TRI celebrates the 30th anniversary since its founding on October 4th, 2020.
Here we reflect on TRI’s past, present and future; beginning with the research programme started at King’s Hospital in 1965, through the establishment of an independent Institute in 1990, and how we will continue to build on our progress into the future.
Our guiding principle has remained a constant through the years: TRI serves to conduct multidisciplinary, global research of the highest quality in pursuit of the prevention and treatment of thrombosis.
Origins: The Thrombosis Research Unit (1965-89)
Professor Vijay Kakkar first took an interest in venous thromboembolism in the mid-60s upon discovering it was frequently responsible for the death of postoperative patients at Kings Hospital, London.
Professor Vijay Kakkar
With assistance from the radiology department at King’s he developed a diagnostic test (the FUT test). The information generated by the FUT (the natural history of postoperative DVT, and the definition of a ‘high risk’ patient group) laid the foundation for developing an effective method for prevention.
Studies at the time had shown that oral anticoagulant therapy was the most effective and proven method of preventing major venous thromboembolism. However, a major drawback of this form of therapy was the risk of serious bleeding both during and after surgery.
There was therefore an urgent clinical need for a drug that would be effective with a lower risk of bleeding. One promising approach was the use of low-dose heparin (a blood thinner).
In 1969, Professor Kakkar enlisted the support of a pharmaceutical company who agreed to provide supplies of heparin in support of the research. CHOAY Pharmaceuticals joined Kings Hospital Research Trust in providing support, initially for small-scale trials, and then for a pioneering International Multicenter Trial to provide unequivocal evidence that fixed low-dose heparin treatment prevented postoperative deaths and was free of bleeding complications.
Thrombosis Research Unit staff, 1974
These results indicated for the first time in a randomized clinical trial that anticoagulant therapy could prevent death and that this form of prophylaxis could now be recommended for use on a large scale to protect ‘high risk’ patients undergoing major elective surgery.
The critical findings of this landmark study were presented to the wider medical and scientific community at an International Heparin Symposium held at King’s College Hospital Medical School, 18–19 July 1975. The treatment was later refined to low molecular weight heparin – now thought to save the lives of at least 250 000 postoperative patients each year and dramatically reduce healthcare costs.
Additionally, the Medical Research Council awarded their first ever Programme Grant, enabling Professor Kakkar to establish a multidisciplinary team of researchers to expand the research (renewed in 1979 and 1984). During this 15-year period, the Thrombosis Research Unit increased their staff from 15 to 40 researchers.
30 Years: The Thrombosis Research Institute (1989 – present)
From 1989, the Thrombosis Research Unit became its own independent entity, the Thrombosis Research Institute. Professor Kakkar fought hard for seven years to secure funding and acquire a home for the TRI, on the King’s Road in Chelsea. PM Margaret Thatcher formally opened the building on October 4th, 1990.
The Emmanuel Kaye Building in 1990 and 2020
Professor Kakkar with PM Thatcher on opening day
1990s: range of lab work
When the Institute first opened in Manresa Road, Professor Kakkar established a number of laboratories drawn from different scientific disciplines in accordance with the remit of the Institute to carry out research in the area of the diagnosis, mechanism and treatment of thrombotic disease.
Such was the range of research activity over the course of those early years that at its peak there were 60 scientific staff. To give a sense of the range of research during that period, the labs included:
- A Molecular Genetics laboratory headed by Dr David Cooper. At that time, the use of molecular genetics was a burgeoning approach to the understanding of disease by identifying mutations in key proteins, which led to their dysfunction. The work in this laboratory also included computerized molecular modelling to show how particular mutations changed protein structures
- A large Cell Biology laboratory and Tissue Culture section headed by Dr Catherine Demoliou Mason investigated the properties of vascular cells in relation to thrombotic disease, with a spin off into an early investigation of the possibilities of Gene Therapy
- A Platelet Biochemistry laboratory was established alongside a Protein Structure laboratory investigating the properties of a snake venom blocker of platelet aggregation, dendroaspin (which was ultimately used by Dr Xinjie Lu in the development of a vaccine against atherosclerosis)
- A Clinical Coagulation and Fibrinolysis laboratory (headed by Dr Effie Melissari ) assessed the prothrombotic potential of individual patients. It was a fully automated and used in assessing patients during a number of large-scale clinical trials
- A Coagulation and Fibrinolysis laboratory (headed by Dr Mike Scully) undertook research into the basic mechanism of blood clotting and anticoagulants – particularly heparin. These biochemists worked closely with a Peptide Chemistry laboratory (overseen by Dr Goran Claeson and Dr John Deadman) in a search for new oral anticoagulants (ultimately a lead anticoagulant was identified, and this progressed further with the setting up of a new biotech company called Trigen)
Mike Scully showcases TRI work for Prince Philp
Modern era: Real World Evidence
In recent years, TRI has expanded to establish itself as a world leader in cardiovascular outcomes research and real-world evidence, as well as continue our lab research. We believe that the proven capacity of our research infrastructure to generate large volumes of high-quality data represents a substantial opportunity to make a substantial contribution to patients’ wellbeing.
Professor Kakkar stood down as institute director in 2010, succeeded by his son Professor Lord Ajay Kakkar. The persistence, collaboration and humility that characterised Professor Kakkar’s remarkable life’s work continue to guide TRI in how we conduct our research today.
TRI director Ajay K Kakkar
Our success in developing global research programmes such as GARFIELD-AF and GARFIELD-VTE (2009-19) has come through collaboration, with an active research network of more than 2,500 sites in 40 countries. Our research programmes have recruited over 78,000 patients and already captured over 130,000 years of outcomes data, while setting a high standard for data quality in large-scale prospective research (the TRI audit process was published in 2017).
GARFIELD involved 40 countries
Working in partnership with colleagues throughout the world as innovators in thrombosis, our work advances patient care and improves outcomes, thereby reducing healthcare costs and saving lives.
To separate our research operations from the work of the TRI charity, we have established a subsidiary, Cyte, to maintain and manage the TRI research network and provide the full range of clinical trial services to our research partners.
The future: where TRI can play leading role
At present TRI is engaged in three research projects related to COVID-19 (thrombosis is a damaging clinical manifestation of the disease). This includes an international multicenter trial in 10 countries called ETHIC, which will run for the next year.
The ETHIC will run in 10 countries
In London TRI’s laboratory research continues, focusing on fundamental mechanisms involved in blood coagulation, inflammation, and atherogenesis. TRI is also working on understanding the pathology that links cancer with VTE and developing treatment strategies, including ‘vaccines’ with the potential to prevent atherosclerosis, the main underlying cause of arterial thromboembolism. In the future, it may be possible to save countless lives by eliminating the development of one of the world’s biggest killer diseases with a simple inoculation.
We are also currently investigating emerging health technologies, including AI and machine learning. TRI envisions a future using intelligent modelling and innovative sources of data to develop cutting-edge models for optimal care.
What has not changed is our core research focus, our independence as an institute, our belief in global collaboration in executing research programmes and forging new solutions for the benefit of patients.