Paeds malignant diseases and haematology (ILA 1) Flashcards
What is the most common leukaemia in children?
Acute lymphoblastic leukaemia accounts for 80% of cases in children
What is leukaemia?
cancer of the white blood cells
overproduction of immature white blood cells -> inhibit production of normal cells in bone marrow -> infiltrates organs -> organ failure
How does leukaemia commonly present?
causes bone marrow infiltration which leads to…
- anaemia - pallor, lethargy
- thrombocytopenia - bruising, nose bleeds
- neutropenia - frequent infection
- bone pain
List poor prognosis factors for leukaemia
child <2 y/o or >10 y/o B/T cell surface markers WBC >20 x 10^9/L non caucasian male sex
Which cells would you expect to see in ALL?
BLAST CELLS
How is ALL diagnosed?
FBC - anaemia, thrombocytopenia, neutropenia, blast cells
bone marrow examination *
How is ALL treated?
REMISSION INDUCTION - correct anaemia, hydration, treat infections
INTENSIFICATION - intensive chemo
What are the most common brain tumours in children?
astrocytoma **
(most malignant form is a glioblastoma multiforme)
most commonly infratentorial - located below the tentorium cerebelli
Outline the symptoms that you might see in a brain tumour
symptoms of raised intracranial pressure…
- vomiting (early in morning)
- headache
- abnormal eye movements - papilloedema, squint, nystagmus
- seizures
- problems with balance/ walking
- lethargy
- developmental delay/ problems at school / delayed puberty
List the signs of a tumour in the cortex
seizures
hemiplegia
focal neurological signs
List the signs of a tumour in the midline
visual field loss = bitemporal hemianopia
pituitary failure
List the signs of a tumour in the cerebellum / 4th ventricle
truncal ataxia
coordination difficulties
abnormal eye movements
List the signs of a tumour in the brainstem
cranial nerve defects
pyramidal tract signs
ataxia
List the signs of a tumour in the spine
peripheral weakness of limbs
back pain
bladder/ bowl dysfunction
how is a brain tumour diagnosed?
MRI
When would you consider scanning a child presenting with a headache?
- papilloedema, visual loss
- neurological signs
- <2 y/o
- headache in early morning with vomiting preceding
- short stature
- neurofibromatosis
How does hodgkin lymphoma commonly present?
painless lymphadenopathy ***
- commonly in the neck
- lymph nodes larger and firmer
several month history
systemic symptoms - tiredness, weight loss, sweating
How is hodgkins lymphoma diagnosed?
lymph node biopsy
Which lymphoma presents more commonly in childhood?
non hodgkin lymphoma more common in childhood
How does non- hodgkin lymphoma commonly present?
mediastinal mass which can cause SVC obstruction - dyspnoea, facial swelling, flushing, distended veins
bone marrow infiltration
What are the signs of bone marrow infiltration?
- anaemia
- neutropenia
- thrombocytopenia
- bone pain
How do neuroblastomas present?
- abdominal mass - large, hepatomegaly
- bone pain
- limp
- bone marrow suppression
- malaise
- weight loss
Where do neuroblastoma arise from?
arise from neural tissue in the adrenal medulla and sympathetic nervous system
What is the prognosis for a neuronblastoma?
poor - often present late at advanced state and metastatic
What is the most common renal tumour in children and when do they present?
Wilms tumour = nephroblastoma
usually present before the age of 5
where do wilms tumour arise from?
embryonal renal tissue
how do wilms tumour commonly present?
large abdo mass
haematuria
How are nephroblastomas diagnosed?
ULTRASOUND +/- CT +/- MRI
How are nephroblastomas treated?
- chemotherapy - prior and after surgery
- delayed nephrectomy
- radiotherapy
What is the most common form of soft tissue sarcoma in childhood?
rhabdomyosarcoma
Where do soft tissue sarcomas arise from?
cancers of connective tissue e.g. muscle or bone
rhabdomyosarcoma originate from primitive mesenchymal tissue
How do soft tissue sarcomas present?
head and neck most common site of disease - proptosis, nasal obstruction, bloodstained nasal discharge
Genitourinary tumours - dysuria, urinary obstruction, scrotal mass, vaginal discharge
How does a child with a bone tumour present?
usually a well child
persistent localised bone pain
Which investigations should be carried out for bone tumours?
bone scan
x-ray
MRI
What are the causes of retinoblastoma?
family history!! - all children with families with it are screened, RB1 gene, autosomal dominant
multimodal therapy
sporadic
How does retinoblastoma present?
white pupillary reflex
squint
Where do germ cell tumours arise from?
arise from primitive germ cells which migrate from yolk sac endoderm to form gonads in the embryo
Which markers are used to diagnose germ cell tumours?
alpha fetoprotein
beta hCG
What are the 2 types of primary malignant liver tumours?
hepatoblastoma (65%) hepatocellular carcinoma (25%)
What are the common symptoms for a liver tumour?
- abdominal distension
- abdominal mass
- jaundice
- pain
How are liver tumours diagnosed?
elevated serum alpha fetoprotein
What are the symptoms of langerhans cell histiocytosis?
- bone lesions - pain, swelling, fracture
- diabetes insipidus
- systemic LCH - seborrhoea rash, soft tissue involvement
How is langerhans cell histiocytosis diagnosed and what would you see?
x-ray - lytic lesions with well defined border in bones, often involving skull (punched out osteolytic lesions)
What is langerhans histiocytosis?
abnormal proliferation of histiocytes
What are the most common cancers in children before the age of 5?
ALL
neuroblastoma
wilm tumour
retinoblastoma
What are the most common cancers in children at school age?
ALL
brain tumours
What are the most common cancers in adolescent children?
ALL
hodgkin lymphoma
malignant brain tumours
soft tissue sarcomas
Outline the ranges of Hb to classify as anaemia in neonates, infants and children
neonate <14
1-12 months <10
1-12 years <11
Define anaemia
Hb level below the normal range
How can anaemia be classified by mechanism?
- reduced red cell production
- increased red cell destruction
- blood loss
List the causes of reduced red cell production
RED CELL APLASIA
parvovirus B19 infection
diamond blackfan anaemia
leukaemia
INEFFECTIVE ERYTHROPOIESIS iron deficiency folic acid deficiency chronic inflammation chronic renal failure
List the causes of increased red cell destruction
RED CELL MEMBRANE DISORDERS
hereditary spherocytosis
RED CELL ENZYME DISORDERS
glucose 6 phosphate dehydrogenase deficiency
HAEMOGLOBINOPATHIES
sickle cell disease
thalassaemia
IMMUNE
haemolytic disease of the newborn
List the causes of blood loss
FETAL MATERNAL BLOOD LOSS
CHRONIC GI BLOOD LOSS
meckel diverticulum
INHERITED BLEEDING DISORDERS
von willebrand disease
List some simple diagnostic tests to approach anaemia in children
- reticulocyte level
if low -> red cell aplasia
if high -> look at bilirubin - bilirubin levels
if normal -> blood loss or ineffective erythropoiesis
if high -> haemolysis
Outline the causes of iron deficiency anaemia
- INADEQUATE INTAKE
1 y/o needs 8mg/day of iron - MALABSORPTION
- BLOOD LOSS
Why is it common for children to have iron deficiency anaemia?
children need additional iron for the increase in blood volume accompanying growth and to build their iron stores
When would children experience symptoms with iron deficiency anaemia?
when Hb <6/7 ..
tired
slow feeding
pallor
How is iron deficiency anaemia diagnosed?
microcytic hypochromic anaemia
low serum ferritin
How is iron deficiency anaemia managed?
- dietary advice - eat foods high in iron e.g. red meat, oily fish, liver
- supplement with oral iron
Sytron=sodium iron edetate or Niferex=polysaccharide iron complex
continue taking until iron levels normal and then for another 3 months
Define haemolytic anaemia
increased red cell destruction in the circulation/ liver/spleen causing reduced red cell lifespan
How is haemolytic anaemia caused?
- red cell membrane disorders
e. g. hereditary spherocytosis - red cell enzyme disorders
e. g. glucose-6-phospahte dehydrogenase deficiency - haemoglobinopathies
e. g. beta thalassaemia, sickle cell disease
How does haemolytic anaemia present?
anaemia !
hepatomegaly and splenomegaly
List some diagnostic clues indicating haemolytic anaemia
unconjugated bilirubinaemia
urinary urobilinogen increased
raised reticulocyte count
Why is anaemia common in the newborn?
there is a fall in Hb from birth so normal levels reached at about 2 months:
- decreased RBC production
- shorter lifespan of neonatal RBCs
- more fragile RBCs
- switch from HbF to HbA
How is hereditary spherocytosis inherited?
autosomal dominant
but 25% have no family history
How does hereditary spherocytosis present?
jaundice **
anaemia
splenomegaly
gallstones (because of increased bilirubin excretion)
How is hereditary spherocytosis diagnosed?
blood film
How is hereditary spherocytosis managed?
- oral folic acid
- vaccinations
- lifelong dairy penicillin prophylaxis
- splenectomy (if symptomatic)
how is G6PD deficiency inherited?
x-linked
Where does G6PD deficiency have the highest prevalence?
central africa
mediterranean
middle/far east
How does G6PD deficiency present?
- neonatal jaundice - first 3 days of life
- acute haemolysis
- chronic non spherocytic haemolytic anaemia
How do acute haemolytic events present and how can they be triggered?
precipitated by: infection, broad beans, drugs (sulphonamides, nitrofurantoin, aspirin)
fever pallor jaundice malaise dark urine
How is GP6D deficiency diagnosed?
measuring G6PD activity in red blood cells
Define sickle cell anaemia
child is homozygous for HbS
they have small amounts of HbF, no HbA, so virtually all of Hb is HbS
Define sickle cell trait
child is heterozygous for HbS so 40% of Hb is HbS
carriers of the disease so ASYMPTOMATIC
How is sickle cell disease inherited?
autosomal recessive
Where has the highest prevalence of sickle cell disease?
tropical africa
caribbean
Describe the pathology behind sickle cell disease
HbS polymerises within RBC to form rigid tubular spiral bodies which deform the RBC into a sickle shape
the sickle shape causes:
- reduced lifespan of Hb
- blood vessel occlusion resulting in ischaemia in organs and bones
Outline the symptoms of sickle cell disease
- anaemia (Hb 6-10 g/dl)
jaundice - increased susceptibility to infection
e. g. pneumococci, H.influenza - vaso-occlusive crises
hand foot syndrome: dactylics with swelling and pain of fingers and feet - acute anaemia
haemolytic crises, aplastic crises, sequestration crises - splenomegaly
6. long term problems short stature, delayed puberty heart failure renal dysfunction stroke cognitive problems gallstones
How is sickle cell disease managed?
- prophylactic penicillin and immunisation
- folic acid
- good hydration and nutrition
- hyroxyurea OR bone marrow transplant
Where is beta thalassaemia most prevalent?
india
mediterranean
middle east
What is beta thalassaemia and how is it classified?
severe reduction in production of beta global and reduction of HbA
- beta thalassaemia major - severe, death early teens
- beta thalassaemia intermedia - asymptomatic
What is alpha thalassaemia major?
deletion of all 4 alpha globin genes
fatal in utero within hours of birth
How does beta thalassemia major present?
severe anaemia + jaundice
failure to thrive
extra medullary haemopoiesis
How is beta thalassemia major managed?
monthly lifelong blood transfusions!!!
+ iron chelation with desferrioxamine (prevent chronic iron overload)
What is bone marrow failure syndrome?
“aplastic anaemia”
reduction or absence of all 3 main lineages in the bone marrow leading to peripheral blood pancytopenia
What is the triad for the presentation of bone marrow failure?
- anaemia
e. g. pallor, tired - thrombocytopenia
e. g. bruising, bleeding - neutropenia
e. g. infection
How are bone marrow failure syndromes caused?
ACQUIRED
viruses e.g. hepatitis
drugs e.g. chemotherapy and toxins
idiopathic
INHERITED (RARE!!!)
Fanconi anaemia
Schwachmai-Diamond syndrome
How is fanconi anaemia inherited and what are its complications?
autosomal recessive
congenial anomalies e.g. short stature, renal malformations
can progress to ALL
Define haemostasis
normal process of blood clotting
List the 5 main components of haemostasis
- coagulation factors
- coagulation inhibitors
- fibrinolysis
- platelets
- blood vessels
How are thrombosis in children usually caused?
95% of VTE events are secondary to underlying disorders with hyper coagulable states “thombophilia”
e.g. protein C deficiency, protein S deficiency, anti thrombin deficiency, factor v leiden, prothrombin gene G20210A mutation
How are children with VTE managed?
must be screened for inherited thrombophilia disorders e.g. PCR, prothrombin gene mutations, assays
How are haemophilia A/B inherited?
X linked
what are haemophilia A and B deficient in to cause their symptoms?
Haemophilia A - FVIII deficiency
Haemophilia b - FIX deficiency
How does haemophilia commonly present?
spontaneous, recurrent bleeding into joints and muscles
often presents when start to walk at 1 y/o -> arthralgia
How might a neonate with haemophilia present?
intracranial haemorrhage
bleeding post circumcision
prolonged bleeding from heel stick/ venipuncture
Outline the 2 major roles of VWF?
- facilitates platelet adhesion to damaged endothelium
2. carrier protein for FVIIIC
What is VWF disease?
qualitative or quantitative deficiency in VWF causing defective platelet plug formation and deficiency of FVIIIC
How is VWF disease inherited?
autosomal dominant
What is the most common VWF disease?
type 1 - mild and asymptomatic
How does VWF disease present?
bruising
excessive, prolonged bleeding after surgery
mucosal bleeding e.g. menorrhagia
How is type 1 VWF disease treated?
DDAVP (desmopressin)
Define mild, moderate and severe thrombocytopenia
mild = 50-150 moderate = 20-50 severe = <20
PLATELET COUNT X10^9/L
List the symptoms of thrombocytopenia
bruising
petechiae
purpura
mucosal bleeding e.g. bleeding from gums when brushing teeth
What is commonest cause of thrombocytopenia in childhood?
Immune thrombocytopenia (ITP)
How is ITP caused?
destruction of circulating platelets by anti platelet IgG autoantibodies
How does ITP present?
present age 2-10 years with onset of 1-2 weeks after a viral infection
petechia, purpura and bruising
Describe the prognosis of ITP
80% is acute, benign and self limiting
can be managed at home and don’t need treatment
What is disseminated intravascular coagulation?
activation of the coagulation pathway leading to diffuse fibrin deposition in the micro-vasculature and consumption of coagulation factors and platelets causing microvascular thrombosis
What can cause DIC?
severe sepsis *
shock e.g. trauma, burns
When would you suspect a diagnosis of DIC?
thrombocytopenia prolonged prothrombin time prolonged APTT low fibrinogen D-dimers haemolytic anaemia
How is DIC managed?
treat underlying cause!
intensive care - fresh frozen plasma, cryoprecipitate, platelets
