tissues so the EPO-drive is lower which results in anaemia.
82
Example: A 7 y/o Afro-Caribbean boy had abdominal pain and urinary tract symptoms and was given an anti-emetic by his GP. Three days later he was noted to have yellow eyes and was brought to the hospital. WBC 10.9 x 10^9/L, Hb 58g/L, MCV 100 fL, platelet count 275 x 10^9/L. This condition is resulting from oxidant damage in a child with G6PD deficiency. What are the triggers of haemolysis in G6PD deficiency?
Triggers of haemolysis in G6PD deficiency: infections; drugs; naphthalene; fava beans (broad beans)
83
What is the inheritance pattern of G6PD deficiency?
G6PD deficiency is X-linked meaning that most people who suffer from it are males
84
What are the two main types of acquired haemolytic anaemias?
Autoimmune haemolytic anaemia and haemolytic uraemic syndrome
85
What is autoimmune haemolytic anaemia characterised by?
Spherocytosis and positive DAT (Coombs' test)
86
What is haemolytic uraemic syndrome characterised by?
Haemolysis, uraemia
87
What is microangiopathic haemolytic anaemia (MAHA)?
When the red cells are damaged in capillaries forming small angular fragments and microspherocytes
88
Inherited defects of coagulation - what are the least rare defects?
Haemophilia A, Haemophilia B, Von Willebrand disease
89
How does haemophilia A and B present?
Bleeding following circumcision, haemarthroses when starting to walk, bruises, post-traumatic bleeding
90
What are the differential diagnoses for Haemophilia A and B?
Inherited thrombocytopaenia or platelet functional defect; acquired defects of coagulation (e.g. ITP, acute leukaemia); non-accidental injury; Henoch-Schonlein purpura
91
What are the key aspects of the history in a child with a suspected inherited defect of coagulation?
History of the child, family history, coagulation screen, platelet count, assays of specific coagulation factors.
92
What specific details of the child's history do you want to know to help diagnose an inherited defect of coagulation?
Was there umbilical cord bleeding or bleeding when the Guthrie test was performed? Was there haematoma formation after vitamin K injection or vaccinations? Was there bleeding after circumcision?
93
What are the principles of treatment/management of inherited defects of coagulation?
Accurate diagnosis; counselling the family; treatment of bleeding episodes; use of prophylactic coagulation factors; consideration of the child as an individual and as a family member (home treatment, self-treatment, schooling)
94
What is the presentation of von Willebrand disease?
Mucosal bleeding; bruises; post-traumatic bleeding
95
What are differential diagnoses for vWD?
Haemophilia A. NOTE: this is because factor 8 is low in both conditions
96
How can we diagnose vWD?
Family history (mainly autosomal dominant); coagulation screen; Factor 8 assay; bleeding time; platelet aggregation studies
97
What is the treatment of von Willebrand disease?
Lower purity factor 8 concentrates
98
Case: A 1 y/o boy presents with joint bleeding, Hb, WBC, and platelet count are normal, apTT is prolonged, PT is normal, bleeding time normal - most likely diagnosis?
This is most likely haemophilia A because it is 4 x more common than haemophilia B
99
What is the presentation of autoimmune thrombocytopaenic purpura?
Petechiae, bruises, blood blisters in the mouth
100
What are differential diagnoses of autoimmune thrombocytopaenic purpura?
HSP; non-accidental injury; coagulation factor defect; inherited thrombocytopaenia; acute leukaemia
101
How can we diagnose autoimmune thrombocytopenic purpura?
History; blood count and film; bone marrow aspirate (only if good reason)
102
What is the treatment for autoimmune thrombocytopenic purpura?
Observation (most common); corticosteroids; high dose IVIG; IV anti-RhD (if RhD positive)
103
Which acute leukaemia is more common and what ages do they occur at?
ALL is the MOST COMMON. Most childhood leukemias are acute lymphocytic leukemia (ALL). AML occurs at all ages. < 1 year old - AML is more common than ALL.
104
What is the management of hyposplenism?
Appropriate vaccinations, prophylactic penicillin, advice to parents regarding other risks, malaria, and dog bites
