Paediatric Haematology Flashcards
What deficiencies are children prone to (2)
Iron deficiency is common in childhood and during adolescent growth spurts, particularly if the diet is sub-optimal
Folic acid deficiency can also occur as a consequence of increased needs
What may occur in children than does not occur in adults during illness (2)
Growth retardation may occur
Puberty delay
What is unusual about the Hb of a neonate
Higher percentage of haemoglobin F than at any other time of life, so disorders of beta globin genes are much less likely to manifest
How does the concentration of glucose-6-phosphate dehydrogenase differ in neonates and adults
50% higher in neonates than in adults
Causes of polycythaemia in the foetus or neonate (3)
Twin-to-twin transfusion
Intrauterine hypoxia
Placental insufficiency
Causes of anaemia in the foetus or neonate (4)
Twin-to-twin transfusion
Fetal-to-maternal transfusion
Parvovirus infection (virus not cleared by immature immune system)
Haemorrhage from the cord or placenta
When does the first mutation that subsequently leads to childhood leukaemia occur
In utero
Pre-leukaemic cells carrying this mutation can even spread from one twin to another
Can leukaemia occur in utero
Yes
This specific type of neonatal leukaemia (also sometimes called transient abnormal myelopoiesis or TAM) differs greatly from leukaemia in older infants or children
What condition is congenital leukaemia particularly common in
Down’s syndrome
What are the key features of congenital leukaemia (3)
The leukaemia is myeloid with major involvement of the megakaryocyte lineage
The most remarkable feature is that it usually remits spontaneously and relapse one to two years later occurs in only about a quarter of infants
There are analogies with other childhood tumours, e.g. neuroblastoma
Define haemoglobinopathy
Any inherited disorder of globin chain synthesis
Thalassaemias
Reduced synthesis of globin chains
Haemoglobinopathies
Synthesis of a structurally abnormal molecule
How are HbA molecules structures
Quaternary structure of 2 alpha and 2 beta
HbA
A2B2
HbA2
A2D2
HbF
A2G2
When is HbA mostly present (4)
Late foetus
Infant
Child
Adult
When is HbA2 present (3)
Infant
Child
Adult
When is HbF present (2)
Foetus
Infant
What is sickle cell disease
Sickle cell disease is a generic term that describes homozygous and compound heterozygous states that are associated with the pathological effects of sickling
It includes sickle cell anaemia (SS) but also compound heterozygous states including SC and S/beta thalassaemia
What is the pathology is sickle cell disease
Hypoxia leads to sickling of the RBCs
How does vascular obstruction occur in sickle cell anaemia
RBC elongates to pass through capillary bed to post-capillary venule
Red cells become adherent to endothelium
More red cells become adherent to endothelium
Obstruction occurs
Sickle cells obstruct the venule and retrograde capillary obstruction occurs
Sickle cell train Hb
BBs
Sickle cell anaemia
BsBs
Sickle cell/haemoglobin C disease
BsBc
Sickle cell/beta thalassaemia
BsBthal
When does sickle cell anaemia manifest
Clinical features become manifest as gamma chain production and haemoglobin F synthesis decrease and Bs and HbS production increase
When is sickle cell anaemia diagnosed
At birth
Guthrie spot
What are the benefits of neonatal diagnosis of sickle cell
Some of the complications can be prevented and others can be anticipated and their effects ameliorated
Why does sickle cell differ in infants/children than in adults (4)
The distribution of red bone marrow (susceptible to infarction) differs - the hand/foot syndrome
The infant still has a functioning spleen - splenic sequestration can occur
The infant has an immature immune system and has not developed immunity to pneumococcus or parvovirus
The infant and child is growing rapidly and has a greater need for folic acid
Vaso-occlusion in the first decade in sickle cell disease (4)
hand-foot syndrome
Acute chest syndrome
Painful crisis
Stroke
What are the complications of splenic sequestration (3)
Severe anaemia
Shock
Possible death
What is splenic sequestration
Splenic sequestration is the acute pooling of a large percentage of circulating red cells in the spleen
The spleen enlarges acutely
The Hb falls acutely and death can occur
Why doesn’t splenic sequestration occur in adults as it can in children with sickle cell disease
This doesn’t happen in older children and adults because recurrent infarction has left the spleen small and fibrotic
What splenic risks are present in adults with sickle cell disease that do not occur in children
Hyposplenism
What infection can be fatal in babies with sickle cell disease
Pneumococcal infection
What virus is a risk in babies/children with sickle cell
Parvovirus B19 - their first exposure leads to pure red cell aplasia
Why is folic acid more important in a child with sickle cell than in a normal child (3)
Hyperplastic erythropoiesis requires folic acid
Growth spurts require folic acid
Red cell life span is shorter so anaemia can rapidly worsen
How is sickle cell anaemia/sickle cell disease managed in infants and children (4)
Accurate diagnosis
Educate parents
Vaccinate
Prescribe folic acid and penicillin
Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count—likely diagnosis?
Parvovirus B19 infection
A 6-year-old Afro-Caribbean boy presents with chest and abdominal pain; Hb is 63 g/l, MCV 85 fl and blood film shows sickle cells—likely diagnosis?
Sickle cell anaemia
What is beta thalassaemia
A condition resulting from reduced synthesis of beta globin chain and therefore HbA
At what age does beta thalassaemia manifest
It becomes apparent in the first 3-6 months of life
When is beta thalassaemia diagnosed
At birth - guthrie spot
What is the importance of beta thalassaemia trait
Harmless clinically, but genetically important
Beta thalassaemia homozygosity clinical features
Anaemia which is fatal in the first few years of life if not transfused
Beta thalassaemia trait
BthalB
Beta thalassaemia homozygosity
BthalBthal
Clinical effects of poorly treated thalassaemia major (3)
Anaemia - heart failure, growth retardation
Erythropoietic drive - bone expansion, hepatomegaly, splenomegaly
Iron overload - heart failure, gonadal failure
How is beta thalassaemi major managed (infant/child) (4)
Accurate diagnosis and family counselling
Blood transfusion
Once iron overload starts to occur, chelation therapy (desferioxamine, deferiprone)
Consideration of the child as an individual and as part of a family
Causes of haemolytic anaemia in children (3)
Inherited
Acquired
Haemolytic disease of the newborn
What defects can cause inherited haemolytic anaemias (4)
Red cell membrane
Haemoglobin molecule
Red cell enzymes—glycolytic pathway
Red cell enzymes—pentose shunt
Principles of haemolytic anaemia diagnosis in children (4)
Is there anaemia?
Is there evidence of increased red cell breakdown (jaundice, splenomegaly, increased unconjugated bilirubin)
Is there evidence of increased red cell production (e.g. increased reticulocyte count, bone expansion)
Are there abnormal red cells?
Red cell membrane defects (haemolytic anaemia) (2)
Hereditary spherocytosis
Hereditary elliptocytosis
Hb defects (haemolytic anaemia)
Sickle cell anaemia
Glycolytic pathway defects (haemolytic anaemia)
Pyruvate kinase deficiency
Pentose shunt defects (haemolytic anaemia)
G6PD deficiency
What can fava beans precipitate
G6PD deficiency episode
What are the two important acquired haemolytic anaemias in children (2)
Autoimmune haemolytic anaemia
Haemolytic uraemic syndrome
What is autoimmune haemolytic anaemia characterised by (2)
Spherocytosis
Positive direct antiglobulin test (Coombs test)
What are the characterisitcs of haemolytic uraemic syndrome (2)
Haemolysis
Uraemia
What type of haemolysis occurs in haemolytic uraemic syndrome
The haemolysis is what is called a microangiopathic haemolytic anaemia
That means that the red cells are damaged in capillaries and are fragmented by the process
Small angular fragments and microspherocytes are formed
Inherited defects of coagulation (3)
Haemophilia A
Haemophilia B
Von Willebrand Disease
Clinical presentation of haemophilia A and B (4)
Bleeding following circumcision
Haemarthroses when starting to walk
Bruises
Post-traumatic bleeding
Differential diagnosis for haemophilia A or B (4)
Inherited thrombocytopenia or platelet functional defect
Acquired defects of coagulation, e.g. autoimmune thrombocytopenic purpura, acute leukaemia
Non-accidental injury
Henoch‒Schönlein purpura
How do you diagnose a coagulation disorder (5)
History of child Family history (X-linked recessive) Coagulation screen Platelet count Assays of specific coagulation factors
Specific history for coagulation disorders in a child (3)
Was there umbilical cord bleeding or bleeding when a heel-prick was done for Guthrie spot?
Was there haematoma formation after vitamin K injection of vaccinations?
Was there bleeding after circumcision?
Management of coagulation disorder in a child (5)
Accurate diagnosis Counselling of 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)
Von Willebrand disease clinical features (3)
Mucosal bleeding
Bruises
Post-traumatic bleeding
Differential diagnosis of VWD
Haemophilia A
Investigations for VWD (5)
Family history (autosomal dominant) Coagulation screen Factor VIII assay Bleeding time?? Platelet aggregation studies
VWD treatment
Lower purity factor VIII concentrations
A 1-year-old boy presents with joint bleeding, Hb, WBC and platelet count are normal, aPTT is prolonged, PT is normal, bleeding time normal—most likely diagnosis?
Haemophilia A
Presentation of autoimmune thrombocytopenic purpura (3)
Petechiae
Bruises
Blood blisters in mouth
Autoimmune TTP differentails (5)
Henoch‒Schönlein purpura Non-accidental injury Coagulation factor defect Inherited thrombocytopenia Acute leukaemia
TTP diagnosis (3)
History
Blood count and film
Bone marrow aspirate (only if there is a very good reason)
TTP treatment (4)
Observation
Corticosteroids
High dose intravenous immunoglobulin
Intravenous anti Rh D (if Rh-positive)
Most common childhood leukaemia
ALL
AML more common below 1 year old
Management of hyposplenism (3)
Appropriate vaccinations
Prophylactic penicillin
Advice to parents RE other risks (malaria, dog bites)
