Thrombus Stability
Research type
Research Study
Full title
“Role of fibrin biofilm and clot network architecture in thrombus stability”
IRAS ID
266449
Contact name
John P Greenwood
Contact email
Sponsor organisation
University of Leeds
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
Thrombosis is the final step of the atherosclerotic process, resulting in significant mortality and morbidity in patients with cardiovascular disease. Blood clots causing heart attacks and strokes are a leading cause of death worldwide. Added to this is the significant burden associated with venous thrombosis following surgery, hospitalisation, or as a result of cancer, pregnancy or immobilisation. It is estimated that in the UK alone, up to 200,000 deaths per year are caused by arterial thrombosis, and ~25,000 deaths by venous thrombosis and associated embolic complications. While arterial and venous thrombosis have different causes, both share the common end-point mechanism of the formation of a blood clot that occludes blood vessels, causing tissue ischaemia, organ malfunction and ultimately death. The main treatments for thrombosis are based on anticoagulation to inhibit thrombin generation or activity, and/or agents that reduce platelet aggregation. However, all antithrombotic treatments incur a significant risk of bleeding. Clot architecture has been implicated in both venous and arterial thrombosis, making it an attractive novel target.
Our working hypothesis is that fibrin, and in particular the architecture of the fibrin polymer, plays a fundamental role in thrombosis and thrombus stability. Our pilot data indicate that different fibrin structures drive distinct mechanisms involved in haemostasis and thrombosis. We wish to investigate these mechanisms in detail, and exploit them in order to develop new treatments for thrombotic disorders, while improving current treatments in terms of effectiveness and safety profile, particularly in relation to bleeding risk. We suggest that fibrin clot architecture can be exploited to reduce the significant burden of thrombosis in patients with cardiovascular disease.Summary of results
We recently discovered a new structure on blood clots, a protein film that provides a natural barrier for cells to move out of the clot, or for microbic organisms to move in. These findings were made on clots that help to stem, bleeding and seal skin wounds. However, there was also anecdotal evidence that similar film structures also occurred on occlusive thrombi from patients with acute heart attacks. We therefore aimed to study this systematically in thrombi obtained from 45 patients with acute heart attacks. We found that all thrombi were covered with fibrin film, with a range of 5-60% total surface coverage by fibrin film, average 15%. We also found that fibrin film coverage of the thrombi increased with the time elapsed between onset of the heart attack and thrombus retrieval (thrombectomy), or in other words age of the thrombus. These findings indicate that film coverage increases with time and may make clots less amenable to breakdown with clot-busting drugs.
REC name
East of Scotland Research Ethics Service REC 2
REC reference
19/ES/0106
Date of REC Opinion
10 Sep 2019
REC opinion
Favourable Opinion