sickling disorders + blood films

Question 1

pathophysio of sickle cell anaemia

Answer 1

point mutation in codon 6 of the B globin gene that substitutes glutamine to valine producing Bs
- this alters the structure of the resulting Hb -> HbS (a2B2)

HbS polymerises if exposed to low oxygen levels for prolonged period -> this distorts red cell, damaging the RBC membrane

Question 2

sickle cell trait

Answer 2

one normal, one abnormal B gene (B/Bs)
<50%HbS
asymptomatic carrier state
- few clinical fx as HbS level too low to polymerise

may sickle in severe hypoxia - high altitude under anaesthesia
blood film normal

Question 3

sickle cell anaemia

Answer 3

autosomal recessive -
abnormal gene for beta globin on chromosome 11
- synthesis of abnormal haemoglobin chain -> HbS

crescent shapes red blood cells - makes RBCs fragile + more easily destroyed leading to haemolytic anaemia -> prone to sickle cell crises

Question 4

sickle cell trait vs sickle cell disease

Answer 4

trait = 1 copy of gene - asymptomatic <50% HbS, mainly HbA

disease = 2 abnormal copies, >80%Hbs, no HbA

Question 5

signs of sickle cell anaemia

Answer 5

chronic haemolysis - shortened RBC lifespan, block blood vessels causing infarction

sequestriation of sickled RBCs in liver + spleen
HYPOsplenism due to repeated splenic infarcts

**symptoms dont tend to develop until 4-6 months when abnormal HbS takes over from HbF

Question 6

definitive diagnosis of sickle cell anaemia

Answer 6

haemoglobin electrophoresis/HPLC

at risk pregnant women screen at pregnancy
new born screening heel prick test at 5 days of age

Question 7

complications of sickle cell anemia

Answer 7

anaemia, increased risk of infection
AVN - large joints like hip
priapism - painful long erections

sickle cell crisis
acute chest syndrome

Question 8

general management of sickle cell anaemia

Answer 8

avoid dehydration + triggers of crises

(hyposplenism) antibiotic prophylaxis = penicillin V (penoxymethypenicillin)
folic acid supplementation - increase RBC turnover so increase demand
hydroxycarbamide - used to stimulate production of HbF
- HbF doesnt lead to sickling of red blood cells -> protective against sickle cell crises + acute chest syndrome

blood transfusion for severe anaemia
bone marrow transplant can be curative

Question 9

sickle cell crisises

Answer 9

sickle cell anaemia is characterised by period of good health with itervening crises
umbrella term, mild to life-threatening
- can occur spontaneously or be triggered

thrombotic - vasoocclusive, painful
acute cchest syndrome
anaemia - aplastic, sequestrian
infection

Question 10

thrombotic crises (vaso-occlusive/painful)

Answer 10

caused by sickle shaped blood cells clogging capillaries causing distal ischaemia
- assoc with dehydration + raised haemocrit

diagnosed clinically

symptoms
- pain/fever
- infection signs (trigger)
- priapism - emergency, aspirate blood

Question 11

triggers/precipitants for sickle cell crisises

Answer 11

hypoxia - altitude
dehydration
cold
stress/fatigue/significant life events
infection

Question 12

acute chest syndrome

Answer 12

sickle crisis

diagnosis requires = fever or respiratory

Question 13

howell-jolly bodies

Answer 13

hyposplenism

Question 14

heinz bodies

Answer 14

G6PD deficiency

alpha thalassaemia

Question 15

schistocytes (“helmet cells”)

Answer 15

intravascular haemolysis
mechanical heart vvalve
disseminated intravascular coagulation

Question 16

pencil poikilocytes

Answer 16

iron deficiency anaemia

Question 17

spherocytes

Answer 17

hereditary spherocytosis
autoimmune haemolytic anaemia

Question 18

basophilic stippling causes

Answer 18

(more basophils in blood)

lead poisoning
thalassaemia
sideroblastic anaemia
myelodysplasia