Paediatric Haematology Flashcards
What are some key points to remember when interpreting paediatric blood tests
Pre-pubertal children differ physiologically from adults
What is normal differs from the adult
There are no gender differences before puberty
Give a reason why the range of diseases seen in children differ from in adults
The first encounter with a pathogenic microorganism often occurs in childhood (whereas adults often have some degree of immunity)
What may rapid growth of children predispose them to?
Vitamin or mineral deficiency
Iron deficiency is common in childhood and during the adolescent growth spurt, particularly if diet is sup-optimal
In what way does a child respond to an infection differently to adults?
Children are more likely to develop lymphocytosis
‘Reactive’ lymphocytes are also common because of the frequent encounters with new microbial antigens
Give an example of a haematological disease that can cause endocrinological dysfunction and growth retardation in children?
Beta thalassaemia (and its treatments) result in iron overload
What is a key haematological difference in neonates?
Type of haemoglobin
gamma haemoglobin
What enzyme levels in red cells are different in neonates?
glucose-6-phosphate dehydrogenase (G6PD) concentration is 50% than in adults
What may cause polycythaemia in the foetus or neonate?
Twin-to-twin transfusion
Intrauterine hypoxia
Placental insufficiency
What may cause anaemia in the foetus or neonate?
Twin-to-twin transfusion
Foetal-to-maternal transfusion
Parvovirus infection (not cleared by immature immune system)
Haemorrhage from the cord or placenta
What else may affect the blood of the foetus?
Irradiation
Something crossing from the mother to the infant e.g.
Drugs - anticoagulant drugs can cause haemorrhage or foetal deformity
Antibodies can destroy red cells, white cells or platelets
With what genetic syndrome does congenital leukaemia occur?
Down’s Syndrome
What is another name for congenital leukaemia?
Transient abnormal myelopoiesis (TAM)
What are the features of congenital leukaemia?
Myeloid with major megakaryocyte lineage
Usually remits spontaneously and relapse one to two years later occurs in 25%
Analogies with other childhood tumours e.g. neuroblastoma
What are thalassaemias?
Genetic disorder resulting in reduced synthesis of globin chains
What are haemoglobinopathies?
Genetic disorder resulting in synthesis of a structurally abnormal globin chain
What globin chains are present in haemoglobin A and when is it present?
alpha2, beta2
Late foetus, infant, child and adult
What globin chains are present in A2 haemoglobin and when is it present?
alpha2, delta2
Infant, child and adult
What globin chains are present in F haemoglobin and when is it present?
alpha2, gamma2
Foetus and infant
What is sickle cell disease?
Generic term that describes homozygous and compound heterozygous states that are associated with the pathological effects of sickling
What is sickle cell anaemia?
SS
Homozygous for sickle cell
Why does sickle cell anaemia not clinically manifest at birth?
Clinical features become manifest as gamma chain production and haemoglobin F synthesis decrease and betaS and haemoglobin S production increase
How do we test for sickle cell disease in neonates?
Guthrie spot
Why does sickle cell anaemia in the infant and child differ from the same disease in adults?
Initially due to presence of haemoglobin F
The distribution of red bone marrow (susceptible to infarction) differs - extends right down the long bones into hands and feet
The infant still has a functioning spleen - splenic sequestration can occur
What is the hand-foot syndrome?
Painful swelling due to infarction of underlying bone
What vaso-occlusion occurs in the first 2 years of life?
Hand-foot syndrome
What vaso-occlusions increase with age?
Acute chest syndrome
Painful crises
Stroke
What is splenic sequestration?
Cells sickle in the spleen –> severe anaemia –> shock and possible death
Why does splenic sequestration not occur in older children and adults?
Recurrent infarction has left the spleen small and fibrotic
What are the risks of a small and fibrotic spleen?
Increased risk of infection
Hyposplenism
What happens in children with haemoglobinopathies and thalassaemias if they get parvovirus infection?
Acute severe anaemia
Why do infants with haemoglobinopathies and thalassaemias require more folic acid?
Hyperplastic erythropoiesis requires folic acid
Growth spurts require folic acid
Red cell life span is shorter so anaemia can rapidly worsen
What are the key elements of management of haemoglobinopathies and thalassaemias in children?
Accurate diagnosis
Educate parents
Vaccinate
Prescribe folic acid and penicillin
What is beta thalassaemia?
Condition resulting from reduced synthesis of beta globin chain and therefore haemoglobin A
At what age would beta thalassaemia first become apparent?
3-6 months of life
What happens in homozygous beta thalassaemia?
Severe anaemia that in the absence of blood transfusion is fatal in the first few years of life
What are the clinical effects of poorly treated thalassaemia major?
Anaemia –> heart failure, growth retardation
Erythropoietic drive –> bone expansion, hepatomegaly, splenomegaly
Iron overload –> heart failure, gonadal failure
What is the management of beta thalassaemia major?
Accurate diagnosis and family counselling
Blood transfusion
Monitoring for narrowing of cerebral vessels
Chelation therapy for iron overload
What drugs can be used for chelation therapy in iron overload?
Desferioxamine
Deferiprone
Inherited haemolytic anaemias can be due to what defects?
Red cell membrane Haemoglobin molecule Red cell enzymes - glycolytic pathway Red cell enzymes - pentose shunt Other rare conditions
What are the principles of diagnosis in haemolytic anaemias?
Is there anaemia?
Is there evidence of increased red cell breakdown e.g. 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
What haemolytic anaemias occur in children?
Red cell membrane defects: hereditary spherocytosis, hereditary elliptocytosis
Glycolytic pathway defects: pyruvate kinase deficiency
Pentose shunt defects: G6PD deficiency
What are the acquired haemolytic anaemias in children?
Autoimmune haemolytic anaemia
Haemolytic uraemia syndrome (HUS)
What are the features of autoimmune haemolytic anaemia?
Spherocytosis
Positive direct antiglobulin test (Coombs’ test)
What are the features of haemolytic uraemia syndrome?
Usually the result of infection by a pathogenic Escherichia coli
It is a microangiopathic haemolytic anaemia - red cells are damaged in capillaries and are fragmented by the process forming small angular microspherocytes
When should Glucose-6-phosphate dehydrogenase deficiency be suspected?
Prolonged neonatal jaundice or when a baby, infant or child develops sudden pallor and jaundice and the blood count and film show anaemia and the presence of irregularly contracted cells
List inherited defects of coagulation
Haemophilia A
Haemophilia B
Von Willebrand disease
What is the presentation of haemophilia A and B
Bleeding following circumcision
Haemarthroses when starting to walk
Bruises
Post-traumatic bleeding
What are the differential diagnoses for bleeding/bruising in children?
Inherited thrombocytopenia or platelet function defect
Acquire defects of coagulation e.g. autoimmune thrombocytopenic purpura, acute leukaemia
Non-accidental injury
Henoch-Schönlein purpura
What is required to make diagnosis of inherited defects of coagulation?
History of child Family history (X-linked recessive or not) Coagulation screen Platelet count Assays of specific coagulation factors
What is the management of inherited defects of coagulation?
Accurate diagnosis
Counselling of family
Treatment of bleeding episodes
Use of prophylactic coagulation factors
What is the presentation of von Willebrand disease?
Mucosal bleeding
Bruises
Post-traumatic bleeding
What is needed for diagnosis of von Willebrand disease?
Family history (mainly autosomal dominant)
Coagulation screen
Factor VIII assay
Platelet aggregation studies
What is the treatment for von Willebrand disease?
Lower purity factor VIII concentrates
What is autoimmune thrombocytopenic purpura (ITP)?
Decrease in the number of platelets in the blood, often triggered by an infection
What is the presentation of ITP?
Petechiae
Bruises
Blood blisters in mouth
What are the DDx for ITP?
Henoch-Schönlein purpura Non-accidental injury Coagulation factor defect Inherited thrombocytopenia Acute leukaemia
How is ITP diagnosis made?
History
Blood count and film
Bone marrow aspirate - if there is a very good reason
What is the treatment for ITP?
Observation
Corticosteroids
High dose IV immunoglobulin
IV anti-RhD if Rh-positive
When do different acute leukaemias present in children?
Acute leukaemia in children is mainly acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia also occurs at all ages and below the age of 1 year it is more common than ALL
