haematology and oncology

Question 1

Causes of anaemia in children

Answer 1

• Decreased red cell production
  
  • Iron deficiency (nutritional, occult blood loss, malabsoprtion)
  • Haemoglobinopathy (thalassaemia)
  • Marrow failure (malignant disease, aplasia)
  • Chronic disease (renal failure, inflammation)
• Reduced red cell life span (haemolytic)
  
  • Intrinsic red cell defects (spherocytosis, sickle cell, thalassaemia, G6PD)
  • Immune (autoimmune, incompatibility)
  • Bacterial infections
  • Malaria
  • Hypersplenism, haemolytic uraemic syndrome – heamolysis occurs in reticulo-endothelial system or intravascularly (get haemosiderin or haemoglobin in urine)
• Excessive blood loss
  
  • GI
  • Menstruation
  • Iatrogenic
  • Epistaxis

Question 2

Investigations

Answer 2

• Peripheral blood film – FBC, sickle cells, spherocytes, reticulocytes (increased in haemolysis, haemorrhage; decrease in marrow aplasia), pancytopenia (marrow failure or hypersplenism)
• Red cell indices
  
  • MCV (mean corpuscular volume)
    
    • Microcytic à iron deficiency, thalassaemia
    • Macrocytic à normal in neonates, folate/vitamin B12 deficiency
  • MCHC (mean corpuscular haemoglobin concentration)
    
    • Hypochromic à iron deficiency, thalassaemia
• Serum iron, ferritin and total iron binding capacity – to investigate iron deficiency
• Folate, vitamin B12
• Coombs’ test – positive in haemolysis caused by immunity
• Hb electrophoresis
• Red cell enzyme estimation – glucose-6-phosphate dehydrogenase (G6PD), pyruvate kinase
• Bone marrow aspiration

Question 3

Most common cause of anaemia in childhood

Answer 3

Iron deficiency anaemia

Question 4

Iron requirements

Answer 4

• Term infants have adequate reserves for first 4 months of life
• Preterm infants have limited iron stores and due to higher rate of growth they outstrip their reserves by 8 weeks of age

Question 5

Iron deficiency anaemia

Answer 5

• Causes of dietary iron deficiency
  
  • Infants – delayed mixed feeding, unmodified cow’s milk introduced early
  • Children – poor diet (low socio-economic status, vegetarian diets)
• Clinical features
  
  • Most sub-clinical
  • Irritability, lethargy, fatigue, anorexia, reduced cognitive and psychomotor performance
• Management
  
  • Iron supplements and iron rich diet
    
    • Eg sodium iron edetate
  • Vitamin C increases absorption
  • Continue treatment for 3 months after Hb normalises

Question 6

B thalassaemia major

Answer 6

• Complete absence of B-globin chain production, some mutations allow partial synthesis, HbA cannot be synthesised
• Clinical features
  
  • Present at 6 months with severe haemolytic anaemia, jaundice, failure to thrive and hepatosplenomegaly
  • If untreated, bone marrow hyperplasia occurs à maxillary hypertrophy, skull bossing
• Hb electrophoresis – reveals reduced or absent HbA with increased HbF
• Management
  
  • Regular blood transfusion – maintain Hb >10g/dL
  • Chronic transfusion à iron overload; iron accumulates in heart, liver, pancreas, gonads and skin
  • Chelation therapy with subcutaneous desferrioxamine to promote iron removal
  • Congestive heart failure due to cardiomyopathy occurs around 30
  • Splenectomy and bone marrow transplantation may help

Question 7

B thalassaemia minor

Answer 7

• Mild, hypochromic microcytic anaemia
• Most are asymptomatic
• Diagnosis (differential to IDA)
  
  • Raised HbA2 and mild elevation of HbF on electrophoresis

Question 8

Alpha thalassaemia

Answer 8

• Absence or reduced synthesis of a-globin genes
  
  • A-thalassaemia majo (4 genes deleted) – death in utero
  • Haemoglobin H disease (3 genes deleted) – severe anaemia, persists through life
  • A-thalassaemia minor (2 genes deleted) – mild anaemia
  • Silent carrier (1 gene deleted) – no anaemia, normal RBC indices

Question 9

haemolytic anaemia causes

Answer 9

• Caused by:
  
  • Intrinsic cell defects – spherocytosis, sickle-cell disease, glucose-6-phosphate deficiency (G6PD)
  • Extrinsic defects – Rhesus (Rh) incompatibility, microangiopathy and hypersplenism
• Characterised by:
  
  • Anaemia
  • Reticulocytosis
  • Increased erythropoiesis in bone marrow
  • Unconjugated hyperbilirubinaemia

Question 10

hereditary spherocytosis

Answer 10

• Autosomal dominant disorder – abnormalities in spectrin
• Red cell shape is spherical, life span reduced by early destruction in the spleen
• Clinical features
  
  • Mild anaemia: 9-11g/dL
  • Jaundice: hyperbilirubinaemia
  • Splenomegaly: mild to moderate
• Complications include aplastic crises if parvovirus B19 infection and gallstones
• Diagnosis – spherocytes on blood film, osmotic fragility test (spherocytes rupture more easily than biconcave red cells in hypotonic solutions)
• Management
  
  • Mild disease – folic acid
  • Severe – splenectomy (requires Hib, meningococcal and pneumococcal vaccines before, and prophylactic penicillin for life afterwards)

Question 11

sickle cell disease

Answer 11

• Autosomal recessive mutation in B globin gene
• Sickle cell disease
  
  • HbS differs from HbA (substitution of valine for glutamine) is insoluble in deoxygenated state so aggregates and distorts RBCs
  • Cells have a reduced life span and get trapped in microcirculation causing ischaemia
  • Progressive anaemia with jaundice and splenomegaly
  • Autosplenectomy due to repeated infarction and fibrosis à hyposplenism
  • Hib, meningococcal and pneumococcal vaccines before, and prophylactic penicillin for life afterwards
  • Folate supplements to support erythropoiesis
• Sickle cell trait
  
  • Heterozygous state – confers resistance to falciparum malaria

Question 12

Vaso-occlusive crisis

Answer 12

• Precipitated by infection, dehydration, hypoxia or cold
• Due to microvascular occlusion
• Clinical features
  
  • Hands and feet – dactylitis (<3yrs old)
  • Mesenteric abdomen
  • CNS infarction – stroke, seizure, cognitive defect
  • Avascular necrosis of femoral head – hip pain; may get pain in other long bones
  • Acute chest syndrome – fever, crepitations, chest pain, pulmonary shadowing on CXR
• Management
  
  • Hydroxycarbamide
  • Analgesia – opiates for severe pain
  • Oxygenation
  • Hyperhydration with IV fluids

Question 13

aplastic crisis

Answer 13

Due to parvovirus B19 – sudden reduction in bone marrow function

Question 14

G6PD

Answer 14

• X-linked recessive disorder
• Don’t generate sufficient glutathione so at risk from oxidant agents
• Clinical features
  
  • Neonatal jaundice – most common cause of neonatal jaundice requiring exchange transfusion
  • Intravascular haemolysis – fever, malaise and haemoglobinuria

Question 15

Pyrivate kinase deficiency

Answer 15

• Autosomal recessive
• Infection associated (parvovirus) haemolysis and tolerance of low Hb levels
• Can manage by splenectomy

Question 16

Aplastic anaemia

Answer 16

• Usually idiopathic or inherited eg Fanconi
• Need bone marrow transplant or sometimes immunosuppression/support with blood product transfusions

Question 17

Causes of thrombocytopenia/ platelet function abnormlaities

Answer 17

• Malignancy – leukaemia, lymphoma
• Bone marrow failure – aplastic anaemia, Fanconi’s anaemia, neoplastic infiltration by neuroblastoma/lymphoma/Ewing’s sarcoma
• Inherited platelet conditions
• Microangiopathic haemolytic anaemia – haemolytic uraemic syndrome, congenital thrombotic thrombocytopenia
• Idiopathic thrombocytopenia (ITP)

Question 18

Idiopathic thrombocytopenic purpura

Answer 18

• Most common cause of thrombocytopenia in children
• Usually between 1 and 5yrs
• Clinical features
  
  1. Acute onset bruising/petechiae, epistaxis commonly following a recent viral illness in clinically well child
  2. Platelets <20x10⁹
• Differential diagnosis
  
  1. Acute leukaemia, NAI, HSP
  2. ITP – no atypical features ie absence of systemic symptoms
• Diagnosis
  
  1. FBC – thrombocytopenia but no pancytopenia
  2. Bone marrow aspirate – indicated if atypical features or failure to resolve; excludes marrow infiltration or aplasia; increase in megakaryocytes is characteristic
• Complications
  
  1. Intracranial haemorrhage, chronic ITP
• Management
  
  1. Most children – acute, benign, self-limiting condition; careful observation and limit high impact activities
  2. Platelet transfusion if life threatening bleed (but destroyed rapidly), IV immunoglobulin; steroids; splenectomy if medical therapy fails

Question 19

Henoch schonelin Purpura

Answer 19

• Multisystem vasculitis – due to deposition of IgA containing immune complexes in capillaries, arterioles and venules
• Commonly follows upper respiratory tract infection
• Clinical features (purpura, arthritis, abdo pain)
  
  • Skin – purpura classically over extensor aspects of lower limbs and buttocks
  • Joints – non erosive arthritis (commonly ankles, knees, elbows)
  • GI – colicky abdo pain +/- nausea and vomiting, blood and mucus PR; intussusception may occur
  • Kidneys – haematuria, proteinuria, hypertension
• Clinical diagnosis
• Management
  
  • Symptomatic and supportive
  • Analgesia, monitor renal function, steroids in severe GI disease
• Good prognosis – most children recover in 4-6 weeks; rarely develop chronic renal disease

Question 20

Haemophillia A

Answer 20

• X-linked recessive disorder
• Clinical features
  
  • Spontaneous or traumatic bleeding – subcutaneous, intramuscular, intra-articular
• Diagnosis
  
  • Prolonged APTT, factor VIII deficiency
• Management
  
  • IV infusion of recombinant factor VIII
  • Mild haemophilia – infusion of desmopressin (releases factor VIII from tissue stores)
• Complications
  
  • Progressive arthropathy and disability

Question 21

Haemophillia B

Answer 21

• X-linked recessive disorder
• Clinically similar to haemophilia A but much less common
• Diagnosis
  
  • Prolonged APTT, factor IX deficiency
• Management
  
  • Prothrombin complex concentrate, IV infusion recombinant factor IX

Question 22

von willebrand disease

Answer 22

• Majority autosomal dominant with variable penetrance, some autosomal recessive
• Deficiency or abnormality of von Willebrand factor (VWF) à decreased platelet adhesion
• Clinical features
  
  • Bleeding into skin and mucous membranes (GI, gums, nose), menorrhagia, prolonged bleeding post trauma/surgery
• Diagnosis
  
  • Prolonged APTT, reduced VWF levels
• Management
  
  • Desmopressin, recombinant factor VIII for bleeding episodes

Question 23

DIC

Answer 23

• Intravascular activation of coagulation cascade may be secondary to:
  
  • Damage to vascular endothelium – sepsis, renal disease
  • Thromboplastic substances in circulation – acute leukaemia
  • Impaired clearance of activated clotting factors – liver disease
• Clinical features
  
  • Diffuse bleeding diathesis
  • Bleeding from lungs
  • Bleeding from GI tract
• Diagnosis
  
  • Prolonged INR, APTT and TT; thrombocytopenia; hypofibrinogenaemia; elevated fibrinogen degradation products
• Management
  
  • Treating underlying causes, replacement of platelets and fresh frozen plasma

Question 24

Most common paediatric malignancies

Answer 24

• Leukaemia/lymphoma
• Brain tumours
• Neuroblastoma
• Wilm’s tumour
• Bone tumours

Question 25

ALL

Answer 25

• Ionising radiation – only known cause
• Genetic predisposition – Trisomy 21 (Down syndrome) and Fanconi’s anaemia
• Acute lymphoblastic leukaemia – most common in children
• Clinical features
  
  • Bone marrow failure
    
    • Anaemia – pallor, dyspnoea
    • Low WCC – increased infections
    • Low platelets – bruising, petechiae, epistaxis
  • Bone pain/limp
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Testicular enlargement
  • Cranial nerve palsies, meningism
• Diagnosis
  
  • FBC, blood film (lymphoblasts), bone marrow aspirate, lumbar puncture, coag screen, U&Es, LDH, CXR
• Prognosis
  
  • Overall good prognosis
  • Poor prognosis markers – age<1 >10yrs, male, T cell lineage, WCC at presentation >50, chromosomal abnormalities eg Philadelphia chromosome t(9, 22), failure to rapidly respond to induction chemo
• Management
  
  • Multi drug chemotherapy usually as part of randomised clinical trial +/- radiotherapy +/- bone marrow transplant

Question 26

lymphoma

Answer 26

• Clinical features
  
  • Systemic symptoms – fever, weight loss
  • Lymphadenopathy
• Non-Hodgkin’s lymphoma – younger children
  
  • Hetergenous group with different cells of origin
  • Can develop in immunocompromised children
  • Tend to be aggressive and rapidly growing – most present with mas, intrathoracic usually T cell; peripheral or abdominal usually B cell
  • Treatment – chemotherapy; surgical debulking for abdo tumours
• Hodgkin’s lymphoma – usually adolescents
  
  • Usually painless cervical or supraclavicular lymphadenopathy
  • Metastasis to lungs, liver and bone marrow
  • Diagnose and classify by lymph node biopsy
    
    • Lymphocyte predominant – best prognosis
    • Nodular sclerosing – most common
    • Lymphocyte deplete – rare, worst prognosis
  • Stage by imaging and treat with chemotherapy or radiotherapy if localised

Question 27

Neuroblastoma

Answer 27

• Malignancy of neural crest cells – normally form sympathetic ganglia and adrenals
• Unusual as can regress spontaneously in very young children
• Clinical features
  
  • Abdo mass – usually around 2 yrs
  • Systemic signs, hepatomegaly, unilateral proptosis (mets to eye), opsoclonus-myoclonus (dancing eye, immune response), watery diarrhoea (VIP secretion – paraneoplastic)
• Diagnosis
  
  • Raised urinary catecholamines – vanillylmandelic acid (VMA) and homovanillic acid (HVA)
  • Biopsy or tumour specific scanning
• Management
  
  • Surgical resection, chemotherapy and radiotherapy

Question 28

Wilms tumour

Answer 28

• Arises from embryonal renal cells, usually in toddlers
• Familial forms exist
• Clinical features
  
  • Abdo mass – does not cross midline
  • Abdo pain, haematuria, hypertension
  • 5% are bilateral
• Diagnosis
  
  • CT scan – intrinsic renal mass with solid and cystic areas; biopsy
  • Look for mets – mostly lung and liver
• Management
  
  • Surgical resection, chemotherapy depending on stage and grade and radiotherapy if advanced
• Good prognosis if no mets with 80% cure

Question 29

Bone tumours

Answer 29

• Osteosarcoma (OS) and Ewing’s sarcoma (ES) – most common malignant tumours
• Clinical features
  
  • Persistent bone pain – nocturnal
  • Swelling, deformity
  • Pathological fractures
  • Systemic symptoms associated with ES including fever, anorexia, weight loss
• Diagnosis
  
  • Imaging of lump and distant sites; biopsy
• Management
  
  • OS – chemotherapy, surgery
  • ES – chemotherapy, surgery, autologous stem cell transplant, radiotherapy

Question 30

Brain tumours

Answer 30

• Types
  
  • Astrocytomas, primitive neuroectodermal tumours, craniopharyngoma
  • Most common type is secondary – rare in children
• Clinical features
  
  • Raised ICP – early morning headache becoming more severe, vomiting, papilloedema (late), in extreme – hypertension, bradycardia, abnormal respirations (Cushing’s triad), reduced GCS
  • Focal seizures
  • Neurological signs
  • Endocrine disturbance – pituitary gland impaction
  • Raised orbitofrontal cortex – developmental delay/regression
• Investigations
  
  • If brain tumour suspected – CNS imaging; often CT but MRI is investigation of choice
  • Tumour biopsy
  • Tumour markers
  • Endocrine screen
  • CSF – cytology and tumour markers
• Management
  
  • Resuscitation as necessary – APLS
  • Neurosurgical referral – consider CSF diversion and resection/biopsy
  • Dexamethasone – reduce peritumour oedema
  • Chemotherapy, radiotherapy