Sickle Cell disease

Question 1

What is the epidemiology of sickle cell disease?

Answer 1

More than 1 in 2000 live births
More common in black Africans - 8% carry the gene -sickle cell trait offers a protective effect against malaria in endemic regions and this has led to positive selection for the gene mutation; sickle cell disease however does NOT confer the protection of the trait and infection with malaria is likely to be more severe due to splenic hypo-functioning

Usually diagnosed on newborn blood spot or before; strong Hx indicators

Question 2

What is the aetiology and pathophysiology of sickle cell disease?

Answer 2

Autosomal recessive - HbSS = sickle cell disease; HbSA = carrier - chromosome 11

RBCs become sickle shaped in low O2 - due to Hb chains polymerising with others - bends gross form of RBC - dont pass though vessels as easily, may become sequestered/clog microvasculature - ‘crises’

Question 3

What are some problems associated with sickle cell disease?

Answer 3

Anaemia:
Cardiomegaly
Low sats
High WCC

Infarction:
Pain crises
Strokes

Infection/sepsis:
Asplenia from filtering abnormal RBCs
Any fever is a serious sign -seek help

Splenic sequestration

Acute Chest

Dactylitis - often first sign presenting in babies

Iron overload

Question 4

What is an aplastic crisis?

Answer 4

A decrease in Hb ≥3g/dl with reticulocytopenia without evidence of hemolysis, usually from parvovirus B19

Can also be post op - need to maintain good hydration

Question 5

What is functional asplenia?

Answer 5

Functional asplenia:
Poor functioning of spleen due to overwork processing RBCs; leads to increased
infections with encapsulated bacteria e.g. H.influenzae, Strep. pneumoniae and N.meningitidis - as they lack IgM memory B cells necessary to defend against these bugs

Question 6

What is splenic sequestration?

Answer 6

Splenic sequestration:

Blood pools in spleen - hypovolaemia; treat with fluids and transfusion

Question 7

What is an acute chest?

Answer 7

Could be due to infection or infarction

25% occur after surgery

Presentation: pain, hypoxia, fever, neurological manifestations

Management:
Admission, 2-3 days in ICU, 10 days in hospital; transfusion, IV fluids, O2, Abx etc

25% of premature deaths in SCD

Question 8

What are the blood results for sickle cell disease?

Answer 8

Hb - low
Reticulocytes - raised
WCC - raised even w/o infection
Ferritin - raised

Question 9

How do you manage sickle cell disease?

Answer 9

Hydroxycarbamide/hydroxyurea:
Increases levels of HbF - carries O2 at a lower tension so able to release and absorb more readily; teratogenic in pregnancy

Antibiotics: penicillin
Children - from 2 months old until they’re at least 5 years old
Adults - if ever had pneumonia or a splenectomy

Transfusions:
To prevent stroke in those at high risk

Stem cell transplant:
Curative if good donor found; reserved for serious cases e.g. where multiple strokes have occurred/frequent crises/long term transfusions required

Question 10

What is iron overload and how is it managed?

Answer 10

Consequence of long-term hemolysis and/or transfusions (as breakdown releases Fe into circulation)

Affects all organs: 
Chronic liver disease/cirrhosis 
DM - 'bronze' diabetes (browning of skin)
Heart failure, arrhythmia 
Hypogonadism 

Monitoring:
Ferritin - raised
Imaging - e.g. bone infarcts, strokes, chest crises

Management: Chelation when necessary - desferrioxamine

Question 11

How do you manage pain in sickle cell disease?

Answer 11

Frequent - if mild treat with paracetamol, NSAIDS

If severe, give morphine

Oxygen and fluids as required

Question 12

What is important in the management of infections in sickle cell disease?

Answer 12

Need to ensure vaccinated - pneumonoccal, influenza, meningococcal - as are at a higher risk for sepsis

Need prophylactic penicillin - again to reduce mortality rate from sepsis - adherence might not be great due to infection with C.diff secondary to Abx use