Heparin Induced Thrombocytopenia (HIT): Further Characterization Of Disease Mechanism Will Improve Patient Treatment
Funder
National Health and Medical Research Council
Funding Amount
$456,484.00
Summary
Thrombus formation occurs as a side effect of heparin treatment in many patients. This condition is called Heparin Induced Thrombocytopenia (HIT). The clots may be stabilised by secretions from cells called neutrophils. In this project we will study this possibility using a mouse model of HIT and will explore therapeutic approaches to inhibit clot stabilisation.
Platelet Receptor Regulation In Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$507,536.00
Summary
In response to bleeding, blood platelets use receptors to form a thrombus (blood clot) and block further loss of blood and aid tissue repair. People treated with heparin prior to surgery, can form autoantibodies that attack platelets, leading to thombus and thrombocytopenia (dangerous loss of circulating platelets). This is a significant clinical problem that is difficult to diagnose. We will determine how platelet receptor shedding can aid the diagnosis of heparin-induced thrombocytopenia.
A Study To Determine The Effects Of Heparin/ Low Molecular Weight Heparin In Neonates And Children.
Funder
National Health and Medical Research Council
Funding Amount
$193,000.00
Summary
Blood clots in newborns and children are becoming a more common problem. This is because many children with major illnesses are now surviving due to the remarkable advances in medical and surgical care. Blood clots in children can have devastating long term effects. Little is known about the best way to treat blood clots in children and most treatments are just extrapolated from adult treatment guidelines. This is unlikely to be the best treatment as the type and place of blood clots in children ....Blood clots in newborns and children are becoming a more common problem. This is because many children with major illnesses are now surviving due to the remarkable advances in medical and surgical care. Blood clots in children can have devastating long term effects. Little is known about the best way to treat blood clots in children and most treatments are just extrapolated from adult treatment guidelines. This is unlikely to be the best treatment as the type and place of blood clots in children are very different to adults. In addition, the blood clotting system in children is very different to that in adults. This is especially true for newborns. Over the last four years we have established the largest clinical treatment program for children with blood clots in Australia, and have completed the preliminary work that will enable us to now study a number of aspects of the treatment for blood clots in children. This project will specifically examine heparin and low molecular weight heparin which are the most commonly used antithrombotic (anti blood clot) drugs in children. We will determine the effect of age on the mechanism of action, the optimal drug level for treatment, the frequency of the most common side effect of heparin and do some preliminary work to determine alternative treatment options. Our study will provide the basis for more appropriate use of these drugs in children, which will improve the success of therapy and reduce the risk of complications, ultimately improving the survival and quality of life for sick children affected by blood clots.Read moreRead less
Use Of Snake Venom Prothrombin Activators In Blood Collection Tubes To Produce High Quality Serum To Improve Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$284,706.00
Summary
The timely availability of high quality serum and plasma samples are of the utmost importance for accurate biochemical analysis in a clinical setting. This requirement is particularly true for patients on anti-clotting therapeutic agents such as warfarin and heparin. In this study we will employ potent prothrombin activators purified from snake venom to enhance the clotting efficiency of blood for serum preparation for biochemical analysis.
Molecular Investigations Of Antithrombin Instability And Heparin Binding Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Thrombosis is a significant disease affecting a large number of people. The primary treatment for episodes of acute thrombosis is administration of the anticoagulant, heparin. The effector molecule through which heparin carries out its action is the serine proteinase inhibitor, antithrombin. This molecule regulates blood clotting by inhibiting the proteinases which carry out this process. Antithrombin is converted from a poor inhibitor of coagulation proteases to a very good inhibitor on binding ....Thrombosis is a significant disease affecting a large number of people. The primary treatment for episodes of acute thrombosis is administration of the anticoagulant, heparin. The effector molecule through which heparin carries out its action is the serine proteinase inhibitor, antithrombin. This molecule regulates blood clotting by inhibiting the proteinases which carry out this process. Antithrombin is converted from a poor inhibitor of coagulation proteases to a very good inhibitor on binding heparin. This provides a control point for coagulation. The mechanism by which antithrombin is converted to a very good inhibitor of coagulation proteases involves a large change in the structure of this protein. These changes in structure are linked to the changes which occur when antithrombin becomes inactive through the process of polymerisation. Certain patients with thrombosis have been found to have changes in both the stability and heparin affinity of their antithrombin molecules, which forms the underlying basis for the disease. We wish to study the reasons for the effects of mutations in the antithrombin variants by making recombinant mutants which mimic the molecules in the thrombotic patients and carrying out detailed, sophisticated molecular analyses of their interaction with heparin and proteases and their stability under various conditions. Additionally we will engineer recombinant mutants of antithrombin which we believe will stabilise the molecule and potentially act as an improved supplement for therapy. This analysis will provide important insights into the functioning of both heparin and antithrombin and thereby significantly improve our understanding of the control of coagulation.Read moreRead less
Understanding The Role Of Endogenous And Pharmacologic Glycosaminoglycans In Preventing Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$516,642.00
Summary
Pre-eclampsia (PE) is a serious pregnancy complication that affects the well being of the mother and baby. There is no cure for PE except for delivery of the baby. This may result in delivery much earlier than expected causing a very premature baby. This study investigates substances in the placenta that may be responsible for causing PE. If we can understand how these substances cause the problem of PE, we may be able to find better ways of treating or preventing it.