Paediatric Haematology Flashcards
What are causes of polycythaemia in fetuses and neonates?
Twin-to-twin transfusion
Intrauterine hypoxia (increased EPO synth)
Placental insufficiency (leads to IU hypoxia)
What are unique causes of anaemia in fetuses and neonates?
Twin-to-twin transfusion
Fetal-to-maternal transfusion
Parvovirus infection (virus not cleared by immature immune system)
Haemorrhage from the cord or placenta
What is the type of congenital leukaemia associated with Down’s Syndrome?
Specific type of neonatal leukaemia (AKA. transient abnormal myelopoiesis or TAM) differs greatly from leukaemia in older infants or children.
Often remits spontaneously
May relapse 1-2y
Myeloid with major involvement of megakaryocytic lineage
Newborn babies, in contrast to adults, have:
A. A higher Hb
B. A lower WBC
C. Smaller red blood cells
D. The same percentage of haemoglobin F
A. A higher Hb
Which globin chains are haemoglobin A made of and when is it present?
α2 β2
Late fetus, infant, child + adult
Which globin chains are haemoglobin A2 made of and when is it prevelant?
α2 δ2
Infant, child + adult
Which globin chains are haemoglobin F made of and when is it prevalent?
α2 γ2
Fetus + infant
Why does sickle cell anaemia not manifest at birth?
Clinical features manifest as gamma chain production + HbF synthesis decrease
+
βS + HbS production increase.
Why does sickle cell anaemia present differently in infants and children compared to adults?
- Distribution of red BM (susceptible to infarction) differs: “Hand-foot” syndrome- spreads into limbs + digits
- Infant still has a functioning spleen—splenic sequestration can occur.
- Infant has immature immune system, no immunity to pneumococcus + parvovirus
- Infant growing rapidly with greater need for folic acid
What is splenic sequestration?
Acute pooling of a large % of circulating red cells in the spleen.
Spleen enlarges acutely.
Hb falls acutely + death can occur.
Doesn’t happen in older children + adults because recurrent infarction has left the spleen small + fibrotic
Why does folic acid matter more in a child with sickle cell disease than in a normal child or an adult?
Hyperplastic erythropoiesis requires folic acid.
Growth spurts require folic acid.
Red cell life span is shorter so anaemia can rapidly worsen.
Complications of sickle cell anaemia that are more common in adults than children include:
A. Hand-foot syndrome
B. Hyposplenism
C. Red cell aplasia
D. Splenic sequestration
E. Stroke
B. Hyposplenism
Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count—likely diagnosis?
A. Splenic sequestration
B. Parvovirus B19 infection
C. Folic acid deficiency
D. Haemolytic crisis
E. Vitamin B12 deficiency
B. 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?
A. Sickle cell trait
B. Sickle cell anaemia
C. Sickle cell/beta thalassaemia
B. Sickle cell anaemia
MCV is normal
If C would have microcytosis
What can inherited haemolytic anaemias be due to?
Defects in:
- Red cell membrane
- Haemoglobin molecule
- Red cell enzymes: glycolytic pathway
- Red cell enzymes: pentose shunt
What are the principles of diagnosis of 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?
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?
A. Haemophilia A
B. Haemophilia B
C. Von Willebrand disease
D. Thrombotic thrombocytopenia purpura
E. Has taken mother’s warfarin tablets
A. Haemophilia A
A is more common than B
Bleeding time would be normal in VWD
What is the presentation of (auto)-immune thrombocytopaenic pupura?
Petechiae
Bruises
Blood blisters in mouth
What are ddx for autoimmune thrombocytopaenic purpura?
Henoch‒Schönlein purpura
Non-accidental injury
Coagulation factor defect
Inherited thrombocytopenia
Acute leukaemia
What does rapid growth in childhood predispose to?
Vitamin + mineral deficiency
e.g. Iron + Folic acid
How do kids and adults generally differ in immune response to infections?
Kids: Lymphocytosis
Adults: Neutrophilia
What lymphocytes are common in kids? Why?
Reactive lymphocytes
Frequent encounters with new microbial antigens
How does neonate blood composition differ to adults?
Highest % HbF than any other point: so disorders of B global genes less likely to manifest
G6PD conc. ~50% higher than in adults
What is the fetal circulation susceptible to?
Irradiation or something crossing from the mother into their circulation: drugs, chemicals, antibodies
Anticoagulants: Haemorrhage / Fetal deformity
Antibodies: destroy RBC, WBC, platelets (fathers antigens)
Give an example where breast milk can damage the neonatal blood supply
Lactating woman eating fava beans
G6PD deficient son may suffer haemolysis
When does the first mutation subsequently leading to childhood leukaemia often occur?
In uteru
Pre-leukaemic cells carrying this mutation can spread from one twin to another
What is a haemoglobinopathy?
Genetic disorder with synthesis of a structurally abnormal globin chain molecule
May also refer to any inherited disorder of globin chain synthesis
What is thalassaemia?
Genetic disorder with reduced globin chain synthesis
Describe the presence of haemoglobin in foetal life/ neonates
HbF dominates
HbA rises slightly, then steeply after birth
HbA2 rises later nearer birth, then gradually
What is sickle cell disease?
Group of chronic conditions with sickling of RBCs caused by inheritance of haemoglobin S (HbS)
Describe the pathophysiology of sickling cells
- Hypoxia
- HbS polymerises when deoxygenated, causing sickling of RBCs
- Sickling makes RBC’s more fragile + inflexible- obstruction occurs
- Retrograde capillary obstruction- thrombosis
What is the genotype in Sickle Cell trait? How does this present?
HbAS
Asymptomatic except in conditions that favour sickling (hypoxia, dehydration)
What is Sickle Cell Anaemia?
Homozygosity for HbS
βSβS
What causes formation of HbS?
Point mutation in β globin gene (2α + 2β globin chains form HbA)
Valine subs glutamic acid on position 6= non-polar so insoluble
What is sickle haemoglobin C disease?
Compound heterozygous state
βS + βC
What is sickle cell beta thalassaemia?
Compound heterozygous state
βS + βThal
β0 with no synth of β chain from that gene, have only βS
OR
β+: some HbA produced, but less than normal
What test is used to detect sickle cell disorders at birth?
Guthrie spot
Describe the ages at which children are at differing risk of vaso-occlusion in the first decade
- Hand-foot syndrome: <2y
- Acute chest syndrome: 3y = peak + plateau
- Painful crises: high throughout
- Stroke: more in <10s than adults due to narrow cerebral vessels
What happens as the risk of splenic sequestration decreases?
Risk of hyposplenism increases
Becomes smaller + fibrotic
Spleen important in immunity
Filters out bacteria + parasites
Source of antibody production
What does first exposure to parvovirus B19 in children with sickle cell disease lead to?
Pure red cell aplasia
Arrests maturation of developing red cells in BM
With such reduced lifespan of RBC’s in SCD, results in dramatic fall in Hb
Requires transfusion
What does folic acid matter more in a child with sickle cell disease than in a normal child or adult?
Hyperplastic erythropoiesis requires folic acid
Growth spurts require folic acid
Red cell lifespan is shorter so megaloblastic anaemia can develop + rapidly worsen
Give 4 key components to management of sickle cell disease in the infant + child
Accurate dx
Educate parents
Vaccinate: pneumococcal + meningococcal
Prescribe folic acid + penicillin
What causes beta thalassaemia and when would it first manifest?
Reduced synth of beta globin chain + therefore HbA
First 3-6m
But can perform Guthrie spot at birth
Describe the prognosis of beta thaleassaemia heterozygosity/ trait
Harmless
Important genetically if both parents have the trait
β thal β
What is the genotype in homozygous beta thalassaemia? What is the prognosis?
β thal β thal
Severe anaemia, in absence of blood transfusion is fatal in first few years
What are the clinical effects of poorly treated thalassaemia major?
Anaemia: HF, growth retardation
Increased erythropoietic drive: bone expansion + extra medullary haematopoesis in liver + spleen
Iron overload: HF, gonadal failure
Describe management of beta thalassaemia major in children
Accurate dx + family counselling
Blood transfusion
Chelation therapy once iron overload starts to occur: Desferiozamine
What can cause a non inherited congenital haemolytic anaemia?
Transplacental passage of antibodies cause haemolytic disease of the newborn
e.g. RhD +ve neonate, mother with anti-D
Name 2 red cell membrane defects that can lead to haemolytic anaemia in children
Hereditary spherocytosis
Hereditary elliptocytosis
Name a haemoglobin defect that can lead to haemolytic anaemia in children
Sickle cell anaemia
Name a glycolytic pathway defect that can lead to haemolytic anaemia in children
Pyruvate kinase deficiency
(Rare)
Name a pentose shunt defect that can lead to haemolytic anaemia in children
G6PD deficiency
What is autoimmune haemolytic anaemia characterised by?
Spherocytosis
+ve direct antiglobulin test (Coombs’)
What is haemolytic uraemic syndrome?
thrombotic microangiopathy in which microthrombi, consisting primarily of platelets, form + occlude arterioles + capillaries.
What triad of pathologies arise in HUS? What symptoms do these give rise to?
Thrombocytopenia: petechiae, purpura, mucosal bleeding, prolonged bleeding after minor cuts
MAHA: fatigue, dyspnea, pallor, jaundice
AKI: haematuria, proteinuria, oliguria, anuria
What is found on the blood film in HUS?
Small angular fragments + microspherocytes (Schistocytes)
What is the most common cause of HUS?
EHEC O157:H7 E Coli infection
Usually transmitted via contaminated foods (e.g. undercooked beef or raw leafy vegetables)
List the 3 most common inherited defects of coagulation
Haemophilia A
Haemophilia B
Von Willebrand disease
Give 4 ways in which haemophilia A + B may initially present
Bleeding following circumcision
Haemarthroses when starting to walk
Bruises
Post-traumatic bleeding
Give 4 differentials to haemophilia
Inherited thrombocytopenia or platelet function defect
Acquired defects of coagulation e.g. ITP, acute leukaemia
Non-accidental injury
Henoch‒Schönlein purpura
Give 3 features of Von Willebrand disease presentation. What is the pathophysiology? What differential may you consider?
Mucosal bleeding
Bruises
Post-traumatic bleeding
Defect in platelet function + lack of factor 8
Haemophilia A: factor 8 also reduced
What is the treatment of Von Willebrands disease?
Lower purity factor 8 concentrates
What is the treatment of ITP?
Observation
Corticosteroids
High dose IV immunoglobulin
IV anti-RhD (if Rh+ve)
Describe the prevalence of acute leukaemia in children
ALL most common
AML occurs at all ages, + in <1s is more common than ALL
