Factor XII-dependent Thrombosis And Platelet Glycoprotein Ib
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
We will determine the value of targeting the interaction between a receptor unique to platelets, glycoprotein Ib, and two factors (XI and XII) in plasma involved in blood clotting, as a novel strategy to prevent clots that lead to heart attack-stroke. Our study is at the basic research-clinical interface and has the potential to improve our understanding of both bleeding in patients with Factor XI-XII defects and prevention of dangerous levels of clotting without affecting normal vessel repair.
Improving Warfarin Management- Identifying Risk Factors For Bleeding And Improving Monitoring Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$291,309.00
Summary
Warfarin is a drug commonly used in the elderly to prevent blood clots. While a very effective drug, it is also a dangerous drug and should be closely monitored. While we know many of the reasons why problems occur, we do not know whether organisation of care, mental health or social issues such as community support influence how well warfarin is managed. These are important questions to answer, so that we can make significant inroads into preventing death and disability from warfarin.
Regulation Of Inflammation And Thrombosis By Endothelial Protein C Receptor And Thrombomodulin In Xenograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$35,085.00
Summary
Pig-to-human organ transplantation may be the solution to the human organ shortage crisis. However, cross-species organ transplantation invariably results in graft destruction and rejection. Genetically modified mice expressing anti-rejection proteins will be tested to assess their effects and benefits on grafts. If such genes improve graft outcome, pigs with similar genetic modifications will be generated for the purposes of pig-to-primate organ transplantation studies.
Investigate Novel Functional Roles For PI 3-kinases In Platelets.
Funder
National Health and Medical Research Council
Funding Amount
$537,215.00
Summary
Platelets are small blood cells which have a well defined role in blood clotting. There is a growing body of evidence that platelets play an important role in a broad range of inflammatory diseases, and we have identified a key role for the platelet PI3K enzyme in controlling the pro-inflammatory function of platelets. This grant will examine the importance of PI3K in health and disease, and examine the potential therapeutic benefits of inhibiting platelet PI3K.
RCT Of Aspirin And Fish Oil For The Prevention Of Thrombosis In Arterio-venous Fistulae For Dialysis Access
Funder
National Health and Medical Research Council
Funding Amount
$1,869,190.00
Summary
This randomised, placebo-controlled clinical trial aims to determine whether the anti-platelet agents aspirin and fish oil, either alone or in combination, will effectively reduce the risk of early thrombosis (blood clots) in arterio-venous fistulae (AVF) that are used for accessing the circulatory system in dialysis. The trial is to be conducted by the Australasian Kidney Trials Network (AKTN). 1200 patients requiring haemodialysis who are scheduled to undergo creation of an AVF and are not cur ....This randomised, placebo-controlled clinical trial aims to determine whether the anti-platelet agents aspirin and fish oil, either alone or in combination, will effectively reduce the risk of early thrombosis (blood clots) in arterio-venous fistulae (AVF) that are used for accessing the circulatory system in dialysis. The trial is to be conducted by the Australasian Kidney Trials Network (AKTN). 1200 patients requiring haemodialysis who are scheduled to undergo creation of an AVF and are not currently taking anti-platelet agents will be recruited over 3 years. AVF is the accepted standard for haemodialysis patients because it utilises the patient's own artery and vein to allow repeated access to the vascular system with a minimal risk of complications. Failure of the AVF means the use of inferior permanent venous catheters or arterio-venous artificial grafts. These devices are more costly to insert, and have an increased risk of failure due to infection and thrombosis. Reducing this rate of failure by simple, cheap and readily available interventions has the potential to reduce these problems. Aspirin has been chosen because of its well-established anti-thrombosis effects. Fish oil has a number of biological effects which make it an attractive agent for the prevention of vascular access thrombosis. Study treatment will be aspirin 100 mg per day or matching placebo, and fish oil 4 gm daily or matching placebo, both commencing on the day prior to surgery and continued for 3 months. If the trial demonstrates a positive effect of either or both agents, this will lead to a reduction in thromboses, quicker time to working dialysis access, and less need for surgery.Read moreRead less
Development Of Recombinant RsolCD39-PSGL As A Novel Therapeutic With Anti-thrombotic And Anti-inflammatory Effects
Funder
National Health and Medical Research Council
Funding Amount
$186,367.00
Summary
Heart disease and stroke are due to a narrowing of arteries followed by occlusion, due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. The currently available drugs are often limited by the adverse reaction of bleeding. We will investigate the efficiency of a new drug to prevent clot formation and inflammation.
A Randomised, Controlled Trial Of 10% Dextran 40 In The Prevention Of Stroke Complicating Carotid Endarterectomy
Funder
National Health and Medical Research Council
Funding Amount
$200,667.00
Summary
The operation to remove blockages in the carotid arteries (carotid endarterectomy) is of proven benefit in the prevention of stroke. The procedure itself, however, unfortunately carries approximately a 1 in 20 risk of immediate and early postoperative stroke. Most strokes are caused by blood clots forming at the operation site, breaking off and travelling to the brain (embolism). The up front operative risk is usually accepted by most patients in order to achieve the significantly greater long t ....The operation to remove blockages in the carotid arteries (carotid endarterectomy) is of proven benefit in the prevention of stroke. The procedure itself, however, unfortunately carries approximately a 1 in 20 risk of immediate and early postoperative stroke. Most strokes are caused by blood clots forming at the operation site, breaking off and travelling to the brain (embolism). The up front operative risk is usually accepted by most patients in order to achieve the significantly greater long term benefits of future stroke risk reduction. This study is designed to test a medication (dextran) thought to possibly prevent stroke associated with the operation. Dextran acts in part, by preventing blood clots forming at the operation site . In a pilot study undertaken by the researchers, dextran significantly reduced the downstream shedding of small blood clots (microemboli) detected by monitoring brain arteries using specialised ultrasound techniques. It remains to be proven, however, whether this effect on microemboli actually translates into the prevention of stroke complicating surgery. The DICE (Dextran In Carotid Endarterectomy) Trial aims to assess whether dextran can reduce the risk of stroke associated with carotid surgery by 50% or more. It has important implications for the increasing numbers of Australians being offered this operation (5,000-6,000 each year). If the therapy is proven effective there will be the potential to prevent 350-450 strokes and stroke related deaths each year.Read moreRead less
The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment o ....The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment of heart attack and stroke. The currently available drugs are not universally effective and their use is often limited by adverse reactions. In this submission, we propose to investigate the efficiency of a new drug that will prevent clot formation and will also tackle inflammation. This drug is a derivative of an enzyme that is already present on platelets and cells that line blood vessels. We have modified this enzyme in a manner that will increase the enzyme activity on the surface of platelets and on the cells that line the blood vessel wall. We will thoroughly study this new drug by performing experiments in the laboratory as well as by studying its effect in mice.Read moreRead less
A Case Control Study Investigating Factors Contributing To The Risk Of Bleeding In Patients Receiving Warfarin Therapy
Funder
National Health and Medical Research Council
Funding Amount
$572,242.00
Summary
Warfarin is a drug commonly used in the elderly to prevent blood clots. Blood clots can lead to stroke. While a very effective drug, it is also a dangerous drug because it can lead to thin blood which makes it more likely that they will bleed. For this reason, the drug should be closely monitored. We know that many people do suffer catastrophic bleeds because the blood is too thin directly as a result of taking warfarin. Some of the reasons for these bleeds are well known; they may be taking dru ....Warfarin is a drug commonly used in the elderly to prevent blood clots. Blood clots can lead to stroke. While a very effective drug, it is also a dangerous drug because it can lead to thin blood which makes it more likely that they will bleed. For this reason, the drug should be closely monitored. We know that many people do suffer catastrophic bleeds because the blood is too thin directly as a result of taking warfarin. Some of the reasons for these bleeds are well known; they may be taking drugs that interact with warfarin, they may have problems with their liver or kidney which affects the body's ability to get rid of it, they may have suffered a fall, to name a few. Studies done overseas have suggested that people are more likely to have a bleed if they do not know how to properly manage their tablets, if they are depressed, if they have no helpers to support them or if their care is not well organised. In Australia, we do not know what impact the organisation of care has on whether a person's warfarin is well managed. We do not know the impact that depression has on their care, or whether people are more likely to have pooorly controlled warfarin if they have few community ties. These are importnat questions to answer, so that we can make significant inroads into preventing death and disability from warfarin.Read moreRead less