Haematology/oncology

Question 1

Why do neonates have high Hb?

Answer 1

compensate for low o2 in fetus, because the lungs don’t work

it falls in the first few weeks due to reduced RBC production, more so in preterms, and is lowest at 8w

HbF is gradually replaced by HbA during infancy

Question 2

Ineffective erythropoiesis (normal rate but defective survival)

Answer 2

Usually normal reticulocytes + abnormal MCV (low in iron-def, high in folate def)

• iron def: common as need more intake to compensate for higher blood vol as they grow, breast milk low iron but half absorbed/cows milk more iron but less absorbed, may not have enough at weaning, may have malabsorption like coeliac. sx when <70 of tiring/feeding slowly/pallor of conjunctiva + MM. give oral iron until normal levels for 3m, should never need transfusion. If normal Hb but low ferritin: also give supplements as iron needed for brain development
• folate def
• chronic inflammation e.g. JIA
• CKD (low MCV)
• rare causes like lead poisoning

Question 3

Red cell aplasia (no red cells)

Answer 3

Low retics, normal bili, negative DAT, absence of red cell precursors on BM

• Parvovirus B19: only cause aplasia if they have haemolytic anaemia
• Diamond-Blackfan anaemia - congenital red cell aplasia, rare. need steroids, may need monthly transfusion
• Transient erythroblastopenia of childhood: always resolves in a few weeks
• Rare e.g. Fanconi anaemia, aplastic anaemia, leukaemia

Question 4

What are the causes of anaemia?

Answer 4

• impaired RBC production e.g. iron def, aplasia
• increased RBC destruction (haemolysis) e.g. haemoglobinopathies, immune destruction, red cell membrane disorders
• blood loss (uncommon in children)
• anaemia of the newborn

Question 5

Red cell membrane disorders

Answer 5

e.g. Hereditary spherocytosis: AD, spheroid cells so can’t squeeze through bv normally so get destroyed, may no sx or jaundice/anaemia/mild-moderate splenomegaly/gallstones
can get aplastic crisis if parvovirus B19 infection

Question 6

Red cell enzyme disorders

Answer 6

e.g. glucose 6 phosphate dehydrogenase deficiency

enzyme for protection against oxidative damage lost - susceptible to haemolysis - often induced by drugs like antimalarials/ciprofloxacin/nitrofurantoin/aspirin and also fava beans

x-linked so mostly males

cf: severe neonatal jaundice, acute haemolysis with fever/malaise/abdo pain/dark urine
m: usually is just to avoid the drugs that provoke it

Question 7

What are the haemoglobinopathies?

Answer 7

Thalassaemias & sickle cell disease

they cause haemolytic anaemia via reduced/absent production of HbA (thalassaemias) or abnormal Hb production (SCD)

Question 8

Beta thalassaemias

Answer 8

most severe is beta thal major as cant make HbA; intermedia is milder as small amounts made
Beta thal trait: heterozygotes, usually asymptomatic, supplement if needed

CF: transfusion-dependent from 3-6m if severe, jaundice, growth faltering, extra medullary haemopoeisis (hepatosplenomegaly, maxillary overgrowth, skull bossing)

M: monthly transfusions for major, iron chelation (repeat transfusion causes various issues like cirrhosis HF DM). BMT only cure, need HLA-identical sibling

Question 9

Alpha thalassaemias

Answer 9

CF depends on the number of functional alpha-globing chains!

Alpha thal major is when all 4 deleted - incompatible with life unless monthly transfusions (inc in utero)

HbH disease: 3 chain deletion, mild-moderate anaemia usually dont need transfusion

Alpha thal trait: 1/2 genes deleted, usually asymptomaitc/mild anaemia

Question 10

Sickle cell disease

Answer 10

AR - inheritance of HbS for the beta globin chain - polymerises within RBCs deforming their shape - trapped causing bone/organ ischaemia (exacerbated by low O2/dehydration/cold). HbSS when homozygous (most severe), HbSC (one HbS, one HbC, some features), carriers (one HbS, one normal). Need two abnormal Hb to have disease

CF: anaemia, jaundice, infection with encapsulated bacteria (due to hyposplenism, e.g. pneumococci, H influenzae, salmonella osteomyelitis), painful crises (pain in varying organs/limb + spine bones, if affects chest can cause severe hypoxia), AVN of femoral heads, acute anaemia e.g. parvovirus causing aplastic criss, priapism (need exchange transfusion), splenomegaly, long term comps

M:

• prophylaxis: penicillin, folic acid, reduce exposure to cold/dehydration/stress/excessive exercise, vaccination
• crises: analgesia, hydration, abx/oxygen if needed
• stroke/acute chest syndrome/priapism: exchange transfusion
• hydroxycarbamide: increases HbF production (higher O2 affinity
• may be cured by BMT but only poss if have a HLA-identical sibling

Prognosis: life expectancy 40-50ish

Screening: prenatal screening for carrier status in high risk area/pts, neonatal heel prick test

Question 11

Immune causes of haemolysis

Answer 11

• haemolytic disease of the newborn

* autoimmune haemolytic anaemia (uncommon in children)

Question 12

How might blood loss in children lead to anaemia?

Answer 12

• chronic GI losses e.g. Meckel diverticulum

* inherited disorders e.g. vWD

Question 13

Anaemia of the newborn

Answer 13

• reduced RBC production e.g. Diamond-Blackfan anaemia, congenital parvovirus B19 infection. low Hb, normal bili
• increased destruction: high retics + unconjugated bili. May be immune like HDN, hereditary spherocytosis, abnormal Hb like alpha thal major
• blood loss: v low Hb, high retics, normal bili. Veto-Maternal haemorrhage, TTTS, placental abruption
• anaemia of prematurity: multifactorial inc inadequate EPO production, reduced RBC lifespan, frequent blood samples whilst in hospital, iron + folate def after 2-3m (born with enough but premature use stores up faster)

Question 14

Aplastic anaemia

Answer 14

Reduction/absence of all three major lines –> anaemia, infection + thrombocytopenia

May be acquired from viruses/drugs/toxins/idiopathic, or inherited like Fanconi anaemia (AR, often congenital anomalies too, need BMT as risk of acute leukaemia + BM failure)

Question 15

What investigations would you do for a possible bleeding disorder?

Answer 15

FBC + blood film
PT time and APTT time: measure activity of various clotting factors, if prolonged may be a deficiency or something inhibiting the factors
Thrombin time: for deficiency or dysfunction of fibrinogen
D-dimers: fibrin degradation products
Biochemistry like U+E, LFT
Platelets: acquired bleeding disorders

Age-specific ranges

Question 16

What are the acquired disorders of coagulation?

Answer 16

Haemorrhagic disease of the newborn, liver disease, ITP or DIC

Question 17

Vitamin K deficiency

Answer 17

Vit K needed for factors 2, 7, 9 + 10 + protein C+S (anticoagulants)

Can be due to poor intake, malabsorption, vitamin K antagonists (RF if breast fed + mother on AEDs)

Give IM vitamin K to all newborns, if mother on AED mother needs oral prophylaxis from 36w

Haemorrhagic disease of newborn: up to 8w, usually bruising/prolonged bleeding from umbilical stump/haematemesis/melaena, can cause ICH

Question 18

CF of thrombocytopenia

Answer 18

Risk of severe bleed if plt <20, or during operations if <50; 50-150 is mild TP

CF: bruising, petechiae, purpura, mucosal bleeding, major GI/haematuria/intracranial bleeding

Question 19

ITP

Answer 19

Commonest cause of thrombocytopenia in children - plt destruction by anti-platelet IgG autoantibodies

CF: 1-2w post viral illness with petechiae/purpura/superficial bruising, may get mucosal bleeding but severe bleeding rare (even tho plt often below 10)

Diagnosis: of exclusion. In young kids consider congenital, if suggestive of leukaemia/aplastic anaemia do a BM, do BM if going to give steroids (as steroids may mask ALL diagnosis). Don’t do BM if no intention to treat

M: 80% resolve in 6-8w alone. If severe bleeding/persisting, can try oral pred/IV anti-D/IV IgG/plt transfusion in life threatening (as only works for a few hours anyway)

Chronic ITP: when remains low after 6m, usually supportive treatment. If affects QoL can try rituximab, or splenectomy; screen for SLE

Question 20

DIC

Answer 20

Coag activated - fibrin deposited in microvasculature + clotting factors consumed [there is a chronic type too]

Causes: sepsis, shock, extensive tissue damage from trauma/burns

CF: bruising, purpura, haemorrhage

Ix: low plt, prolonged PT+APTT, low fibrinogen, high D-dimers, microangiopathic haemolytic anaemia, low protein C+S+antithrombin

M: treat cause e.g. FFP + cryo + plts

Question 21

Haemophilia

Answer 21

X-linked recessive (usually boys), type A (factor 8 def) and type B (factor 9 def, rarer), 50% random mutation so don’t have a FH

Forms: severe (spontaneous joint/muscle bleeds), moderate (bleed after minor trauma) or mild (bleed from surgery)

Joint bleeding can cause severe arthritis

often present when start to crawl/walk, or in neonatal period with ICH/prolonged bleeding from heel stick sites

M: recombinant factors for the deficiency (IV for acute bleeding), in haemophilia A often need injection every 48h/haemophilia B twice per week; for milder cases may just need on demand treatment where inject the clotting factor when there is bleeding / in haemophilia A can also use desmopressin (can stimulate natural production of factor 8 + vWF)

Comps of treatment: local reactions, vascular access issues, antibodies made to factors, transfusion-associated infection

Question 22

Von Willebrand disease

Answer 22

Deficiency of vWF - defective platelet plug formation plus factor 8 deficiency (because vWF is a carrier protein)

usually AD + mild, may have bruising/excessive bleeding from surgery/mucosal bleeds

m: depends on type

Question 23

Acute lymphoblastic leukaemia CF

Answer 23

Peak 2-5y, some a/w Philadelphia chromosome (though this is more in CML, but if identify can treat with imantinib)

Usually insidious onset over weeks but can be rapid

• general: malaise, anorexia
• BM infiltration: pallor/lethargy (anaemia), infection (neutropenia), bruising/petechiae/epistaxis (TP), bone pain (infiltration)
• reticulo-endothelial involvement: hepatosplenomegaly (abode pain), lymphadenopathy, superior mediastinal obstructing (uncommon)
• other organ spread (rare @ diagnosis): CNS (headache, vomiting, nerve palsies), testicular enlargement

Ix: low Hb, TP, circulating leukaemia blast cells; BM to confirm + identify immunological/cytogenic characteristics, clotting-~10% have DIC at diagnosis, LP for CSF disease (at same time as BM, both under GA), CXR (mediastinal masses seen in T cell disease)

Question 24

Acute lymphoblastic leukaemia: lower prognostic factors

Answer 24

Aged <1 or >10y
High WCC >50 (indicates high tumour load)
Cytogenetic abnormalities e.g. MLL rearrangement
Persisting leukaemic blasts in the BM after initial chemo
Minimal residual disease detectable after induction
Male (? is it cos of testicular involvement)

Question 25

Acute lymphoblastic leukaemia management

Answer 25

• General: correct anaemia/DIC, treat infection, hydration, allopurinol/rasburicase for TLS prophylaxis
• Induction: to eradicate leukaemic blasts + restorate normal BM function. Includes steroids, also intrathecal chemotherapy (usually methotrexate; never give vincristine/other vinca alkaloids IT!) [prophylaxis or higher dose if CNS disease]
• Intensification: intensive chemo to consolidate remission
• Maintenance: modest intensity chemo for 2-3y
• BMT: may be given after a relapse

Question 26

Thrombosis in children

Answer 26

Uncommon but should not miss, usually due to a hyper coagulable state, can cause stroke if in cerebral vessels

Caused by inherited thrombophilias such as factor V Leiden (makes factor V resistant to degradation) or acquired things like polycythaemia in CHD or malignancy

Question 27

Lymphoma

Answer 27

3rd commonest cancer in children

NHL: more in children. T cell types may also present as ALL, may have mediastinal mass with BM infiltration, may have SVCO; or B cell NHL which is more localised LN disease (pain, masses, intussusception)

HL: more adolescents, Painless LN mostly of neck, often other months, B symptoms uncommon

Burkitt lymphoma: B cell NHL, linked to EBV. Groups are endemic in Africa, sporadic and immunodeficiency

Question 28

Neuroblastoma

Answer 28

<5y, arise from neural crest tissue in adrenal medulla + SNS

sometimes spontaneously regress in infants, even if metastatic

a spectrum from benign to highly malignant

Cf: abdo mass, bone pain, BM suppression, malaise, WL, hepatomegaly, limp

Ix: high catecholamines in urine

M: if not regresses/older child chemo, surgery, radio. metastatic has 40% cure rate

Question 29

Wilm’s tumour (nephroblastoma)

Answer 29

<5y, v rare >10y. originates from embryonic renal tissue

CF: large abdo mass + haematuria are main things; may get abdo pain/anorexia/anaemia

M: nephrectomy, chemo, radiotherapy, prognosis quite good unless relapse

Question 30

What supportive care is needed for children with cancer?

Answer 30

• social factors esp teenagers (they also have worse prognosis cos of their tumour behaviour)
• fertility preservation
• venous access
• psychosocial impact on whole fam, discuss implications of diagnosis
• education
• neuropsychological sx from cranial irradiation/surgery
• specific organ dysfunction
• growth/endocrine monitoring: GH def from pituitary radiation, bone growth retardation at sites of radiation

Question 31

Features of haemolysis

Answer 31

May be intravascular or extravascular (in liver/spleen)

CF: anaemia, hepatosplenomegaly, increased uncongjugated bili, excess urinary urobilinogen, raised retics, abnormal appearance of red cells, increased RBC precursors in BM

Positive DAT if immune cause

Question 32

Long term complications of sickle cell

Answer 32

Short stature, delayed puberty, stroke, neuro damage, adenotonsillar hypertrophy, cardiac enlargement due to chronic anaemia, HF, renal dysfunction, pigment gallstones, leg ulcers in adults, psychological/behavioural/educational difficulties

Question 33

Sickle cell mutation

Answer 33

Point mutation where glutamic acid is substituted by valine

Autosomal recessive

Question 34

Haemolytic disease of the newborn

Answer 34

Antibodies against blood group antigens (most importantly anti-D of rhesus group, anti-A/anti-B of ABO group, and anti-Kell)

mother negative for the antigen + baby positive

mother makes antibodies against baby’s blood group - crosses placenta - causes HA

positive DAT

Question 35

Causes of purpura

Answer 35

• Increased plt destruction/consumption (TP): immune e.g. ITP/SLE, non-immune e.g. HUS/TTP/DIC/congenital heart disease
• Impaired plt production (TP): congenital e.g. Fanconi anaemia, acquired e.g. marrow infiltration/drugs
• Plt dysfunction (normal plt count): rare congenital disorders, uraemia, cardiopulmonary bypass
• Vascular disorders (normal plt): congenital e.g. Marfan/HHT, severe infections, vasculitis like HSP/SLE

Question 36

Brain tumours

Answer 36

2nd commonest cancers in kids after leukaemia, usually primary e.g. astrocytoma (varies from benign to v malignant), medulloblastoma, craniopharyngioma

CF: vomiting, balance/coordination problems, behaviour change, eye movement abnormal, non-febrile seizures

• child/adolescent: recurrent headache, blurred/double vision, lethargy, delayed/arrested puberty, slow growth
• infants: developmental delay/regression, HC increase, separation of sutures, lethargy

M: surgery to treat hydrocephalus, tissue diagnosis + primary resection

Question 37

Bone tumours

Answer 37

Uncommon pre-puberty, M>F

Osteosarcoma - commonest

Ewing sarcoma - more in younger

Limbs commonest site causing persistent localised bone pain so have low threshold for XR

Question 38

Retinoblastoma

Answer 38

All bilateral hereditary and 15% of u/l also hereditary

CF: white pupillary reflex, squint

M: aim is to cure + preserve vision, may need enucleation

Question 39

Soft tissue sarcomas

Answer 39

E.g. rhabdomyosarcoma

Mostly in H+N so get things like exophthalmos, bloody nasal discharge, nasal obtruction