Haem: Paediatric haematology Flashcards
Which feature of children predisposes them to nutrient deficiency?
Rapid growth
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
- Higher MCV
How are the enzyme levels in the red blood cells of neonates different to adults?
They have higher concentration of G6PD compared to that of adults
What in foetuses may mask certain haematological disorders
Increased levels of HbF mask disorders involving globin chains (sickle cell, thalassaemias)
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
- Foetal-to-Maternal transfusion
- 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
- 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 a rare type of congenital leukaemia?
Down syndrome
What is another term to describe congenital leukaemia?
Transient abnormal myelopoiesis (TAM)
Describe the usual timeline of congenital leukaemia.
- TAM is a leukaemia within the myeloid lineage - mostly involving megakaryocytes.
- Remits spontaneously within the first 2 months of life
- However, 25% of infants will relapse after 1-2 years as AML.
Differentiate between haemoglobinopathy and thalassaemia.
Haemoglobinopathy = condition resulting in error of globin chains resultin in structural abnormal protein
Thalassaemia = reduced rate of synthesis of one or more globin chains as a result of a genetic defect.
On which chromosomes are the different globin genes expressed? Which types of globin are expressed in either chromosome?
Chromosone 11
- Beta
- Delta
- Gamma
- Epsilon
Chromosone 16
- 2x alpha
- Zeta
we overall have 2 beta copies (1 from each parent) and 4 alpha (2 from each parent)
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
Describe how the haemoglobin levels in utero change.
- HbF predominates throughout foetal life
- After around 32 weeks, there is a rapid increase in HbA production
- At birth, around 1/3 haemoglobin is HbA, th rest being HbF
- By 3-6 months HbF is <5% of total hb.
What is the difference between sickle cell disease, sickle cell anaemia and sickle cell trait?
- Sickle cell disease - encompasses homozygous and heterozygous states associated with sickling (including HbSC and HbS/beta thalassemia)
- Sickle cell anaemia - homozygosity for HbSS gene
- Sickle cell trait - heterozygosity of HbAS gene.
Outline the inheritence pattern of Sickle Cell Disease and describe the genetic mutation.
- Autosomal recessive
- Single base mutation (GAG –> GTG) causing valanine to be in codon 6 of beta chain.
- Valanine causes globin polymerisation which causes sickling.
Outline the pathophysiology of sickle cell anaemia.
- Hypoxia leads to polymerisation of HbS leading to crescent-shaped red blood cells
- Sickling commonly occurs in post-capillary venules
- When passing through these venules, red cells tend to elongate normally to pass through their narrow lumen.
- If the circulation slows down, cells will begin sickling and stickling to the endothelium causing obstruction
What feature of hyposplenism might you seeon a blood film of a patient with sickle cell anaemia?
Howell Jolly bodies
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
- C = defective beta chain - commonly in Africa
-
HbS/beta thalassemia
- Severity depends on whether it is beta-0 gene (no globin production) or beta+ gene (some globin production)
When is sickle cell anaemia usually diagnosed in the UK?
At birth following the Guthrie test
For high risk mothers (ethnicity, Fhx) antenatal genetic testing can be offered.
How is sickle cell anaemia in a child different from sickle cell anaemia in an adult
- Children have predominantly red bone marrow (compared to adult yellow bone marrow). This means most of bone marrow is still highly vascular and pronte to infarction = dactylitis / hand-foot syndrome (only seen in children)
- Children’s spleen is still functioning. Therefore sickle cells cause blockage of endothelial splenic venules causing obstruction and pooling of blood = splenomegaly due to splenic sequestration (due to constant blockage and therefore infarction adults have a small and fibrotic spleen - hyposplenism)
- Children have no immunity or protection to Parvovirus B19 (or pneumoccocus). Therefore at higher risk of infeciton and aplastic crises following Parvovirus B19 infection
- Due to Sickle Cell being haemolysed (because of their structure) there is a high turnover or RBCs and therefore increased demand for folic acid. On top of this children are growing therefore they have an even bigger demand for folic acid, and are at much higher risk of defiicency
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 (were bone marrow is still active and not been mostly substituted by fat (yellow bone marrow))
- Infants/Children - can happen anywhere (including hands and feet causing hand-foot syndrome). This stops occuring at age 2.
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 complications of sickle cell anaemia occur commonly occurs in children over >2 years old (less so in infants)?
- 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
- Parvovirus B19 (causes aplastic anaemia)
In a child with sickle cell disease - what is the tell-tale sign that they are having an aplastic crises (commonly secondary due to Parvovirus B19 infection)
Low reticulocyte count!
Reticulocytes are usually high in SCD (due to high turnover rate). However, they will be low during aplastic crises as stem cells are non-functioning)
How can pneumococcal infection be prevented in a patient with sickle cell anaemia?
- Vaccination
- Prophylactic antibiotics
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 the symptoms Sickle Cell Disease may demonstrate in teens and adults
Same as children = pain crises, anaemia
Teens = impaired growth, gallstones, priapism
Adults = hyposplenism, CKD, retinopathy, iron overload from transfusions
What are the principles of managing sickle cell anaemia?
Acute Management:
* Oxygen
* Opioid analgesia (hit pain management hard)
* Consider blood transfusion (exchange) in severe cases
Chronic Management
* Hydroxycarbamide (commenced in everyone from 9m-12m)
* Penicllin V prophylaxis + Pneumovax + HiB vaccine + Folic acid
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
This is because beta thalassaemia is a spectrum of disease with multiple point mutations which cause decreased beta chain production (and subsequent alpha chains)
Updated terminiology = transfusion dependent thalassaemia (trait) or non-transfusion dependent thalassaemia (severe intermedia, major)
List some clinical features of poorly controlled beta thalassaemia major.
- Anaemia → heart failure, growth retardation
- Erythropoietic drive → bone expansion (frontal bossing), hepatomegaly, splenomegaly
- Iron overload → heart failure, gonadal failure
How is beta thalassaemia diagnosed
Guthrie test at birth
(Can also be diagnosed using Hb electorphoresis)
What are the principles of treatment of beta thalassaemia major?
- Accurate diagnosis and family counselling
- Blood transfusion
- Iron chleation (iron overload is a big complication of beta thalassaemia) - also monitor iron overload in heart and liver.
Types of haemolytic anaemia
Inherited
Acquired (immune vs non-immune)
List some types of inherited haemolytic anaemia.
- Red cell membrane - hereditary spherocytosis, hereditary eliptocytosis
- Haemoglobin molecule - sickle cell anaemia
- Red cell enzyme - Glycolytic pathway - pyruvate kinase deficiency
- Red cell enzyme - Pentose shunt - G6PD deficiency
All are haemolytic anaemias that show at birth/infancy inherited?
No.
Though most congenital anaemias are inherited some can be acquired. For example, haemolytic disease of newborn (acquired through passing of maternal abx through placenta targetting foetal RBCs).
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?
List some triggers for haemolysis in G6PD deficiency.
- Infections
- Drugs
- Fava beans
- Acute stressors / infections
These are oxidants - G6PD helps RBCs make glutathione which protects them from oxidant damage. Deficiency = more susceptible to oxidant damage.
Note that some of these can be absorbed in breastmilk and pass to breast feeding child who if is G6PD deficient can have a crises.
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
Clinical Picture of G6PD deficiency+ Blood film
Prevalent in Africa, Mediterranean and Middle East
Attacks - rapid anaemia and jaundice (following triggers).
Blood film - bite cells and heinz bodies (blue deposits of oxidised Hb)
Diagnosis and Treatment of G6PD deficiency
Diagnosis = enzyme assay for G6PD levels. Done 2-3 months after crises (as young RBCs may have sufficient enzyme)
Treatment = Avoid triggers, transfuse if severe.
What are the two main types of acquired haemolytic anaemia to worry about in children?
- Autoimmune haemolytic anaemia
- Haemolytic uraemic syndrome
What blood film and investigation results would point to a diagnosis of autoimmune haemolytic anaemia?
- Spherocytes
- Positive DAT
What are the most common inherited defects of coagulation?
- Haemophilia A (Factor VIII)
- Haemophilia B (Factor IX)
- Von Willebrand disease
Describe the typical presentation of haemophilia A and B in an infant.
- Bleeding following circumcision
- Haemarthrosis when starting to walk
- Bruises
- Post-traumatic bleeding
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
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
though this is more of a platelet disorder (hence the mucosal bleeding) it also present with coagulation disorder picture (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
- Factor 8 assay
- Platelet aggregation studies
How is von Willebrand disease treated?
recombinant vWF
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
- Blood blisters in the mouth
This occurs ~2wks following a viral infection!
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 as is self limiting)
- Corticosteroids if < 20 or bleeding
- IV anti-RhD (if RhD positive)
