Haem: Paediatric haematology Flashcards
Which feature of children predisposes them to nutrient deficiencies?
Rapid growth
What are the main differences between the blood count of neonate and an adult?
- Higher WCC (neutrophils, lymphocytes)
- Higher Hb
- Higher MCV
How are the enzyme levels in the red blood cells of neonates different to adults?
They have 50% of the concentration of G6PD of adults
List some causes of polycythaemia in a foetus.
- Twin-to-twin transfusion syndrome (recepient twin)
- Intrauterine hypoxia
- Placental insufficiency
List some causes of anaemia in a foetus.
- Twin-to-twin transfusion syndrome (donor twin)
- Foetal-to-maternal transfusion (foetomaternal haemorrhage)
- Parvovirus infection
- Bleeding from cord or placenta
When does the first mutation that leads to childhood leukaemia often occur?
In utero
What is transient abnormal myelopoiesis (TAM) and what congential condition is assoicated with?
- congenital leukaemia
- The presence of preleukaemic blasts in the bone marrow and blood of a neonate
- 20% of these children will develop myeloid leukaemia within 4 years
- Associated with Down’s syndrome
What lineage is the myeloid leukaemia associated with TAM?
Megakaryocyte
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.
Conditions characterised by synthesis of structurally abnormal haemoglobin.
NOTE: thalassemias are sometimes considered a form of haemoglobinopathy
On which chromosomes are the different globin genes expressed?
Beta chain - chromosome 11
- Beta
- Delta
- Gamma
- Epsilon
Alpha chain - chromosome 16
- Alpha 1 and 2
- Zeta
What is the globin chain composition of 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%
Which foetal haemoglobins are present in the first 16 weeks?
- Gower 1 (2 zeta, 2 epsilon)
- Gower 2 (2 alpha, 2 epsilon)
- Portland 1 (2 zeta, 2 gamma)
Describe how the different haemoglobin levels in utero and in the first year of life change.
- Haemoglobin Gower 1 and 2 and Portland are present in the first 16 weeks
- HbF predominates throughout most of foetal life and is present until 9 months postpartum
- HbA slowly starts around 2 weeks. After 32 weeks, there is a rapid increase in production
- HbA2 starts being synthesised at 28 weeks
What are the proportions of HbA and HbF at birth?
1/3 HbA
2/3 HbF
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 (specifically mechanims of sickling)
- Hypoxia induces HbS polymerisation and subsequent sickling of RBC
- RBCs become more adeherent to the endothelium and lead vessel occlusion
- This tends to occur in the post-capillary venule
What feature of hyposplenism might you see on a blood film of a patient with sickle cell anaemia?
Howell-Jolly bodies - clusters of DNA (pathognomic of splenic dysfunction)
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
- HbS/beta thalassemia - severity depends on thalassaemia beta chain expression
When is sickle cell anaemia usually diagnosed in the UK?
At birth following the Guthrie test
At what age does sickle cell disease present and why?
- Presents at 5 months
- Clinical features only manifest when HbF levels drop and HbS levels increase
Why do symptoms of 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
- Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia
Hence this is why hand-foot syndrome only occurs in young children
How is the pattern of bone pain due to infarction different in adults with sickle cell anaemia compared to children?
- Adults - only happens in axial skeleton
- Infants/Children - can happen anywhere (particular in hands and feet)
What age group does hand-foot syndrome affect?
<2 years
What is splenic sequestion?
Vaso-occlusion in the spleen leading to acute pooling of blood in the spleen leading to hypovolaemia, shock and death
Why does splenic sequestion only occur in children and not older patients?
- As patients with SCD age, numerous splenic infarcts lead to hyposplenism and a small and fibrotic spleen
- Children typically still have function spleens
How is splenic sequestration managed?
- Blood transfusion
- Splenectomy
Parents should be taught how to palpate the spleen and to seek help when the child is acutely unwell with a large spleen
What does hyposplenism increase the risk of? How is this managed?
- Infection by encapuslated bacteria
- Prevented with vaccinations and prophylactic antibiotics
Which infectious agents are particularly dangerous in children with SCD?
- Pneumococcus
- Parvovirus B19
What can parvovrius B19 cause in SCD?
Aplastic anaemia
How can pneumococcal infection be prevented in a patient with sickle cell anaemia?
- Vaccination
- Prophylactic antibiotics
Why do children with sickle cell anaemia have increased folate demands?
Reduced red cell lifespan
What are the principles of managing sickle cell anaemia in children?
- Monitoring with swift recognition and treatment of complications
- Educate parents
- Vaccinations
- Antibiotic prophylaxis
- Folic acid
Describe the difference in severity of beta thalassaemia trait and beta thalassaemia major.
- Trait - harmless but genetically important (can impact offspring)
- Major - severe anaemia that is tranfusion-dependent
NOTE: there is an moderate form of the disease called beta-thalassaemia intermedia
List some clinical features of beta thalassaemia major.
- Anaemia → heart failure, growth retardation
- Erythropoietic drive → bone expansion, hepatomegaly, splenomegaly
- Iron overload → heart failure, gonadal failure
What are the principles of treatment of beta thalassaemia major?
- Accurate diagnosis and family counselling
- Blood transfusion
- Iron chelation therapy
- Consider child as individual an part of family
Name an iron-chelating drug
Desferrioxamine
List some types of inherited haemolytic anaemia.
- Red cell membrane - hereditary spherocytosis, hereditary eliptocytosis
- Haemoglobin molecule - sickle cell anaemia, thalassaemia
- Glycolytic pathway - pyruvate kinase deficiency
- Pentose shunt - G6PD deficiency
Give an example of acquired congential haemolytic anaemia
Haemolytic disease of the newborn
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?
What type of anaemia would also cause a low reticulocyte count?
Aplastic
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 synthesis
List some triggers for haemolysis in G6PD deficiency.
- Infections
- Drugs
- Naphthalene
- Fava beans
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
What 2 signs would be seen on the blood film of someone with G6PD deficiency?
What are the two important types of acquired haemolytic anaemia in children?
- Autoimmune haemolytic anaemia
- Haemolytic uraemic syndrome
How is AIHA diagnosed?
- Positive DAT
- Spherocytes on blood film
What is the HUS triad?
- Acute renal failure
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
What is microangiopathic haemolytic anaemia?
Intravascular haemolysis of occuring due excessive shear forces in small vessels
What can be seen on blood film that is pathognomic of MAHA?
Schisocytes
What are the most common inherited defects of coagulation?
- Haemophilia A
- Haemophilia B
- Von Willebrand disease
Describe the typical presentation of haemophilia A and B in an infant.
- Haemarthrosis when starting to walk
- Bruises
- Excessive post-traumatic or surgery bleeding
List some differential diagnoses for haemophilia.
- Inherited thrombocytopaenia/platelet defect
- Acquired defects of clotting (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?
- History and examination
- Family history
- Coagulation screen (APTT, PT, fibrinogen)
- Platelet count (rules out platelet causes)
- Assays for specific coagulation factors
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
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
- vWF antigen assay
- Factor 8 assay
- (Bleeding time)
- Platelet aggregation studies
How is von Willebrand disease treated?
- Desmopressin (stimulates vWF release from endothelium)
- Factor VIII or vWF replacement
Describe the relative prevalence of haemophilia A and B.
Haemophilia A is 4x more common than haemophilia B
Describe the typical presentation of ITP.
- Petechiae
- Bruises
- Bleeding from mucous membranes
Typically post-infection
List some differential diagnoses for ITP.
- Henoch-Scholein Purpura
- Non-accidental injury
- Coagulation factor defect
- Inherited thrombocytopaenia
- Acute leukaemia
How is ITP diagnosed?
- History
- FBC and blood film (low platelets with normal to large platelets on film)
- Coagulation screen (normal)
- Bone marrow biopsy (rarely)
List some treatment approaches 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
