Haem - Paediatric haematology Flashcards
What predisposes children to nutrient deficiency (and which)
Rapid growth and poor nutrient intake
Iron deficiency, folic acid deficiency
What complications could paediatric haematological disorders lead to
Growth retardation can occur with illness or due to its treatment (i.e. old ALL spinal irradiation treatment)
Pubertal failure / development of 2nd sexual characteristics from illness or treatment (e.g. b-thalassemia major treatment → iron overload )
What are the differences in neonatal blood value ranges compared to adults
Higher:
WCC
Neutrophils
Lymphocytes
Hb
MCV
+ higher HbF %
What are the causes of polycythaemia in the foetus
Twin-to-twin transfusion
Intrauterine hypoxia (foetus responds by increased EPO)
Placental insufficiency
What are the causes of anaemia in the foetus
Twin-to-twin or Foetal-to-maternal (rare) transfusion
Parvovirus infection B19 (virus not cleared by immature immune system)
Haemorrhage from cord or placenta
How are foetal RBC enzymes different to adults’ enzymes
~50% the G6PD concentration of an adult
What are the causes of haematological damage in the foetus
Irradiation
Damage by something crossing the placenta (e.g. drugs, chemicals, antibodies)
Anticoagulants (→ 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. G6PDD-baby may suffer from haemolysis if mother eats fava beans)
Describe the association between Down’s syndrome and leukaemia
Down’s syndrome is associated with congenital leukaemia (transient abnormal myelopoiesis)
○ This is different from leukaemia in older children (TAM is a myeloid leukaemia)
○ This disease tends to remit spontaneously within the first 2 months of life
○ However, it tends to relapse 1-2 years later in about 25% of infants
○ The capacity for spontaneous remission is similar to neuroblastoma
What are haemoglobinopathies
structurally abnormal Hb
Define thalassaemia
Group of genetic disorders characterised by a defect in and reduced globin chain synthesis
What are the differences in the timing globin chain synthesis
alpha globin synthesis begins early in foetal life
beta globin synthesis begins late in gestation
Describe the beta cluster in globin synthesis
Chromosome 11: beta, delta, gamma, epsilon (embyronic)
Deletion of the locus control region B (LCRB) → reduced globin expression
Describe the alpha cluster in globin synthesis
Chromosome 16: alpha 1, alpha 2, zeta (embryonic)
Deletion of locus control region A (LCRA) → reduced globin expression
Describe haemoglobin A and when it is present
𝛼2β2
Late foetus, infant, child, adult
Describe haemoglobin A2 and when it is present
𝛼2δ2
Infant, child, adult (<3.5%)
Describe haemoglobin F and when is it present
𝛼2γ2
Foetus and infant
Describe haemoglobin in utero
Specific foetal haemoglobins are present in the first 16 weeks → HbF predominates
After around 32 weeks you get a rapid increase in HbA production
At birth, about 1/3rd of haemoglobin is HbA, but this rapidly increases after birth
HbA2 production is much slower and starts from birth
What is the pathophysiology of sickle cell disease
Usually RBCs elongate to pass through the capillary beds to post-capillary venules
(1) Hypoxia → polymerisation of haemoglobin S → crescent shaped RBCs and blocked blood vessels (usually reversible when hypoxia is resolved)
(2) If circulation slows, the cells sickle and become rigid and adherent to the endothelium which causes obstruction
(3) Retrograde capillary obstruction → arterial obstruction
What are the types of sickle cell disease
ββS / AS: Sickle cell trait (not sickle cell disease)
βSβS / SS: Sickle cell anaemia
βC / SC: Sickle cell / haemoglobin C disease (Compound - Sickling slightly milder than HbSS)
βSβThal: Sickle cell / beta thalassaemia (Compound)
What does severity of compound sickle cell (βSβThal) depend on
whether it is a:
Beta-0 gene (no beta globin production)
Beta+ gene (a little bit of beta globin production)
At what time does sickle cell anaemia and beta thalassaemia start to clinically manifest and why
3-6 months of life
Gamma chain production and HbF synthesis DECREASE
HbS , HbA production INCREASE
What are the symptoms of sickle cell anaemia in children
Hand-foot syndrome (swelling) (red bone marrow extends into the digits)
Splenomegaly
Acute splenic sequestration
Acute chest syndrome
Painful crises (40%)
Stroke(4-8%)
Hyposplenism
Bacteraemia
What are the types of bone marrow
Yellow BM is largely fat
Red BM produces haematopoietic precursors with developing RBCs and white cell and is vascular, metabolically active and requires an oxygen supply, so it is susceptible to infarction
What is the difference between adult and child splenic complications of sickle cell anaemia
Adult / older-child spleen – spleen is small and fibrotic from recurrent infarction
Suffer from more chance of sequalae of hyposplenism (i.e. pneumococcal infection)
Child spleen – still has a functioning spleen
Children can undergo splenic sequestration which is the acute pooling of a large percentage of circulating red cells in the spleen → SEVERE ANAEMIA, SHOCK and DEATH
What infections are children with sickle cell more susceptible to
Pneumococcus
Parvovirus B19 → aplastic naemia
Why do children with sickle cell anaemia have increased folic acid demands
Hyperplastic erythropoiesis
Growth spurts
Red cell lifespan is shorted so anaemia can rapidly worsen
What are the principles of sickle cell anaemia treatment
Establish a diagnosis (using a normal blood test in addition to the Guthrie test)
Educate parents + Parents should be taught how to palpate the spleen and to seek medical attention if needed
Vaccinate (pneumococcal)
Folic acid supplements
Daily penicillin prophylaxis
Blood transfusion required
What are the types of beta thalassaemia
BthalB: beta thal trait
BthalBthal: beta thal major
BthalBthal: beta thal intermedia (some HbA due to + forms)
What are the clinical features of poorly treated thalassaemia major
Anaemia → heart failure, growth retardation
Erythropoietic drive in the kidney (due to anaemia) → bone expansion, hepatomegaly, splenomegaly
Iron overload (regular blood transfusions) → heart failure, gonadal failure
What are the principles of beta thalassaemia major treatment
Accurate diagnosis and family counselling
Regular Blood transfusion
± iron chelation due to risk of overload → desferrioxamine, deferiprone
What are the causes of congenital haemolytic anaemia that are not inherited
Transplacental passage of maternal antibodies can cause haemolytic disease of the newborn (usually due to ABO and RhD antibodies)
What are the causes of inherited haemolytic anaemia
Red cell membrane: hereditary spherocytosis/eliptocytosis
Haemoglobin molecule: sickle cell anaemia
Glycolytic pathway enzymes: pyruvate kinase deficiency (provide energy to cell)
Pentose-phosphate shunt: G6PD deficiency (protect cell from oxidant damage)
What drives the anaemia in sickle cell anaemia
Haemolysis of sickled cells
HbS is low affinity → readily releases O2 to tissues → EPO drive is lower → reduced RBC production → Anaemia
What are the clinical signs of increased red cell turnover
Jaundice
Splenomegaly
Increased unconjugated bilirubin
What are the clinical signs of increased red cell production
Increased reticulocyte count
Bone expansion
What are the signs of the following on blood smear: G6PD, hereditary spherocytosis, MAHA
G6PD - Bite cells, Heinz bodies, irregularly contracted cells
Hereditary spherocytosis - spherocytes
MAHA - schistocytes
What are the triggers of haemolysis in G6PD deficiency
Infections (? UTI)
Drugs (? anti-emetic)
Naphthalene (moth balls)
Fava beans (broad beans)
What are the types of immune haemolytic anaemias and what are their features
Autoimmune haemolytic anaemia
- Spherocytosis
- Positive DAT (Coombs’ test)
Haemolytic uraemic syndrome:
- Haemolysis
- Uraemia
What is MAHA
Microangiopathic haemolytic anaemia (MAHA) is when the red cells are damaged in capillaries forming small angular fragments and micro-spherocytes (schistocytes)
Give examples of inherited disorders of coagulation
Haemophilia A (F8)
Haemophilia B (F9)
Von Willebrand disease (platelets, F8)
What are the clinical features of inherited disorders of coagulation
Bleeding following circumcision
Haemarthroses when starting to walk
Bruises
Post-traumatic bleeding
What are some clues of an inherited defect of coagulation in children
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?
What is the difference in investigation results between haemophilia and VWD
VWD; bleeding time prolonged, FVIII low
Haemophilia (A): FVIII low, bleeding time normal
What are the differentials for bruising and easy bleeding
HSP
Non-accidental injury
Coagulation factor defect
Inherited thrombocytopaenia
Acute leukaemia
ITP
What is the presentation of ITP
Petechiae
Bruises
Blood blisters in the mouth
What is the treatment for ITP
Observation (most common)
Corticosteroids
High dose IVIG
Anti-D (in RhD +ve with spleen)
What is the most common leukaemia in children <1 years old and >1 years old
ALL is the MOST COMMON (200 cases a year)
Less than 1-year-old – AML is more common than ALL
What is the management for hyposplenism
Appropriate vaccinations
Prophylactic penicillin
Advice to parents regarding other risks
Malaria
Dog bites
