Hunting the genes that cause platelet bleeding disorders

Red blood cells

Press release issued: 5 January 2010

A £1.4 million grant awarded by the British Heart Foundation (BHF) to a collaborative group which includes researchers at Bristol, seeks to identify the faulty genes that underlie bleeding in families with abnormal blood platelet function.

Scientists know very little about what causes platelet bleeding disorders. A £1.4 million grant awarded by the British Heart Foundation (BHF) seeks to identify the faulty genes that underlie bleeding in families with abnormal blood platelet function.

The research is a five-year collaboration between University of Bristol researchers Dr Andrew Mumford in the Bristol Heart Institute and Dr Stuart Mundell, Department of Physiology and Pharmacology and Professor Steve Watson and Dr Paul Gissen, University of Birmingham and Dr Martina Daly, University of Sheffield.

Platelets are small cells in the bloodstream that become activated and clump together at areas of injury to prevent excessive bleeding. When this happens in diseased blood vessels, it can cause a heart attack or stroke, which together are the leading cause of death in the western world. Understanding the process of platelet activation better will help scientists to design new anti-platelet drugs that could prevent heart attacks and strokes.

One approach is to study people with rare disorders that stop their platelets from activating properly. These patients can experience dangerous excessive bleeding after injury or surgery, as well as day-to-day issues like easy bruising and severe nose bleeds.

Very little is known about what causes these platelet bleeding disorders. In a handful of patients, scientists have identified that the problem stems from mutations in genes involved in the platelet activation process. The researchers will study more than 400 patients with platelet bleeding disorders to look for more causative gene defects.

Dr Mumford, commenting on the grant award, said: "The results from detailed functional testing of platelets and from cell biology and molecular analyses will identify novel proteins and domains within known proteins that are critical for the function of platelets.

"Greater understanding of platelet biology will help in the development of new anti-thrombotic drugs for the treatment and prevention of disorders such as heart attacks and stroke."

Genes hold instructions for making proteins, which carry out the functions of a cell through series of interactions that scientists call "pathways". The collaborative team will first study each patient's platelets in detail to find out which pathways are defective, helping them to narrow down their search for the faulty genes. Each gene that they identify will increase their understanding of how the protein it encodes is involved in platelet function.

The team expects to find around 60 genes. This information will help identify patients with bleeding disorders, who might react badly to currently used blood-thinning medications.

Further information

The British Heart Foundation £1.4 million grant, awarded on 14 September 2009, is for a five-year research programme entitled Mapping and functional investigation of genetic mutations in patients with mild platelet bleeding disorders.

The research group include University of Bristol researchers Dr Andrew Mumford in the Bristol Heart Institute and Dr Stuart Mundell, Department of Physiology and Pharmacology and Professor Steve Watson and Dr Paul Gissen, University of Birmingham and Dr Martina Daly, University of Sheffield.

The Bristol Heart Institute is made up of over 200 researchers and clinicians, from eight different departments in the University of Bristol, spanning three faculties, and from associated Bristol NHS Trusts. Research income is generated from grants, with the British Heart Foundation being the Institute's main funder.

As well as improving collaboration between scientists and clinicians within the Institute, the aim is to communicate research findings to the public.

The British Heart Foundation (BHF) is the nation's heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease.

Please contact Joanne Fryer for further information.