Paeds - Haematology Flashcards
what makes up adult haemoglobin?
4 protein sub-units made of two pairs of sub-units
2 alpha and 2 beta sub-units
what makes up foetal haemoglobin?
4 protein sub-units made up of 2 alpha and 2 gamma sub-units
why does foetal Hb need to be different?
adult Hb picks up O2 in the lungs
foetal Hb picks up O2 in the placenta and has to steal it from mothers Hb
which has a greater affinity for O2, adult or foetal Hb?
foetal (o2 binds easier and is more reluctant to let go basically)
adult vs foetal Hb on oxygen dissociation curve?
foetal has a steeper upward slope
(ie adult Hb needs a higher partial pressure of O2 to “fill up” with oxygen wherease foetal Hb will “fill up” with O2 at lower concentrations of O2)
how does Hb change during development?
production of foetal Hb decreases from 32-36 weeks gestation
during this time, production of adult Hb increases
over time there is a gradual transition from HbF to HbA
how does Hb change after birth?
at time of birth, total Hb is 50% foetal and 50% adult
by 6 months old very little HbF is produced and eventually all RBCs will contain only HbA
how is foetal HB affected in sickle cell disease?
sickle cell disease is a genetic abnormality in area coding for beta subunit of Hb
foetal Hb doesnt have a beta subunit so there is no sickling of RBCs (until adult Hb is the prominent type of Hb)
what can be used to increase production of HbF in patients with sickle cell anaemia?
hydroxycarbamide
has protective effect against sickle cell crises and acute chest syndrome
what is sickle cell anaemia?
genetic condition causing sickle (crescent) shaped RBCs which makes them more fragile and easily destroyed leading to a haemolytic anaemia
what causes sickle cell anaemia?
autosomal recessive condition where there is an abnormal gene for beta globin on chromosome 11
patients with sickle cell have an abnormal variant of Hb called HbS which causes RBCs to be abnormal sickle shape
sickle cell trait vs disease?
one cope of abnormal gene for beta globin = sickle cell trait (usually asymptomatic)
two copies = sickle cell disease (symptomatic)
how is sickle cell disease related to malaria?
more common in patients from areas traditionally affected by malaria
having one cope of the gene (sickle cell trait) reduces severity of malaria
how is sickle cell diagnosed?
pregnant women at risk of being carriers of the gene are offered testing in pregnancy
sickle cell disease is also tested for on the newborn screening heel prick test at 5 days old
possible complications of sickle cell disease?
anaemia increased risk of infection stroke avascular necrosis of large joints (eg hip) pulmonary hypertension painful and persistent penile erection (priapism) chronic kidney disease sickle cell crises acute chest syndrome
general management of sickle cell disease?
avoid dehydration and other triggers of crises
ensure vaccines up to date
antibiotic prophylaxis (usually with penicillin V)
hydroxycarbamide can stimulate HbF production
blood transfusion for severe anaemia
bone marrow transplant can cure
what is a sickle cell crisis?
umbrella term for a spectrum of acute crises related to the condition
range from mild to life threatening
can occur spontaneously or triggered by stresses
what can trigger sickle cell crisis?
infection
dehydration
cold
significant life events
how is sickle cell crisis managed?
supportively
- treat any infection
- keep warm
- keep hydrated (may need IV fluids)
- simple analgesia
- treat priapism with penile aspiration
4 types of sickle cell crisis?
vaso-occlusive crisis (AKA painful crisis)
splenic sequestration crisis
aplastic crisis
acute chest syndrome
what is a painful crisis?
causes by sickle shaped RBCs clogging capillaries and causing distal ischaemia
symptoms of painful crisis?
pain
fever
symptoms of triggering infection (if present)
can cause priapism in men by trapping blood in penis
what can cause painful crisis?
dehydration
infection
high haematocrit
what is splenic sequestration crisis?
where RBCs block blood flow within the spleen
causes acutely enlarged and painful spleen
pooling of blood in the spleen can lead to severe anaemia and circulatory collapse
how is splenic sequestration crisis managed?
emergency
supportive management
blood transfusions and fluid resuscitations used to treat anaemia and shock
splenectomy used as preventative measure in cases of recurrent crisis
what is an aplastic crisis?
where there is temporary loss of the creation of new blood cells
leads to significant anaemia
what usually triggers aplastic crisis?
parovirus B19
how is aplastic crisis managed?
supportive
blood transfusions if needed
resolves spontaneously within a week
how is acute chest syndrome diagnosed?
diagnosis requires presence of fever or resp symptoms + new infiltrates seen on CXR
what can cause acute chest syndrome?
infection (eg pneumonia or bronchiolitis)
non-infective causes (eg pulmonary vaso-occlusion or fat embolism)
how is acute chest syndrome managed?
medical emergency
prompt supportive management and treatment of underlying cause
- antibiotics or antivirals for infection
- blood transfusions for anaemia
- incentive spirometry to encourage effective deep breathing
- artificial ventilation if needed
what is ITP?
condition where there is idiopathic (spontaneous) thrombocytopaenia causing a non-blanching purpuric rash
what causes ITP?
type 2 hypersensitivity reaction
caused by production of antibodies that target and destroy platelets
can happen spontaneously or be triggered by something such as a viral infection
how does ITP present?
usually in kids under 10
usually a history of recent viral illness
symptoms develop over 24-48 hrs
- bleeding (eg from gums, epistaxis or menorrhagia)
- bruising
- petechial/purpuric rash caused by bleeding under the skin
how is ITP confirmed?
FBC showing a low platelet count
exclude other causes of low platelets such as heparin induced thrombocytopaenia and leukaemia
how is ITP managed in most cases?
most cases resolve spontaneously within 3 months usually just need monitoring until platelet count returns to normal
when is treatment needed in ITP?
if patient is actively bleeding or severe thrombocytopaenia (below 10)
how is ITP managed if required?
prednisolone
IV immunoglobulins
blood transfusions (if needed)
platelet transfusions (only work temporarily)
why do platelet transfusions only work temporarily in ITP?
bc the antibodies against platelets are still there so will begin destroying the transfused platelets as soon as they are infused
what advise should be given in ITP?
avoid contact sports
avoid IM injections and procedures such as lumbar punctures
avoid NSAIDs, aspirin and other blood thinners
advice on managing nosebleeds
seek help after any injury which could cause internal bleeding
possible complications of ITP?
chronic ITP
anaemia
intracranial and subarachnoid haemorrhage
GI bleed
what is thalassaemia?
autosomal recessive genetic defect in protein chains that make up haemoglobin resulting in varying degrees of anaemia depending on type and mutation
types of thalassaemia?
alpha thalassaemia = defect in alpha globin chains
beta thalassaemia = defect in beta thalassaemia chains
what happens to RBCs in thalassaemia?
RBCs are more fragile and break down more easily
spleen acts as a sieve to filter the blood and remove older blood cells
in thalassaemia there is lots of old destroyed RBCs so the spleen has to filter far more and results in splenomegaly
what bony features can be seen in thalassaemia and why?
pronounced forehead and malar eminences (cheek bones)
due to fact that bone marrow expands to produce extra RBCs to compensate for the chronic anaemia
also causes susceptibility to fractures
potential signs and symptoms of thalassaemia?
microcytic anaemia (low MCV) fatigue pallor jaundice gallstones splenomegaly poor growth and development pronounced forehead and cheekbones more frequent fractures
how is thalassaemia diagnosed?
FBC - shows microcytic anaemia
haemoglobin electrophoresis - shows globin abnormalities
DNA testing - can show genetic abnormality
is thalassaemia screened for?
yes
all pregnant women are offered screening for thalassaemia at booking
how does iron overload occur in thalassaemia?
faulty creation of RBCs
recurrent transfusion and increased absorption of iron in the gut (as a response to anaemia)
how is iron overload monitored in thalassaemia?
patients have serum ferritin levels monitored to check for iron overload
how is iron overload managed in thalassaemia?
limiting number of transfusions
iron chelation
iron overload in thalassaemia causes similar effects to haemochromatosis, what are these?
fatigue liver cirrhosis infertility impotence heart failure arthritis diabetes osteoporosis and joint pain
what causes alpha thalassaemia?
defects in gene encoding for alpha globin chains
gene on chromosome 16
how is alpha thalassaemia managed?
monitor FBC monitor for complications blood transfusions splenectomy may be performed bone marrow transplant can be curative
what causes beta thalassaemia?
defect in gene encoding for beta globin chains
gene on chromosome 11
3 types of beta thalassaemia and how do they occur?
thalassaemia minor / intermedia / major
different types exist bc the gene defect can either consist of abnormal copies of the gene that retain some function of deletion of the gene where there is no function at all in the beta globin protein
what causes beta thalassaemia minor?
patients are carriers of abnormally functioning beta globin gene
one normal and one abnormal copy of the gene
effects of beta thalassaemia minor?
causes a microcytic anaemia
patients usually only need monitoring and no active treatment
what causes thalassaemia intermedia?
two abnormal copies of the beta globin gene
can either be 2 defective genes or one defective + one deletion gene
effects of beta thalassaemia intermedia?
causes a more significant microcytic anaemia
patients need monitoring and occasional blood transfusions and potentially some iron chelation when they need more transfusions
what causes thalassaemia major?
2 deletion genes
no functioning beta globin chains at all
(most severe type)
effects of beta thalassaemia major?
severe microcytic anaemia
splenomegaly
bone deformities
how is beta thalassaemia major managed?
regular transfusions
iron chelation
splenectomy
bone marrow transplant can potentially be curative
