Paeds - Haematology

Question 1

what makes up adult haemoglobin?

Answer 1

4 protein sub-units made of two pairs of sub-units

2 alpha and 2 beta sub-units

Question 2

what makes up foetal haemoglobin?

Answer 2

4 protein sub-units made up of 2 alpha and 2 gamma sub-units

Question 3

why does foetal Hb need to be different?

Answer 3

adult Hb picks up O2 in the lungs

foetal Hb picks up O2 in the placenta and has to steal it from mothers Hb

Question 4

which has a greater affinity for O2, adult or foetal Hb?

Answer 4

foetal (o2 binds easier and is more reluctant to let go basically)

Question 5

adult vs foetal Hb on oxygen dissociation curve?

Answer 5

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)

Question 6

how does Hb change during development?

Answer 6

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

Question 7

how does Hb change after birth?

Answer 7

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

Question 8

how is foetal HB affected in sickle cell disease?

Answer 8

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)

Question 9

what can be used to increase production of HbF in patients with sickle cell anaemia?

Answer 9

hydroxycarbamide

has protective effect against sickle cell crises and acute chest syndrome

Question 10

what is sickle cell anaemia?

Answer 10

genetic condition causing sickle (crescent) shaped RBCs which makes them more fragile and easily destroyed leading to a haemolytic anaemia

Question 11

what causes sickle cell anaemia?

Answer 11

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

Question 12

sickle cell trait vs disease?

Answer 12

one cope of abnormal gene for beta globin = sickle cell trait (usually asymptomatic)
two copies = sickle cell disease (symptomatic)

Question 13

how is sickle cell disease related to malaria?

Answer 13

more common in patients from areas traditionally affected by malaria
having one cope of the gene (sickle cell trait) reduces severity of malaria

Question 14

how is sickle cell diagnosed?

Answer 14

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

Question 15

possible complications of sickle cell disease?

Answer 15

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

Question 16

general management of sickle cell disease?

Answer 16

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

Question 17

what is a sickle cell crisis?

Answer 17

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

Question 18

what can trigger sickle cell crisis?

Answer 18

infection
dehydration
cold
significant life events

Question 19

how is sickle cell crisis managed?

Answer 19

supportively

• treat any infection
• keep warm
• keep hydrated (may need IV fluids)
• simple analgesia
• treat priapism with penile aspiration

Question 20

4 types of sickle cell crisis?

Answer 20

vaso-occlusive crisis (AKA painful crisis)
splenic sequestration crisis
aplastic crisis
acute chest syndrome

Question 21

what is a painful crisis?

Answer 21

causes by sickle shaped RBCs clogging capillaries and causing distal ischaemia

Question 22

symptoms of painful crisis?

Answer 22

pain
fever
symptoms of triggering infection (if present)
can cause priapism in men by trapping blood in penis

Question 23

what can cause painful crisis?

Answer 23

dehydration
infection
high haematocrit

Question 24

what is splenic sequestration crisis?

Answer 24

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

Question 25

how is splenic sequestration crisis managed?

Answer 25

emergency supportive management blood transfusions and fluid resuscitations used to treat anaemia and shock splenectomy used as preventative measure in cases of recurrent crisis

Question 26

what is an aplastic crisis?

Answer 26

where there is temporary loss of the creation of new blood cells leads to significant anaemia

Question 27

what usually triggers aplastic crisis?

Answer 27

parovirus B19

Question 28

how is aplastic crisis managed?

Answer 28

supportive blood transfusions if needed resolves spontaneously within a week

Question 29

how is acute chest syndrome diagnosed?

Answer 29

diagnosis requires presence of fever or resp symptoms + new infiltrates seen on CXR

Question 30

what can cause acute chest syndrome?

Answer 30

infection (eg pneumonia or bronchiolitis) | non-infective causes (eg pulmonary vaso-occlusion or fat embolism)

Question 31

how is acute chest syndrome managed?

Answer 31

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

Question 32

what is ITP?

Answer 32

condition where there is idiopathic (spontaneous) thrombocytopaenia causing a non-blanching purpuric rash

Question 33

what causes ITP?

Answer 33

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

Question 34

how does ITP present?

Answer 34

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

Question 35

how is ITP confirmed?

Answer 35

FBC showing a low platelet count | exclude other causes of low platelets such as heparin induced thrombocytopaenia and leukaemia

Question 36

how is ITP managed in most cases?

Answer 36

most cases resolve spontaneously within 3 months usually just need monitoring until platelet count returns to normal

Question 37

when is treatment needed in ITP?

Answer 37

if patient is actively bleeding or severe thrombocytopaenia (below 10)

Question 38

how is ITP managed if required?

Answer 38

prednisolone IV immunoglobulins blood transfusions (if needed) platelet transfusions (only work temporarily)

Question 39

why do platelet transfusions only work temporarily in ITP?

Answer 39

bc the antibodies against platelets are still there so will begin destroying the transfused platelets as soon as they are infused

Question 40

what advise should be given in ITP?

Answer 40

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

Question 41

possible complications of ITP?

Answer 41

chronic ITP anaemia intracranial and subarachnoid haemorrhage GI bleed

Question 42

what is thalassaemia?

Answer 42

autosomal recessive genetic defect in protein chains that make up haemoglobin resulting in varying degrees of anaemia depending on type and mutation

Question 43

types of thalassaemia?

Answer 43

alpha thalassaemia = defect in alpha globin chains | beta thalassaemia = defect in beta thalassaemia chains

Question 44

what happens to RBCs in thalassaemia?

Answer 44

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

Question 45

what bony features can be seen in thalassaemia and why?

Answer 45

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

Question 46

potential signs and symptoms of thalassaemia?

Answer 46

``` microcytic anaemia (low MCV) fatigue pallor jaundice gallstones splenomegaly poor growth and development pronounced forehead and cheekbones more frequent fractures ```

Question 47

how is thalassaemia diagnosed?

Answer 47

FBC - shows microcytic anaemia haemoglobin electrophoresis - shows globin abnormalities DNA testing - can show genetic abnormality

Question 48

is thalassaemia screened for?

Answer 48

yes | all pregnant women are offered screening for thalassaemia at booking

Question 49

how does iron overload occur in thalassaemia?

Answer 49

faulty creation of RBCs | recurrent transfusion and increased absorption of iron in the gut (as a response to anaemia)

Question 50

how is iron overload monitored in thalassaemia?

Answer 50

patients have serum ferritin levels monitored to check for iron overload

Question 51

how is iron overload managed in thalassaemia?

Answer 51

limiting number of transfusions | iron chelation

Question 52

iron overload in thalassaemia causes similar effects to haemochromatosis, what are these?

Answer 52

``` fatigue liver cirrhosis infertility impotence heart failure arthritis diabetes osteoporosis and joint pain ```

Question 53

what causes alpha thalassaemia?

Answer 53

defects in gene encoding for alpha globin chains | gene on chromosome 16

Question 54

how is alpha thalassaemia managed?

Answer 54

``` monitor FBC monitor for complications blood transfusions splenectomy may be performed bone marrow transplant can be curative ```

Question 55

what causes beta thalassaemia?

Answer 55

defect in gene encoding for beta globin chains | gene on chromosome 11

Question 56

3 types of beta thalassaemia and how do they occur?

Answer 56

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

Question 57

what causes beta thalassaemia minor?

Answer 57

patients are carriers of abnormally functioning beta globin gene one normal and one abnormal copy of the gene

Question 58

effects of beta thalassaemia minor?

Answer 58

causes a microcytic anaemia | patients usually only need monitoring and no active treatment

Question 59

what causes thalassaemia intermedia?

Answer 59

two abnormal copies of the beta globin gene | can either be 2 defective genes or one defective + one deletion gene

Question 60

effects of beta thalassaemia intermedia?

Answer 60

causes a more significant microcytic anaemia patients need monitoring and occasional blood transfusions and potentially some iron chelation when they need more transfusions

Question 61

what causes thalassaemia major?

Answer 61

2 deletion genes no functioning beta globin chains at all (most severe type)

Question 62

effects of beta thalassaemia major?

Answer 62

severe microcytic anaemia splenomegaly bone deformities

Question 63

how is beta thalassaemia major managed?

Answer 63

regular transfusions iron chelation splenectomy bone marrow transplant can potentially be curative