Haem: Paediatric haematology Flashcards
Which feature of children predisposes them to nutrient deficiency?
Rapid growth
deficinecy in Fe, B12 are common
How is the immune response to infection different in children compared to adults?
Children are more likely to mount a lymphocytosis as they frequently encounter new pathogens
What are the main differences between the blood count of neonate and an adult?
- Higher WCC (neutrophils, lymphocytes)
- Higher Hb - more HbF
- Higher MCV
Why does beta thalassemia major not manifest at birth
will only present 3-6 months later when fetal haemoglboin decreases and production of HbA is not switched on
similarly sickle cell would not manifest until 3-6months later when HbF decreases and HbS increases but it is tested for at birth
alpha thalassemia does as it alpha globin needed for HbF
How are the enzyme levels in the red blood cells of neonates different to adults?
G6PD conc in neoates is 50% higher than in adults
List some causes of polycythaemia in a foetus.
- Twin-to-Twin transfusion syndrome
- Intrauterine hypoxia
- Placental insufficiency
List some causes of anaemia in a foetus.
- Twin-to-Twin transfusion syndrome - haemorrhage from one twin to another, one has anaemia, the other has polycthaemia
- Foetal-to-Maternal transfusion - fetus bleeds into maternal circulation
- Maternal Parvovirus infection
- Bleeding from cord or placenta
List some causes of damage to the red blood cells of a foetus.
- Irradiation
- Damage by something crossing the placenta (e.g. drugs, antibodies)
- Anticoagulants - warfarin
- Substances in breast milk (e.g. fava beans in a baby with G6PD deficiency
When does the first mutation that leads to childhood leukaemia often occur?
In utero
Which condition is assocaited with congenital leukaemia?
Down syndrome
What is another term to describe congenital leukaemia?
Transient abnormal myelopoiesis (TAM)
Describe the usual course of congenital leukaemia.
- 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
Define thalassaemia.
A group of conditions resulting from a reduced rate of synthesis of one or more globin chains as a result of a genetic defect.
Define haemoglobinopathy.
Refers to a structurally abnormal haemoglobin.
NOTE: thalassemias are sometimes considered a form of haemoglobinopathy
On which chromosomes are the different globin genes expressed?
Chromosone 11
- Beta
- Delta
- Gamma
- Epsilon
Chromosone 16
- 2x alpha
- Zeta
Which globin chains are found in the following types of haemoglobin:
- HbA
- HbA2
- HbF
- HbA = 2 alpha, 2 beta
- HbA2 = 2 alpha, 2 delta
- HbF = 2 alpha, 2 gamma
What is the normal HbA2 level in a healthy adult?
< 3.5%
main one is HbA
Describe how the haemoglobin levels in utero change.
- 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
What is the difference between sickle cell anaemia and sickle cell disease?
- Sickle cell anaemia - homozygosity for HbS gene
- Sickle cell disease - encompasses homozygous and heterozygous states associated with sickling (including HbSC and HbS/beta thalassemia)
Outline the pathophysiology of sickle cell anaemia.
- 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
What feature of hyposplenism might you seeon a blood film of a patient with sickle cell anaemia?
Howell Jolly bodies
blue arrows - partially sickled, red arrow - sickled
Describe the severity of the following types of sickle cell disease:
- Sickle cell trait
- Sickle cell anaemia
- HbSC
- HbS/beta thalassemia
-
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
- 1 copy HbC, 1 copy HbS
- HbC is abnormal but it is less abnormal than HbS
-
HbS/beta thalassemia
- Severity depends on whether it is beta-0 gene (no globin production) or beta+ gene (some globin production)
- Will be microcytosis due to thalassemia
When is sickle cell anaemia usually diagnosed in the UK?
Why is this necessary
At birth following the Guthrie test
to prevent complications associated with sickle cell that occur in children e.g. hand/foot syndrome and splenic sequestration
mother also screened antenatally
Why does sickle cell anaemia in a child differ from sickle cell anaemia in an adult?
- Mainly because the distribution of red bone marrow (contains haematopoietic precursors) differs
- Red bone marrow is vascular, metabolically active and susceptible to infarction
- Red marrow is in all bones in chilid, in adults confined to axial skeleton and ends of long bones
- Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia - risk in all bones
How is the pattern of bone pain due to infarction different in adults with sickle cell anaemia compared to children?
- Adults - only happens in central skeleton
- Infants/Children - can happen anywhere (including hands and feet causing hand-foot syndrome)
can be prevented if sickle cell diagnosed at birth
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
Define splenic sequestration.
Acute pooling of a large percentage of circulating red cells in the spleen
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
Which age groups tends to be affected by hand-foot syndrome?
< 2 years
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)
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
Which infectious agents are children with sickle cell anaemia particularly vulnerable to?
- Pneumococcus, haemophilus
- Parvovirus B19 (causes aplastic anaemia)
- malaria
encapsulated bacteria
What medication and supplementation is need for sickle cell children
- Vaccination
- Prophylactic antibiotics - penicillin V 3months -5 years
- Folic acid - increased need for haemopoeisis
Why do children with sickle cell anaemia have increased folate demands?
- Hyperplastic erythropoiesis
- Growth spurts
- Reduced red cell lifespan –> so become anaemic very quickly if they have folic acid deficiency
What are the principles of managing sickle cell anaemia?
- Educate parents
- Vaccinate
- Prescribe folic acid and penicillin
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 intermediate form called beta-thalassaemia intermedia, not transfusion dependent but does cause anaemia
List some clinical features of poorly controlled beta thalassaemia major.
- Anaemia → heart failure, growth retardation
- Erythropoietic drive → bone expansion, hepatomegaly, splenomegaly
- Iron overload frorm transfusions → heart failure, gonadal failure
What are the principles of treatment of beta thalassaemia major?
- Accurate diagnosis and family counselling
- Blood transfusion
- Iron chleation
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
haemolytic disease of newborn is congenital but not inherited
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?
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
List some triggers for haemolysis in G6PD deficiency.
- Infections
- Drugs
- Naphthalene
- Fava/broad beans
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
Cells on blood film in G6PD
Heinz bodies
bite cells
raised MCV - high reticulocytes
What are the two main types of acquired haemolytic anaemia?
- Autoimmune haemolytic anaemia
- Haemolytic uraemic syndrome
What are the characteristic features of autoimmune haemolytic anaemia?
- Spherocytes
- Positive DAT
What happens in HUS
what is the cause
- E.coli 0157:H7 –> bloody diarhoead
- Shiga toxin –> thrombosis in small blood vessels
- thromboctopenia, MAHA, AKI
- MAHA - shearing of RBCs into fragments as they pass through fibrin strands within capillaries (intravascular haemolysis)
What are the most common inherited defects of coagulation?
- Haemophilia A - factor VIII deficiency
- Haemophilia B - factor IX deficiency
- Von Willebrand disease
Describe the typical presentation of haemophilia A and B in an infant.
- Bleeding following circumcision
- Haemarthrosis when starting to walk
- Post-traumatic bleeding
clinically A and B are indistinguishable - need to do factor assays
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
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
APTT and PT in haemophilia
prolonged APTT - intrinsic pathway
normal PT - extrinsic pathway
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
What are the principles of treatment of inherited disorders of coagulation?
- Counselling the family
- Treatment of bleeding episodes
- Use of prophylactic coagulation factors
Describe the typical presentation of von Willebrand disease.
- Mucosal bleeding
- Bruises
- Post-traumatic bleeding
as platelets are affected
Inheritance pattern of haemophilia
X-linked recessive
Why do von Willebrand disease and haemophilia A present similarly?
They are both characterised by low level of factor 8
How is von Willebrand disease diagnosed?
- Family history (mainly autosomal dominant(
- Coagulation screen
- Factor 8 assay
- Bleeding time
- Platelet aggregation studies
How is von Willebrand disease treated?
Lower purity factor 8 concentrates
as this also contains vwF
Describe the relative prevalence of haemophilia A and B.
Haemophilia A is 4x more common than haemophilia B
what happens in ITP
Autoantibodies develop against GP IIb/IIIA receptor on platelets –> destroyed by spleen –> thrombocytopenia
Happens after infection
It is a type II herpsensitivity reaction
Describe the typical presentation of ITP.
- Petechiae (non-blanching rash)
- Bruises
- Blood blisters in the mouth - importance for prognosis, more likely to need steroids
diagnosis of exclusion
List some differential diagnoses for ITP.
- Henoch-Scholein Purpura
- Non-accidental injury
- Coagulation factor defect
- Inherited thrombocytopaenia
- Acute leukaemia
List some treatment approcahes for ITP.
- Observation (most common)
- Corticosteroids
- High dose IVIG
- IV anti-RhD (if RhD positive)
Which type of leukaemia is most common in children?
ALL
NOTE: < 1 years old AML is more common than ALL
How is hyposplenism managed?
- Vaccination
- Prophylactic penicillin
- Advice about other risks (e.g. malaria, dog bites)
