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Structural And Functional Studies On The Interaction Between Alpha2-Antiplasmin And Plasmin
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Fibrinolysis is the process by which the body dissolves clots. In this proposal we aim to investigate how the fibrinolysis inhibitor alpha2-antiplasmin interacts with the clot dissolving protease enzyme plasmin. These data will be useful for developing new approaches to accelerate plasmin-mediated clot breakdown.
An International Randomised Trial Of Low-dose Aspirin To Prevent Recurrent Venous Thromboembolism (INSPIRE)
Funder
National Health and Medical Research Council
Funding Amount
$1,989,986.00
Summary
Patients who develop venous blood clots or pulmonary embolism, without an underyling cause, are at very high risk of recurrence once anticoagulant treatment (warfarin) is discontinued. The international INSPIRE trial is assessing whether low-dose aspirin treatment (a simple and cheap alternative to warfarin) is effective and safe in preventing further blood clots. If proven effective, aspirin could potentially prevent thousands of patients worldwide from experiencing such events.
Low-dose Aspirin To Prevent Recurrent Venous Thromboembolism (ASPIRE) Study: A Multicentre Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,108,600.00
Summary
In approximately one-third of patients who develop deep vein thrombosis or pulmonary embolism, this event is 'unprovoked' . These patients are at very high risk of recurrence once treatment with warfarin is discontinued. Warfarin treatment is very effective to prevent recurrence but is inconvenient because it has to be very closely monitored with blood tests and also causes serious bleeding complications in a significant number of patients. There are currently no other treatments available to pr ....In approximately one-third of patients who develop deep vein thrombosis or pulmonary embolism, this event is 'unprovoked' . These patients are at very high risk of recurrence once treatment with warfarin is discontinued. Warfarin treatment is very effective to prevent recurrence but is inconvenient because it has to be very closely monitored with blood tests and also causes serious bleeding complications in a significant number of patients. There are currently no other treatments available to prevent recurrent thrombosis. Low-dose aspirin treatment offers a simple, inexpensive, and widely practicable alternative to warfarin but has not yet been proven to be effective for preventing recurrent thrombosis. This study will investigate the effectiveness and safety of aspirin to prevent recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism who have completed standard anticoagulation with heparin and warfarin. If proven to be effective, aspirin could potentially prevent thousands of patients from experiencing recurrent venous thromboembolism or fatal pulmonary embolism worldwide and also save millions of dollars in health care costs each year.Read moreRead less
Susceptibility To Venous Leg Ulceration: Investigation Of The First Genetic Risk Factor
Funder
National Health and Medical Research Council
Funding Amount
$291,000.00
Summary
This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previ ....This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previous deep vein thrombosis. However, not all patients with a deep vein thrombosis or other forms of venous disease will go on to develop a venous ulcer. Our preliminary results show that patients with a venous ulcer have a greater frequency of this gene than healthy controls without venous ulcers, and suggest that patients with the candidate gene have a greater risk of developing venous ulceration. In this study we aim to determine whether the gene itself contributes to ulcer susceptibility or whether it is just a marker of that susceptibility. We can do this by assessing related genes and the levels of the protein produced by this gene. In this study we also aim to assess whether patients with a proven deep vein thrombosis are more likely to develop venous ulceration if they have the candidate gene. These studies have the potential to lead to the development of a diagnostic screening test for use in patients with venous disease, to assess the likelihood of developing leg ulceration. This will enable more active treatment to prevent leg ulceration. If this gene contributes to ulcer susceptibility new specific treatments may be developed for ulcer management and prevention.Read moreRead less
The Molecular Basis For The Increased Incidence Of Thrombosis Associated With The Prothrombin G20210A Gene Polymorphism
Funder
National Health and Medical Research Council
Funding Amount
$213,838.00
Summary
Prothrombin is an important enzyme involved in the formation of blood clots. Recently, a mutation was discovered in the prothrombin gene. This mutation occurs at a frequency of 2% in the normal population but occurs at an increased frequency (6%) in patients with thrombosis and is associated with an increase in the levels of prothombin in the blood. The position of this mutation in the prothrombin gene corresponds to the last residue of the prothrombin mRNA. We have preliminary data to suggest t ....Prothrombin is an important enzyme involved in the formation of blood clots. Recently, a mutation was discovered in the prothrombin gene. This mutation occurs at a frequency of 2% in the normal population but occurs at an increased frequency (6%) in patients with thrombosis and is associated with an increase in the levels of prothombin in the blood. The position of this mutation in the prothrombin gene corresponds to the last residue of the prothrombin mRNA. We have preliminary data to suggest that this mutation results in the prothrombin mRNA being more stable, which in turn allows for the production of more prothrombin protein, leading to an increased risk of developing a blood clot. The aim of this project is to explore the mechanisms leading to the elevated levels of prothrombin observed patients with this mutation.Read moreRead less
Improved Ways To Study The Effect Of Transient Exposures On The Risk Of An Illness, With Application To Flying And DVT
Funder
National Health and Medical Research Council
Funding Amount
$212,250.00
Summary
Improved methods of analysis will be developed to estimate the extent to which certain short-term activities trigger a particular illness and to determine who is most at risk. The new methods of analysis have many potential applications, including study of the effect of periods of intense exercise or intense alcohol consumption on the risk of a heart attack. Here we apply them to study the effect of air travel on illness due to blood clots in a vein (deep vein thrombosis, DVT), and the factors t ....Improved methods of analysis will be developed to estimate the extent to which certain short-term activities trigger a particular illness and to determine who is most at risk. The new methods of analysis have many potential applications, including study of the effect of periods of intense exercise or intense alcohol consumption on the risk of a heart attack. Here we apply them to study the effect of air travel on illness due to blood clots in a vein (deep vein thrombosis, DVT), and the factors that put individuals at greatest risk. The extra understanding that our improved analysis of the data provides will accelerate research into ways to minimise the risk of flight-induced DVT and implementation of preventative measures in the travel industry. This has the potential to prevent many cases, and deaths, because the number of flights taken, globally, by individuals in a year is now in the billions. Specifically, dependence of flight-induced DVT on age, sex, being pregnant, recent fractures and having certain cancers will identify individuals at greatest risk, while dependence on the duration of the flight will identify flights that present greater risk. The development of these new methods of analysis will make a lasting contribution to public health research, because they can be used to study many short-term-activity - illnesses combinations. The methods will see increasing applications because the type of data they rely on, namely the complete history of exposures over time periods, will increasingly become available as electronic recording of activities becomes more common place. For example, electronic records of flights are now almost universal and bookings at squash courts and other sporting venues are increasingly recorded electronically. The computer software to apply the new methods of analysis will be made available to other researchers, to promote studies of this type.Read moreRead less
Non-invasive Electrical Nerve Stimulation To Improve Healing Of Chronic Venous Leg Ulcers
Funder
National Health and Medical Research Council
Funding Amount
$206,210.00
Summary
Chronic venous leg ulcers are common in the elderly. They often last for many months or years, causing much suffering and expense (currently around $600,000,000 per year in Australia). As more and more Australians live into advanced age, more and more people will be troubled by leg ulcers, particularly as the likelihood of having a leg ulcer increases markedly in the very old. We have developed a painless, cheap treatment that improves wound healing. The treatment consists of electrical stimulat ....Chronic venous leg ulcers are common in the elderly. They often last for many months or years, causing much suffering and expense (currently around $600,000,000 per year in Australia). As more and more Australians live into advanced age, more and more people will be troubled by leg ulcers, particularly as the likelihood of having a leg ulcer increases markedly in the very old. We have developed a painless, cheap treatment that improves wound healing. The treatment consists of electrical stimulation of nerves that supply the wound. Low frequency current is passed through the skin from small battery powered stimulators. We have tested this technique in laboratory animals and in just a few older people with diabetes and have shown it is remarkably effective. We now plan to test this technique properly in a large study in older adults. If successful, the electrical stimulation could result in healing of wounds in relatively few weeks that otherwise would not heal for many months. Much suffering and expense would be avoided. As people age, nerve function deteriotes. Another part of the project will explore whether electrical nerve stimulation can improve damaged nerves themselves. This will provide interesting scientific insight about nerve repair and could lead to treatments for peripheral neuropathy that occurs in diabetes and other medical conditions. Australia needs to act on this now because the number of people aged over 65 will increase from around 2.3 million at present to over 6 million in the next half century. The increase in those over 85 will be even more marked with numbers increasing four fold to over one million people. Many of these people will experience severe impairment of their quality of life from leg ulcers that could be avoided, or at least minimized if a successful treatment is developed and made available to them. Similarly, much unnecessary expense could be avoided.Read moreRead less