Heamaglobinopathy - sickling disorders

Question 1

pathophysiology of sickling disorders

Answer 1

point mutation in codon 6 of the beta globin gene that substitutes glutamine to valine producing beta s

this alters the structure of the resulting Hb->HbS

HbS polymerises if exposed to low oxygen levels for a prolonged period

this distorts the red cell damaging the RBC membrane

Question 2

what is there of the affected RBCs

Answer 2

characteristic appearance

Question 3

Sickle trait (HbAS) is what 
symptoms 
how many people 
when does it sickle
blood film 
types

Answer 3

one normal one abnormal beta gene
asymp carrier state
few clinical features as HbS levels too low to polymerise
may sickle in severe hypoxia such as high amplitude, under anaesthesia
blood film normal
mainly HbA, HbS <50%

Question 4

sickle cell anaemia HbSS
inheritance 
HbS, HbA
what is sickle crisis
symptoms

Answer 4

two abnormal beta genes
autosomal recessive

HbS>80% no HbA

episodes of tissue infarction due to vascular occlusion

symptoms depend on site and severity - digits, bone marrow, lung, spleen, CNS, pain can be extremely severe

Question 5

chronic haemolytic

Answer 5

shortened RBC lifespan

sequestration of sickled RBCs in liver and spleen

Question 6

hyposlenism

Answer 6

due to repeated splenic infarcts

Question 7

sickle vaso occlusion leads to what

Answer 7

tissue ischaemia and severe pain

Question 8

precipitants of sickle crisis

Answer 8

hypoxia
dehydration
infection
cold exposure
stress/fatigue

Question 9

treatment of painful crisis

Answer 9

opiate analgesia 
hydration 
rest 
oxygen 
antibiotics if infection 
red cell transfusion in severe crises e.g. chest crisis or neurological symptoms

Question 10

longterm effects

Answer 10

impaired growth
risk of sepsis
risk of organ damage - pulmonary htn, renal dx, avascular necrosis, leg ulcers, stroke

Question 11

long term treatment

Answer 11

hyposplenism - reduce risk of infection

• prophylactic penicillin
• vaccination: pneumococcus, meningococcus, haemophilia

folic acid supplementation (increased RBC turnover leads to an increased demand)

hydroxycarbamide can reduce severity of disease by inducing HbF production

Question 12

sickle cell disease

Answer 12

compound heterozygosity for HbS and another Beta chain mutation e.g.

• HbS/beta thalassaemia
• HbSC disease; milder but increased risk of thrombosis