Principal Investigator & Supervisor: Dr J Malcolm Walker
Research Fellow: Dr Emmanuel Ako
Post: September 2013 to September 2015
National Institute of Health Services Research / Biomedical Research Centre (BRC) Award :64224
Sickle cell disease (SCD) is a genetic disease affecting the production of haemoglobin. It has life-long consequences for the affected individuals with multiple organ involvement, including the heart and circulation and a reduced life expectancy.
Although all SCD patients share the same genetic haemoglobin defect, the clinical features vary enormously between individuals. This would suggest other factors, unrelated to the haemoglobin mutation, play an important role in how the disease manifests itself in an individual, particularly after the age of 40 years.
A large body of evidence supports the notion that complications can be separated into those that are due to blocking of blood vessels (vaso-occlusive) or due to destruction of haemoglobin containing red blood cells in the circulation (haemolysis). This explanation fits into the understanding of the haemoglobin mutation that characterises SCD.
The improved survival of SCD patients in developed countries is in large part due to improved management of infections and by reducing the number of circulating sickle red cells by undertaking exchange transfusions. Drugs such as hydroxyurea may also increase the proportion of normal red cells in the blood.
As SCD patients survive decades longer than they previously would have, there is an emerging range of cardiovascular complications which are associated with severe heart and circulatory problems as well as premature mortality (on average >20 years of life lost compared to non-SCD peer groups).
The manner in which the heart and circulation are affected is incompletely understood and is currently a subject of debate and the subject of this research effort. Novel methods of assessing heart function at rest and during exercise, using magnetic resonance scanning (MRI) methods are being developed with the specialist unit at Great Ormond Street Hospital (Dr Vivek Muthurungam).
Data analysed by Dr Ako, worryingly suggests that current therapies directed at correcting haemoglobin levels have so far not appeared to prevent heart and circulation complications. This data is in preparation for presentation at major international medical conferences:
- American College of Cardiology 64th Annual Scientific Session: San Diego USA; 14-16 March 2015
- Society of Cardiac Magnetic Resonance Annual Scientific Congress: Nice, France; 5-7 February 2015
- British Cardiovascular Society Annual Scientific Congress: Manchester; 8-10 June 2015