Haematology/oncology Flashcards
Anaemia, bleeding disorders, cancers
Why do neonates have high Hb?
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
Ineffective erythropoiesis (normal rate but defective survival)
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
Red cell aplasia (no red cells)
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
What are the causes of anaemia?
- 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
Red cell membrane disorders
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
Red cell enzyme disorders
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
What are the haemoglobinopathies?
Thalassaemias & sickle cell disease
they cause haemolytic anaemia via reduced/absent production of HbA (thalassaemias) or abnormal Hb production (SCD)
Beta thalassaemias
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
Alpha thalassaemias
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
Sickle cell disease
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
Immune causes of haemolysis
- haemolytic disease of the newborn
* autoimmune haemolytic anaemia (uncommon in children)
How might blood loss in children lead to anaemia?
- chronic GI losses e.g. Meckel diverticulum
* inherited disorders e.g. vWD
Anaemia of the newborn
- 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)
Aplastic anaemia
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)
What investigations would you do for a possible bleeding disorder?
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
What are the acquired disorders of coagulation?
Haemorrhagic disease of the newborn, liver disease, ITP or DIC
Vitamin K deficiency
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
CF of thrombocytopenia
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
ITP
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
DIC
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
Haemophilia
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
Von Willebrand disease
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
Acute lymphoblastic leukaemia CF
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)
Acute lymphoblastic leukaemia: lower prognostic factors
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)
Acute lymphoblastic leukaemia management
- 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
Thrombosis in children
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
Lymphoma
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
Neuroblastoma
<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
Wilm’s tumour (nephroblastoma)
<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
What supportive care is needed for children with cancer?
- 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
Features of haemolysis
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
Long term complications of sickle cell
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
Sickle cell mutation
Point mutation where glutamic acid is substituted by valine
Autosomal recessive
Haemolytic disease of the newborn
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
Causes of purpura
- 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
Brain tumours
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
Bone tumours
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
Retinoblastoma
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
Soft tissue sarcomas
E.g. rhabdomyosarcoma
Mostly in H+N so get things like exophthalmos, bloody nasal discharge, nasal obtruction
