Paediatric Haematology Flashcards
What is iron deficiency anaemia?
mc anaemia
needed to make hb in rbc so def = reduction in rbc/hb
epidemiology of iron def anaemia
pre-school age children
causes of iron def anaemia
excessive blood loss: pre-menopause, gi bleed(men colon cancer) post menopause
inadequate diet: eat meat, dark leafy veg.
poor intestine absorption: coeliac
increased iron requirement: periods of rapid growth. pregnancy. increase in plasma vol in pregnancy causing iron def through dilution.
features of iron def anaemia
fatigue
sob on exertion
palpitations
pallor
nail changes: koilonychia spoon shaped
hairloss
atrophic glossitis
post-cricoid webs
angular stomatits
ix for iron def anaemia
history- look for cause
fbc - hypochromic microcytic anaemia
serum ferritin: low - correlates with iron stores. ferritin can be raised in inflammation.
total iron binding capacity/transferrin - high. - high tibc= low iron stores. transferrin sats will be low.
blood film: anisopoikilocytosis - rbc diff size and shapes, target cells (pencil) poikilocytes
endoscopy: rule out malignancy. - men and post menopause women with unexplained iron def. post men with hb under or 10 or men 11 or less refer within 2 weeks to gi.
how would you manage iron def anaemia?
identify cause
oral ferrous sulfate: 3 months to replenish.
iron rich diet: dark leafy veg, meat, iron fortified bread
blood transfusion - rare
common side effects of iron supps
nausea
abdo pain
constipation
diarhoea
hb produced where
requires what
bm
iron
drugs that can interfere with iron absorption
ppi - lansoprazole omeprazole
normal ranges for irons
serum ferritin - 12-200 ug/l
serum iron 14-31 umol/L
tibc - 54-75 umol/l
ranges of iron - what 2 things can increase these values
iron supps
acute liver damage - iron stored there
types of microcytic anaemia
iron def
thalassaemia
congenital sideroblastic anaemia
anaemia of chronic disease- mc normocytic, normochromic picture
lead poisoning
pt with normal hb level with microcytosis.
not at risk of thalasemia, what is it?
poss polycythaemia rubra vera which can cause iron def anaemia secondary to bleeding
alpha thalassaemia
tell me about it
depending on amount of alpha globulin alleles affected
mx
due to def of alpha chains in hb
2 seperate alpha globulin genes located on each chr 16
severity depending on no. of alpha globulin alleles affected:
if 1/2 - blood picture is hypochromic and microcytic - normal hb level
if 3: hypochromic microcytic anemia with splenomegaly. Hb H disease
if all 4 : homozygote - death in utero (hydrops fetalis, barts hydrops) - alpha major
monitor
blood transfusion
splenectomy
bm transplant - cure
beta thalassemia major - tell me about it
absence of beta globulin chains
chr 11 - either abnormal copies that retain some function or deletion with no function in the beta-globin.
1st yr of life with failure to thrive and hepatosplenomegaly
microcytic anaemia
hba2 and hbf raised
hbA absent
mx: repeated transfusion
leads to iron overload = organ failure
iron chelation therapy important: desferrioxamine
beta-thalassaemia trait - tell me about it
group of genetic disorders characterised by reduced production rate of either alpha or beta chains.
autosomal recessive
mild hypochrommic microcytic anaemia.
asx
microcytosis - disproportionate to anemia
hbA2 raised over 3.5%
thalassemia are what genetic
autosomal recessive both
whats up with the rbc of thalassaemia pts?
more fragile break down easily
haemolytic anaemia
spleen acts like a sieve, filters blood and removes older cells.
collected all destoryed rbc = splenomegaly
features of thalassaemia
microcytic anaemia - low mean corpuscular volume
fatigue
pallor
jaundice
gallstones
splenomegaly
poor growth and development
ix for thalassaemia
microcytic anaemia - low mean cell vol - fbc
raised ferritin = iron overload
hb electrophoresis - diagnose globin abnormalities.
dna testing: genetic abnormality .
do for all pregnant women.
why might iron overload happen in thalassaemia?
increased iron absorption in gi tract.
blood transfusion
iron overload in thalassaemia sx and comps of ?
liver cirrhoiss
hypogonadism
hypothyroidism
hf
dm
osteoporosis
mx of iron overload
serum ferritin- monitor
limit transfusions
iron chelation
3 types of beta thalassaemia
minor - trait - carrier - 1 abnormal 1 normal. mild microcytic anaemia - just monitor
intermedia - 2 abnormal copies. 2 defective or 1 defection and 1 deletion. more significant microcytic anaemia. occasional blood transfusion. poss iron chelation prevent iron overload
major - homozygous for deletion. no functioningbeta-globin. more severe. severe anaemia./ failure to thrive in early chilhood.
bm under stain to produce extra rbc. - expands- increase risk of fractures = pts appearance change.
bone changes in thalassaemia major
frontal bossing - prominent forehead
enlarged maxilla - prominent cheekbones
depressed nasal bridge - flat nose
protruding upper teeth
What is sideroblastic anaemia?
rbc fail to complete form haem - whose biosynthesis happens in mitochondria.
leads to deposits of iron in mitochondria - form ring around nucleus called sideroblast.
can be congenital or acquired.
congenital cause of sideroblastic anaemia
delta-aminolevulinate synthase 2 deficiency
acquired causes of sideroblastic anaemia
myelodysplasia
alcohol
lead
anti-tb meds
ix of siderblastic anaemia
fbc - hypochromic microcytic anaemia - more in congenital
iron studies: high ferritin, high iron, high transferrin saturation
blood film: basophilic stippling of rbc
bm: prussian blue staining - ringed sideroblasts
how would you manage sideroblastic anaemia?
support
tx underlying
pyridoxine - might help
what is pyridoxine
causes
consquences
vit b6
water soluble vit of b complex group.
converted to pyridoxal phosphate - cofactor for many reactions including transamination, deamination and decarboxylation.
causes: isoniazid therapy
consequences of vit b6 def:
-peripheral neuropathy
- sideroblastic anaemia
is jaundice in first 24 hrs always pathological?
causes?
yes
rhesus haemolytic disease
ABO haemolytic disease
hereditary spherocytosis
glucose -6 - phosphodehydrogenase
jaundice in neonate 2-14 days how common
causes
upto 40% - common
physiological
due to combo of factors:
- more rbc,
more fragile rbc and less developed liver function
more in breastfed babies
jaundice after 14 days - prolonged
causes why?
21 days if premature
do jaundice screen:
tft
fbc blood film
urine for mc s and reducing sugars
direct antiglobulin test - coombs test
u and e
conjugated and unconjugated billirubin : raised conjugated tells you biliary atresia - urgent surgical intervention
causes of prolonged jaundice
biliary atresia
hypothyroidism
galactosaemia
uti
breast milk jaundice: mc in breastfed. high conc of beta glucoronidase - increase in intestinal absorption of unconjugated billirubin
premature: immature liver function. increase risk of kernicterus (brain damage due to high billirubin)
congenital infections: cmv, toxoplasmosis
before birth how is rbc break down released
excreted via placenta.
so normal rise in billirubin shortly after birth, mild yellowing of skin and sclera for 2-7 days.
resolves usually by 10 days
what is haemolytic disease of the newborn?
cause of haemolysis - rbc breaking down
and jaundice in neonate.
caused by incompatibility between rhesus antigens on surface of rbc of mother and fetus.
rhesus antigens on rbc vary between individuals.
different to ABO system.
tell me about the rhesus group and haemolytic disease of newborn?
many different types of antigens that can be present or not in rhesus group but most important is rhesus D antigen.
is women rhesus D negative and becomes pregnant;l consider if child could be positive - likely pregnancy the blood from baby will go into her bloodsteam. then babies rbc will display negative. mothers immune system will recognise with resus D antigen as foreign produce antibodies and the mother sensistsed to reshus D antigens.
usually doesnt cause problems in first pregnancy - unless early during antepartum haemorrhage.
susequent: mother anti-d antibodies can cross placenta. if fetus is position - antibodies attach to rbc of fetus. immune system of fetus to attack own rbc. = haemolysis, anaemia and high billirubin.
test for direct antiglolubin testing for haemolysis
direct coombs
how to manage neonatal jaundice?
plot and monitor on tx threshold charts - total billirubin. - specific for gestational age.
age of baby -x
total billirubin - y
phototherapy- adequate.
extremely high: exchange transfuson - remove blood from neonate and replace with donor blood
what is kernicterus
presentation
damage can cause?
brain damage due to excess billirubin
can cross blood brain barrier.
direct damage to cns
less responsive
floppy
drowsy baby
poor feeding.
cerebral palsy
LD
deafness
What is fanconi anaemia?
features
autosomal recessive.
featureS:
haematological: aplastic anaemia - increased risk of aml
neurological
skeletal abnormalities: short stature
thumb/radius abnormalities
cafe au lait spots
what is fanconi syndrome?
generalised reabsorptive disroder or renal tubular transport in proximal convoluted tubule resulting in:
type 2 (proximal) renal tubular acidosis
polyuria
aminoaciduria
glycosuria
phosphaturia
osteomalacia
causes of fanconi syndrome?
cystinosis - mc children
sjogrens syndrome
multiple myeloma
nephrotic syndrome
wilsons disease
What is sickle cell anaemia?
genetic component?
protective against.
autosomal recessive
synthesis of abnormal hb chain termed HbS.
mc : african heterozygous condition offers some protection against malaria.
such ppl only sx if severely hypoxic
ix for sickle cell anaemia
haemoglobin electrophoresis
pathophysiology of sickle cell anaemia
hb - normal : HbAA
sickle cell trait: HbAS
homozygous sickle cell diseasE: HbSS: some pts inherit 1 HbS and another abnormal hb (HbC) = milder form of sickle cell disease (HbSC)
polar amino acid glutamate substituted by non polar valine in each of 2 beta chains(codon 6) - decreases water solubility of deoxy-Hb
in deoxygenated state HbS molecules polymerise and cause RBC to sickle
sickle cells fragile and haemolyse : block small bv and cause infarction
deoxygenated state HbS molecule polymerise and cause rbc to sickle at what po2?
HbAS - po2 2.5-4kpa
HbSS - po2 5-6 kpa
how would you manage sickle cell anaemia?
longer term
vaccine
crisis mix:
analgesia: opiates
rehydrate
oxygen
consider abx if infectio
blood transfusion
exchange transfusion: if neuro comps
longer term x:
hydroxyurea - increase HbD levels - prophylactic mx of sickle cell anaemia to prevent painful eps
sickle cell pts - pneumoccocal polysaccharide vaccine every 5 yrs
avoid triggers - stay hydrated
vaccination
abx prophylaxis - penicillin v - phenoxymethyl
hydroxycarbamide - hbf stimulator
crizanlizumab
blood transfusion
m transplant
indications for blood transfusion in sickle cell crisis?
severe or sx anaemia, pregnancy, pre-operative
dont rapidly reduce percentage of Hb S containing cells
indications for exchange transfusion in sickle cell crisis
acute vaso-occlusive crisis - stroke, acs, multiorgan failure, splenic sequestration crisis
rapidly reduce percentage of HbS containing cells
types of sickle cell crisis
thrombotic, “vaso-occlusive”, “painful crises”
acs
anaemia: aplastic, sequestration
infection
thrombotic crisis - sickle cell crisis - tell me about it
precipitated by
diagnosis
infarcts occur where
painful crisis/vaso-occlusive
precipated by infection dehydration, deoxygenation (high altitude)
clinical diagnosis
infarcts occur in various organs including bones (avascular necrosis of hip, hand-food syndrome in children lungs spleen and brain)
acs - sickle cells crisis - tell me about it
sx
mx
vaso-occlusion within pulmonary microvasculature : infarction in lung parenchyma
dyspnoea
chest pain
pulmonary infiltrates on cxr, low po2
mx:
pain relief
resp support: ox therapy
abx: infection may precipitate: hard to distinguish from pneumonia
tranfusion: improves oxygenation
mc cause of death after childhood
aplastic crisis - sickle cell crisis
caused by
patho
caused by infection with parovirus
sudden fall in hb
bm suppression causes reduced reticulocyte count
sequestration crisis - sickle cell crisis
tell me about it
associated with?
sickling within organs like spleen or lungs cause pooling of blood with worsening of anaemia
associated with increased reticulocyte count.
pathophysiology of sickle cell anaemia
at 32-36 weeks gestation hbF production decreases and HbA increases.
gradual transition
by 6 months very little hbf produced.
pts with sickle cell has hbs. - sickle cellshaped.
complications of sickle cell anaemia
anaemia
increased risk of infection
ckd
sickle cell crisis
acs
stroke
avascular necrosis: large joint like the hip
pulmonary htn
gallstones
priapism - painful and persistent penile erections
triggers of sickle cells crisis
dehydration
infection
stress
cold weather
how does crizanlizumab work?
monoclonal antibody target p selectin.
p selectin - adhesion molecule on endothelial cells on inside walls of blood vessels and platelets.
prevents rbc from sticking to bv wall and reduces frequency of vaso-occlusive crisis
sickle cell trait protective against
malaria
if 1 copy - trait - reduce severity of malaria
selective advantage
screening for sickle cell
newborn blood spot - 5 days of age.
pregnant women at high risk of carrier - offered testing
tell me about g6pd
rbc enzyme defect.
mediterranean and africa
xlinked recessive.
many drugs precipitate a crisis aswell as infections and broad(fava) beans
features of g6pd
neonatal jaundice
intravascular haemolysis
gallstones common
splenomegaly poss
heinz bodies on blood film: bite and blister cells poss
how would you diagnose g6pd
g6pd enzyme assay
check levels around 3 months after acute ep of haemolysis, rbc with most severely reduced g6pd activity will have haemolysed = reduced g6pd activity = not be measured in assay = false negative results
what drugs can cause haemolysis
anti-malarials: primaquine
ciprofloxacin
sulph-group drugs: sulphonamides,sulphasalazine, sulfonylureas
some drugs safe for not causing g6pd
penicillins
cephalosporins
macrolides
tetracyclines
trimethoprim
g6pd - affect which gender
xlinked recessive
only men
what is hereditary spherocytosis?
mc hereditary haemolytic anaemia - northern europe
autosomal dominant defect of rbc cytoskeleton
normal biconcave disc shape replaced by sphere shaped rbc
rbc survival reduced as destroyed by spleen
presentation of hereditary spherocytosis
failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parovirus infection
degree of haemolysis variable
MCHC elevated
how would you diagnose hereditary spherocytosis?
ema binding test
cyrohaemolysis
if atypuical: electrophoresis analysis of erythrocyte membranes
mx of hereditary spherocytosis
acute haemolytic crisis: tx supportive , transfusion if needed
longer term: folate replacement
splenectomy
if gallstone present: remove gallblader: cholecystectomy
pt with spherocytosis present with anaemia
identify causative infectious agent.
parovirus cause
what is zieve syndrome?
rare clinical syndrome of coombs-negative haemolysis , cholestatic jaundice, transient hyperlipidemia associated with heavy alcohol use- after binge
stop alcohol - itll get better
hereditary causes of haemolytic anaemia
membrane: hereditary spherocytosis/elliptocytosis
metbaolism: g6pd
haemoglobinopathies: sickle cell, thalassaemia
acquired haemolytic anaemia split into acquired immune causes?
coombs-positive
autoimmune: warm/cold antibody type
alloimmune: transfusion reaction, haemolytic disease newborn
drug: methyldopa, penicillin
acquired haemolytic anaemia split into acquired non immune cause
coombs-negative
microangiopathic haemolytic anaemia: ttp/hus, dic, malignancy, pre-eclampsia
prosthetic heart valves
infections: malaria
drug: dapsone
zieve syndrome
what is autoimmune haemolytic anaemia?
2 types
causes
divide into warm and cold types.
depends of temp that antibodies best cause haemolysis.
idiopathic
secondary to lymphoproliferative disorder
infection
drugs
ix for autoimmune haemolytic anaemia
general features of haemolytic anaemia: anaemia, reticulocytosis, low haptoglobin, raised lactate dehydrogenase (LDH) and indirect bilirubin
blood film: spherocytes and reticulocytes
specific for autoimmune:
positive direct antiglobulin test - coombs test
causes of warm autoimmune haemolytic anaemia
mc type of autoimmune haemolutic anaemia
idiopathic
autoimmune diseasE: sle
neoplasia: lymphoma, cll
drugs: methyldopa
mx of warm autoimmune haemolytic anaemia
tx of underlying disorder
steroids +/- rituximab - 1st line
cold autoimmune haemolytic anemia what ig is it?
what temp
mediated by what
sx ?
igm - causes haemolysis best at 4 degrees.
mediated by complement and mc intravascular.
sx of raynauds and acrocyanosis.
pts respond less well to steroids
causes of cold autoimmune haemolytic anaemia
neoplasia: lymphoma
infections: mycoplasma, ebv
warm autoimmune haemolytci - what ig - (antibody~)
what temp best
where?
igg
body temp
haemolysis in extravascular sites eg spleen
mx of autoimmune haemolytic anaemia
blood transfusions
prednisolone
rituximab - monoclonal antibody against b cells
splenectomy
what is haemophilia?
a
b
lack of what factors
x linked recessive disorder of coagulation. (bleeding disorder)
30% have no fhx of it.
A - due to def of factor VIII whilst in B (christmas disease) lack fo factor IX
10-15% pts with haem a get antibodies to factor VIII tx
features of haemophilia
haemoarthroses
haematomas
prolonged bleeding after surgery or trauma
blood tests for haemophilia
prolonged aptt
bleeding time, thrombin time, prothrombin time normal
how to diagnose haemophilia
bleeding scores
coagulation factor assays
genetic testing
how would you manage haemophilia
comp of tx
affected clotting factors (VIII and ix) - iv infusion - either reguarly or in response to bleeding.
comp : formation of antibodies (inhibitors) against treamtent,so they become ineffective tx
areas of bleeding in haemophilia
oral mucosa
nosebleeds - epistaxis
gi tract
urinary tract - haematuria
intracranial haemorrhage
surgical wounds
when does haemophilia present?
how can it present?
neonates or early childhood.
intracranial haemorrhage
haematoma
cord bleeding in neonates
explain x linked recessive for haemophilias in terms of affecting men and women
men only have 1 x - require 1 abnormal copy to have disease.
females have 2 x - when 1 copy affected - asx carriers.
haem a and b - affects males more. if female affected they need to have affected father and mother who is either carrier or affected
Explain the iron deficiency testing
the knowledge behind them
tibc
ferritin
