Haematology and Oncology Flashcards
How does iron deficiency cause anaemia? -it leads to ineffective ___
-ineffective erythropoiesis/red cell production
Name 3 causes of anaemia due to red cell aplasia in children;
- parovirus b19 infection
- diamond blackfan anaemia (congenital red cell aplasia)
- Fanconi anaemia
- aplastic anaemia
- leukaemia
- transient erythroblastopenia of childhood
What are the main causes of iron deficiency anaemia (IDA) in children?
- inadequate intake
- malabsorption
- blood loss
Name a couple of sources of iron intake in an infant:
- breastmilk (low content but 50% absorbed) /infant supplemented formula
- cow’s milk (higher content but only 10% absorbed)
- solids introduced at weaning e.g. (fortified) cereals (only 1% absorbed)
What are the clinical fts of IDA in children?
- asymptomatic until Hb <70g/L
- tiring easily
- infants feed more slowly
- pallor: conjunctivae, tongue, palmar creases
- ‘pica’ e.g. soil, chalk, gravel eating
What blood results are diagnostic of iron deficiency anaemia?
- microcytic hypochromic anaemia (low MCV and MCH)
- low serum ferritin
What are 2 other differentials (other than IDA) in a child with a microcytic anaemia:
- beta thallassaemia trait (NB: alpha thallass have microcytic MCV but most are not anaemic
- anaemia of chronic disease
Management of IDA in children:
- dietary advice
- oral iron supplementation (sytron or niferex) these should rise the Hb by 10g/L per week
If after oral iron, anaemia is not improving and history suggests there is a non-dietary cause of IDA, what differentials could be investigated?
- malabsorption due to coeliac disease
- chronic blood loss due to Meckel’s diverticulum
Sub-clinical iron deficiency (e.g. low ferritin but not anaemic) is controversial to treat suggest an adv, a disadv and a solution in the management of this:
- adv: if untreated, IDA can cause behavioural/intellectual function decline
- disadv: if orally treated, there is a risk of poisoning which is v toxic
- solution: give dietary advice to increase iron intake and its absorption
What pattern of inheritance is sickle cell disease?
Autosomal recessive
HbS (sickle cell) arises as a result of a point mutation in codon _ of the __ ___ gene.
This causes a change in amino acid encoded from glutamine to ____
codon 6 of the beta-globin gene
–> valine
State the main types of sickle cell disease(4):
- sickle cell anaemia (HbSS)
- HbSC disease
- Sickle B-thalassaemia
- Carriers/Sickle Cell Trait
Pathogenesis of sickle cell disease in one sentence. (HbS … –> sickle shape)
-HbS polymerises within RBCs forming rigid tubular spiral bodies which deform red cells into a sickle shape
How do the irreversibly sickled cells lead to organ/bone ischaemia? What exacerbates this?
- they have a reduced lifespan
- they may be trapped in microcirculation (–>vaso-occlusion)
- leads to ischaemia
- exacerbated by: low O2, dehydration, cold
What is one of the most important factors that affects severity of Sickle Cells disease and varies between phenotypes affecting disease severity?
-amount of HbF (most pts have levels <1% but some genetic variations with 15%+ have much less severity)
Prophylaxis is part of the management of sickle cell disease, what may this involve?
- full immunisation (susceptible to infections esp. encapsulated e.g. strep pneumo, Hib due to functional asplenia)
- pneumococcal, Hib and meningococcal vaccinations
- daily oral penicillin in childhood (protects vs. all pneumococcal subgroups)
- OD oral folic acid (increased demand arises from the chronic haemolytic anaemia)
- avoid exposure to cold/dehydration/undue stress/hypoxia
Why do sickle cell pts have hypospenism/functional asplenism? What is an emergency related to this?
- secondary to chronic sickling and microinfarction in the spleen
- sequestration crisis: sudden splenic enlargement, abdo pain and circulatory collapse from accumulation of sickled cells in spleen
Priapism in sickle cell children needs to be treated quickly with _____ ____ as it may lead to _____ of the ___ ___ and subsequent ___ ___
- exchange transfusion
- fibrosis of the corpus cavernosa
- erectile impotence
Name 5 long term complications of sickle cell disease:
- short stature, delayed puberty
- stroke, cognitive problems (–> poor concentration/school performance)
- adenotonsillar hypertrophy (can –> OSA –> nocturnal hypoxaemia –>vaso-occlusive crisis/stroke)
- cardiac enlargement (from chronic anaemia)
- heart failure, renal dysfunction, leg ulcers, psychosocial problems, pigment gallstones (more bile produced)
How should acute vaso-occlusive crisis in sickle cell be managed?
- oral/IV analgesia
- good hydration (oral/IV)
- treat infection with abx
- give o2 if sats low
Give 2 indications for exchange transfusion in pts with sickle cell disease?
- priapism
- acute chest syndrome
- stroke
What medication increased HbF and is used for sickle cell children with recurrent crisis/acute chest syndrome to protect vs. further crises? What is the main side effect of this drug that should be monitored for?
- Hydroxycarbamide
- SE risk of white blood cell suppression
- what is the last stage of treatment available in sickle cell pts with stroke/no response to hydroxycarbamide?
- what are the big risks/difficulties with this?
- bone marrow transplant (90%cure rate)
- need an HLA-identical sibling to donate their bone marrow
- 5% risk of fatal transplant associated complications
What is the prognosis for children with sickle cell in terms of dying from a bacterial infection?
Long term life expectancy approximately..?
- 3% mortality in childhood
- 50% severe sickle cell pts die by 40yrs
What test is used to screen for sickle cell neonatally and prenatally?
- Guthrie test using the dried blood spots in the 1st week of life
- Pre-natally chorionic villus sampling
Sickle cell pts with HbSC have ~normal Hb level and have fewer painful crises (vs HbSS), what should be checked periodically in adolescence, due to a risk of ___ ___? they are also prone to develop ______ of the hips and shoulders.
- check eyes periodically, risk of proliferative retinopathy
- osteonecrosis
Sickle cell trait are carriers but is asymptomatic, why are they screened prior to a general anaesthetic?
-to make sure any additional effort to prevent hypoxia is made as sickling is theoretically poss if carriers are exposed to low o2 tension
Sickle cell trait are carriers but is asymptomatic, why are they screened prior to a general anaesthetic?
-to make sure any additional effort to prevent hypoxia is made as sickling is theoretically poss if carriers are exposed to low o2 tension
Hemopoiesis main site is the ____ whereas after birth the production is from the ___ ____
- liver
- bone marrow
What reason is behind why neonates are asymptomatic with sickle cell and signs only develop later in 1st year of life?
-higher HbF in first few months is protective
all Hb has an alpha-2 chain. What is the second chain in the following:
- HbF
- HbA
- HbA2
- HbF: gamma-2
- HbA: beta-2
- HbA2: delta-2
Neuroblastoma dx can be aided by the presence of what tumour marker in the urine?
Catecholamine excretion (VMA and HVA acids)
What tumour marker can be used to monitor treatment response in the context of germ cell and liver tumours
-alpha fetoprotein
Imatinib is a targeted therapy, it is a tyrosine kinase inhibitor that targets what? In context of what malignancies?
- targets the BCR-ABL fusion that causes the Philadelphia chromosome +:
- ALL
- and CML
Monoclonal abs can be used in cancer rx e.g. rituximab (anti-CD20) is used for l____ and
-anti-GD2 is used for treatment of high-risk n_____
- rituximab for lymphoma
- anti-GD2 for neuroblastoma
Fever + neutropenia in a immunosuppressed child should -> immediate admission and bs-abx. Cancer associated opportunistic infections include:
- what pneumonia in children w leukaemia?
- disseminated fungal infection caused by?
- and infection of central venous catheters by what type of organism?
- Pneumocystis Jiroveci
- Aspergillosis or candidiasis
- coagulase-negative staphylococcal infection
ALL is 80% of leukaemia in children, what is the next most common?
Acute non-lymphocytic leukaemia (ANLL) and AML
ALL peak age is 2-5yrs, presentation is variable. FBC is often abnormal how? And what ix is need to confirm dx and identify prognostic info?
- FBC: anaemia, thrombocytopenia, circulating leukemic blast cells
- BM exam
10% of children at the time of ALL diagnosis have what abnormality? Which is why all patients should have what screen at presentation?
- DIC
- clotting screen
Why is a LP and a CXR performed in the ix of ALL?
- LP: to identify disease in the CSF
- CXR: to identify a mediastinal mass characteristic of T-cell disease
Before starting ALL rx, anaemia may need correction, platelets given and infection treated. What is given when starting rx to protect renal function vs the effects of rapid cell lysis?
- hydration
- allopurinol or urate oxidase
Based on the general effects, BM, RES, CNS and testes infiltration suggest a sx each for ALLs presentation
- general: malaise, anorexia
- BM: bone pain, bruising, infection, pallor, lethargy
- RES: hepatosplenomegaly, lymphadenopathy
- CNS: headache, vomiting, nerve palsy
- Testes: testicular enlargement
Suggest 2 poor prognostic factors for ALL:
- age <1 or age >10yrs
- v high tumour load (high WCC 50+)
- cytogenic/molecular genetic abnormalities
- poor initial response to chemo
Neuroblastomas arise from neural ___ ____ in the adrenal ____ and sympathetic nervous system. It can spontaneously regress.
-neural crest tissue in adrenal medulla
Neuroblastoma is most common
- <5yrs
- benign = ganglioneuroma
How do most children (<5yrs) present with a neuroblastoma?
- an abdominal mass usually (but mass can lie anywhere along sympathetic chain neck-> pelvis)
- bone pain, BM suppression, weight loss, malaise are often presenting sx due to metastatic disease
Amplification of which oncogene predicts aggressive behaviour of neuroblastomas?
-MYCN
Management of Neuroblastoma in:
- pts w localised primaries w no mets:
- metastatic disease in older children:
- primaries: surgery alone
- mets: chemo, autologos stem cell rescue, surgery, radiotherapy
Wilms tumour aka ____blastoma. How do most present?
- nephroblastoma
- present with a large abdo mass often found incidentally in a well child
- presents with heamaturia
How is Wilm’s tumour investigated, what would you see?
- Ultrasound, CT/MRI
- intrinsic renal mass distorting the structure
How is Wilms tumour treated?
- initial chemo
- followed by delayed nephrectomy
Suggest 3 diagnostic clues that would point towards red cell aplasia as the cause of an anaemia:
- low reticulocyte count despite low Hb
- normal bilirubin
- negative Coombs test (DAT)
- absent red cell precursors on BM exam
Suggest 3 diagnostic clues that would point towards haemolysis as the cause of an anaemia:
- raised reticulocyte count & increased RBC precursors in BM
- unconjugated bilirubinaemia
- increased urinary urobilinogen
- abnormal red cells on blood film e.g. sphere, sickle, hypochromic…
- positive DAT Coombs test (if immune cause)
What is the inheritance of most Hereditary Spherocytosis
NB: 25% are sporadic new mutations
Autosomal Dominant
Mutations coding for what possible things leads to the clinical disease of Hereditary Spherocytosis
- coding for the RBC membrane proteins:
- Spectrin
- Ankyrin
- or Band 3
Mutations in the spectrin/ankyrin/band 3 RBC membranes in Hereditary Spherocytosis leads to destruction of cells where and how?
due to these mutations, RBC loses part of membrane as passes in spleen -> spheroidal shape
- mutations make the RBCs becomes less deformable
- so they are destroyed in the microvasculature of the spleen
Suggest 2 common sx of Hereditary Spherocytosis and 2 poss complications, one due to an infection, one due to increased excretion of a certain thing
- jaundice
- anaemia (usually mild but falls low during infections)
- splenomegaly
- aplastic crisis (caused by parovirus b19)
- gallstones (due to increased bilirubin excretion)
What is the main 2 oral medications used in Hereditary Spherocytosis management?
- oral folic acid
- life long daily oral penicillin prophylaxis
