Many of these patients currently take anticoagulant drugs such as Warfarin, which lower the risk of heart attacks or strokes by reducing the blood’s ability to clot.
Although these drugs reduce the risk of dangerous blood clot formation within blood vessels (thrombosis), they also affect normal wound healing, leaving patients at risk of lethal bleeding if they injure themselves in any way.
Now, a team of scientists from the UK, Sweden, Germany, Holland and the USA have discovered that the molecule polyphosphate can affect blood clot formation within veins and arteries without changing our ability to heal.
The findings, published this week in the journal Cell, are the first to show that polyphosphate activates a blood clotting agent called factor XII which is involved in the formation of harmful clots within blood vessels. But factor XII is not involved in surface wound healing and therefore reducing its levels in the body would not increase the risk of excessive bleeding.
The discovery opens up opportunities for drug development, according to Dr Nicola Mutch from the University of Leeds who carried out the UK branch of the research.
“The challenge in designing treatments to reduce thrombosis is getting the balance right. We need to find an appropriate drug level or target which causes enough anticoagulation to prevent risk of heart attack or stroke but with minimal bleeding side effects,” she explains.
“Our work suggests polyphosphate or factor XII could be potential new targets, as neither seems to affect our ability to heal naturally, so drugs based on these molecules could offer a major improvement on existing treatments.”
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Notes to editors
1. The paper – Muller et al., Platelet Polyphosphates Are Proinﬂammatory and Procoagulant Mediators In Vivo – will be published in Cell on December 11, 2009. A copy of the paper is available on request.
2. Dr Nicola Mutch is an Independent Research Fellow in Cardiovascular Medicine, in the Faculty of Biological Sciences, University of Leeds.
3. The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over 150 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty is ranked 4th in the UK (Nature Journal, 457 (2009) doi :10.1038/457013a) based on results of the 2008 Research Assessment Exercise (RAE). The RAE feedback noted that “virtually all outputs were assessed as being recognized internationally, with many (60%) being internationally excellent or world-leading” in quality. The Faculty’s research grant portfolio totals some £60M and funders include charities, research councils, the European Union and industry. www.fbs.leeds.ac.uk
4. The 2008 Research Assessment Exercise showed the University of Leeds to be the UK’s eighth biggest research powerhouse. The University is one of the largest higher education institutions in the UK and a member of the Russell Group of research-intensive universities. The University’s vision is to secure a place among the world’s top 50 by 2015. www.leeds.ac.uk