Researchers in the UK and US report in the New England Journal of Medicine this week (9 August) the results of a study in children which may explain why patients with meningococcal septicaemia develop widespread clotting within blood vessels leading to death or loss of limb and digits.
The team from Imperial College and St Mary’s Hospital, London, in collaboration with research groups at the University of Bristol, UK, and Oklahoma, USA, say that their work offers new directions for treatment of the blood poisoning form of meningitis.
In healthy individuals, a number of proteins are present in the blood which act to prevent clots forming in veins and arteries. One of these is a recently identified protein called Protein C, which when activated is a powerful inhibitor of clot formation.
The NEJM study of 21 children establishes for the first time that patients suffering from meningococcal septicaemia have lost two key proteins (thrombomodulin and endothelial Protein C receptor) required to activate Protein C on the lining of blood vessels.
This serious defect leads to an inability to control clotting within arteries and veins and opens the way to widespread clot formation, a hallmark of meningococcal septicaemia, often visible as rashes on the skin.
To date the development of effective treatments to prevent or reverse this clot formation has been hampered by a lack of understanding of the mechanisms involved.
Leader of the study Professor Michael Levin of Imperial College said:
“Our study has identified a key mechanism involved in the devastating complications of meningococcal disease, and offers new insights into how the disease might best be treated.
“A defect in the activation of Protein C could, theoretically, be treated by administration of Protein C in its active form, thus by-passing the requirements for activation on the surfaces of blood vessels.”
Clinical trials are currently underway to assess the safety and feasibility of this treatment.
Denise Vaughan, Chief Executive of funders Meningitis Research Foundation said:
“We are delighted with the outcome of this research which has the potential to prevent death and disability from meningitis and septicaemia.”
The authors of the paper are Dr Saul Faust, Professor Michael Levin, Odile Harrison, Dr Robert Goldin and Dr Sheila Kondaveeti (Imperial College and St Mary’s Hospital, UK); Dr Charles Esmon and Marion Lockhart (Oklahoma Medical Research Foundation, USA); Dr Zoltan Lasik (University of Oklahoma Health Sciences Center, USA); and Dr Robert Heyderman (University of Bristol, UK).
The programme of research has been supported by a grant from the Meningitis Research Foundation grant in excess of UKP700,000, with additional support via a training fellowship from the Medical Research Council.
Materials provided by Imperial College Of Science, Technology And Medicine. Note: Content may be edited for style and length.
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