Paediatric Haematology & Malignancy Flashcards
Complications of iron deficiency in childhood
Reduced cognitive and psychomotor performance (in the absence of anaemia)
CBE, iron studies and blood film in iron deficiency anaemia
Low haemoglobin Low MCV Low Ferritin Low serum iron Low transferring saturation High total iron binding capacity Slightly high platelets Microcytosis, hypochromia, poikilocytosis, anisocytosis, target cells (severe anaemia), pencil cells, sometimes nucleated RBCs
Thalassaemia minor diagnosis
Low MCV (much lower than degree of anaemia) Diagnosed on Hb electrophoresis (HbA2 greater than 3.5%) Pre-pregnancy carrier testing of partner is important
Macrocytic anaemia in children
Rare in children
Must be investigated and treated urgently if associated with FTT or neurodevelopmental problems
Symptoms and signs of anaemia in children
Lethargy Irritability Poor feeding Weakness Shortness of breath Pallor Changes in colour or urine, sclera, skin \+/- splenomegaly Flow murmur Signs of cardiac failure
Investigations to perform in microcytic anaemia
Iron studies:
- Low ferritin = iron deficiency
- High ferritin = sideroblastic or anaemia of chronic disease
- Normal ferritin - perform electrophoresis
Haemoglobin electrophoresis
HbA2 greater than 3.5%
Lead levels if at risk (chronic lead poisoning also leads to a microcytic anaemia picture)
Investigations to perform in undifferentiated anaemia
CBE, blood film and reticulocyte
Investigatinos to perform in normocytic anaemia
Reticulocytes:
- increased = haemolysis OR blood loss
Normal reticulocyte count OR abnormalities of other parameters
- hypoplastic/aplastic anaemias (marrow hypoplasias, leukaemia, infiltration)
Investigations for haemolytic anaemia
Blood film - ?RBC abnormalities e.g. spherocytosis Coomb's test G6PD screen Bilirubin Reticulocytes
Management of iron deficiency in children
Dietary modification
- optimise red meat, chicken, green vegetables, fortified foods
- limit cow’s milk to less than 500mL/day
Iron supplementation
Dosing and duration for iron supplementation in child
2-6mg/kg/day
Split into TDS to reduce gastric irritation
Continue for 3 months to replenish stores
Different mixtures of iron supplements for children
Ferrous sulphate
- better absorbed, less tolerated
- e.g. ferro-liquid (6mg.mL elemental iron)
Ferrous gluconate
Expected response to adequate iron supplementation in a child
Hb should rise by 10 each week
Follow up with reticulocyte response in 4 weeks
Prevention of iron deficiency anaemia in children
Introduction of iron containing solids at 4-6 months
Avoid cow’s milk for first 12 months - should only form very minor part of diet up to 24 months
Ensure all formulas and cereals are fortified
Consider supplementation in high risk groups (premmies, low birth weight)
Presentation of G6PD deficiency
Acute haemolysis: jaundice, pallor, dark urine
Acute anaemia: faitgue SOBOE or rest, confusion, lethargy
How severe must haemolysis be to cause anaemia
Greater than 5% of RBC mass per day
Screening and confirmatory tests for G6PD
Fluorescent spot test (most reliable and most sensitive - G6P and NADP to a haemolysate of test RBCs, measure NADPH after by direct fluorescence or nitro blue dye)
Confirmatory:
As above but measures amount of RBC haemolysate, measure NADPH production spectrophotometrically as units per gram of haemoglobin
Management of G6PD
Neonatally: manage as other kinds of neonatal jaundice
Acute presentation:
Haemolysis itself is self-limited
Future avoidance of drugs known to trigger haemolysis and fava beans
Transfusion more likely to be required in children and people with comorbidities causing impaired erythropoiesis
Diseases indicated by bleeding in joints
Haemophilia A and B
Disease processes indicated by mucosal bleeding
Local irritation
Von Willebrane disorder
Platelet dysfunction
Disease processes indicated by bleeding of gums, periosteum and skin
Scurvy
Disease processes indicated by gastrointestinal bleeding in paediatrics
Haemorrhagic disease of the newborn
Liver disease
What is haemorrhagic disease of the newborn?
Vitamin K deficient bleeding in a newborn who has not received a supplemental vitamin K injection
Disease processes indicated by retro-orbital bleeding in a child
Haematological malignancy
Disseminated solid tumour
Disease indicated by child bleeding from shins only
Not pathological on it’s own. Common in pre-schoolers or junior primary children. Ensure to exclude other sites of bleeding
Commonest cause of clotting disorders in children
Immune thrombocytopaenic purpura (ITP)
Epidemiology of ITP (incidence and common age)
4/100,000 per year
2-10 years, peaks at 5 years
Pathophysiology of ITP
Destruction of circulating platelets by anti-platelet IgG autoantibodies causing splenic sequestration
Presentation of ITP
Preceding viral infection 1-2 weeks before presentation
Petechiae, purpura and/or superficial bruising
Rarely causes profuse o mucosal bleeding
Bleeding usually occurs abruptly
Examination otherwise normal (nil lymphadenopathy or splenomegaly)
Diagnosis of ITP
Diagnosis of exclusion
CBE: platelets usually
Management in ITP
Benign and self-limiting in 80%
- Resolves spontaneously in 6-8 weeks
- most children do not require hospitalisation
IF EVIDENCE OF MAJOR HAEMORRHAGE (e.g. intracranial or GI), consider:
- oral prednisolone or IVIG
PLT transfusion reserved for life-threatening haemorrhage (only raises PLT count for few hours)
Advise parents to keep children from playing contact sports while PLT counts very low
Complications of ITP
Intracranial bleed (rare) Chronic ITP - 10-20% of children who develop ITP - PLT count remains low 6m after diagnosis - F>M - slow insidious onset in children >7y - screen for development of SLE Recurrent ITP - rare - thrombocytopaenia at over 3 month intervals
Prevalence of childhood cancer in Australia
1/500 children below 15y (one of the highest incidences in the world)
Most common childhood malignancies
Leukaemia 35% (ALL more) Primary Brain tumours 20% Lymphoma 10% Wilms Tumour 6-8% Neuroblastoma 6-8% Rhabdomyosarcoma 5% Sarcoma of the bone (Osteo- and Ewings) 4%
Long term complications of childhood malignancy
Secondary to cancer and to treatments
20x increased risk to general public to develop second cancer
Organ toxicity (heart)
Growth and hormonal deficiency
Infertility
90% of survivors will develop long term effects
Genetic syndromes associated with childhood malignancy
Leukaemia: - trisomy 21*** - Fanconi anaemia - Neurofibromatosis - Klinefelter syndrome - Noonan syndrome CNS tumours: - Neurofibromatosis*** - Tuberous sclerosis Lymphoma: - Immunodeficiency disorders
Presentations of childhood cancer
- Localised mass
- Disseminated disease (e.g. bone marrow infiltration)
- Pressure on local tissue e.g. lymphma - airway obstruction
Short term effects of chemotherapy
Bone marrow suppression (anaemia, thrombocytopaenia, neutropenia)
Immunosuppression
Gut mucosal damage -> undernutrition and infection
Nausea and vomiting
Anorexia
Alopecia
Long-term side effects of cancer treatment
Renal dysfunction (nephrectomy, cisplatin)
Cardiac dysfunction (doxorubicin, mediastinal radiotherapy)
GH deficiency (Pit RTx)
Bone growth retardation at sites of RTx
Infertility (gonadal RTx, alkylating agents)
Neuropsych (brain surgery or RTx under 5y)
Secondary malignancy (RTx, alkylating agents)
Social/educational disadvantage (absence from school and chronic ill health)
Most common types of leukaemia
ALL 4x as common as AML
80% is precursor B cell
Survival rates in childhood leukaemia
up to 85%
Less in AML (50-75%)
Peak ages of childhood leukaemias
ALL peaks 2-5y
No peak in AML
Poor prognostic factors in childhood leukaemia
Age 10
Tumour load >50x10^9
Particular cytogenic/molecular abnormalities
Persistence of leukaemic blasts in marrow after beginning chemotherapy
high submicroscopic levels of leukaemia detected by PCR
Treatment of ALL and AML
ALL: CTx - induction, consolidation and CNS directed therapy, re-induction and continuation of maintenance therapy
AML: shorter duration of treatment but more intense with hospitalisation, blood products and lower survival rates
What is febrile neutropenia
A single temperature higher than 38.5 OR a sustained temperature higher than 38 for over 1 hour in a patient with confirmed neutropenia or suspected neutropenia (based on CTx in last 14 days)
Highest risk patients for febrile neutropenia
AML treatment Infants with ALL treatment ALL induction ALL delayed intensification Lymphoma induction Allogenic transplant Autologous transplant Re-induction for any chemotherapy
Management of febrile neutropenia
On arrival to hospital:
- Check for signs of sepsis
- IV access, fluid resus (20ml/kg bolus), monitoring
- CBE + differential, Biochem, blood culture, group&hold, urine MCS, lactate
- Commence Abx (within 60 minutes, 30min if signs of sepsis)
- Tazocin if not allergic, continue until cultures -ve 48 hours + afebrile 24h
Full assessment after first dose of Abx (full head-to-toe check for any infections) - investigations as indicated
What is a neuroblastoma?
A solid extra-cranial tumour of primordial neural crest cells
Common in children
Distribution of neuroblastoma
Adrenal gland 40% Abdominal ganglia 25% Thoracic ganglia 15% Cervical ganglia 5% Pelvic sympathetic ganglia 5%
Common presenting symptoms of neuroblastoma
Abdominal mass Abdominal pain or constipation Proptosis Raccoon eyes Horner syndrome Localised back pain Scoliosis Palpable lymph nodes (if >2y)
Investigations in neuroblastoma
CBE: anaemia
Urinary catecholamines: +ve in 90%
Biopsy of mass
Staging: CT/MRI, bone marrow biopsy, bone scan, MIBG scan (90% of neuroblastomas will take up radiolabelled agent)
Survival rates in neuroblastoma
approx 30%
Managemnt of neuroblastoma
Surgery (localised disease)
Intensive CTx, transplant, radiation, maintenance therapy rescue surgery (metastatic)
Syndromes associated with nephroblastoma (Wilm’s tumour)
Beckwith-Wiedemann syndrome
Trisomy 18
Deny-Drash syndrome
Staging of nephroblastoma (Wilm’s tumour)
I-IV
Size (7cm)
Spread from kidneys to vena cava and/or lymph nodes
Number of children with nephroblastoma with bilateral diseae on presentation
5%
Presentation of nephroblastoma
Painless abdominal swelling Abdominal pain Nonspecific symptoms (fever, malaise, anorexia, hypertension, gross haematuria)
Characteristic appearance of nephroblastoma on US/CT/MRI
Intrarenal mass
Arising within kidney and enveloping normal renal tissue
Mixed tissue densities (cystic and solid)
Cure rate for nephroblastoma
over 90% up to stage III
stage IV: 85-90%
Inheritance pattern of haemophilia
X-linked recessive
THUS MUCH MORE COMMON IN MALES
Deficiency in haemophilia
Factor VIII in A (80%)
Factor IX in B (20%)
Clinical features of haemophilia
Moderate-severe forms:
- bleeding into joints, soft tissues and muscles after minor trauma or spontaneously
- haemarthrosis (pain, local swelling and erythema)
- intracranial haemorrhage (rarely)
Mild disease:
- infrequent bleeding usually secondary to trauma
May only be discovered during routine lab tests or by bleeding after major trauma if 25% normal residual activity
Diagnosis of haemophilia
Isolated prolongation of aPTT assay on coagulation studies
Normal platelet counts
Diagnosis made after specific determination of FVIII or FIX clotting activity
Management of haemophilia
Factor replacement therapy (acutely or prophylactically)
- FVIII - cryoprecipitate 3days/week
- FXI - 2 days/week
Avoid meds that reduce platelet function (e.g. aspirin)
Antifibrinolytics (EACA or tranexamic acid) to control bleeding in the gums and GI tract
Complications of haemophilia
Fatal haemorrhage (oropharyngeal spaces, CNS, retroperitoneum) Compartment syndrome (secondary to haematoma into muscle in distal limbs)
Peak age incidence of paediatric leukaemia
Girls: 2y
Boys: 3y
Average treatment time in paediatric leukaemia
Girls: 2y
Boys: 3y
Prevention of meningeal disease in leukaemia
intrathecal chemotherapy
Good prognostic factors in paediatric ALL
Age 3-7y
Female gender
Poor prognostic factors in paediatric ALL
Age less than 1 year or older than 10
WCC greater than 100 at presentation
Philadelphia chromosome
Leading cause of death from ITP
intracranial haemorrhage
Treatment of choice for a child with ITP with massive haemorrhage
Platelet transfusion
IV methylprednisolone
IVIG
+/- splenectomy
Vaccination to cover before undergoing splenectomy
Encapsulated organisms
Pneumococcal
Meningococcal
Haemophilus influenzae B
