Acute Traumatic Coagulopathy- Mechanisms And Measurement
Funder
National Health and Medical Research Council
Funding Amount
$188,226.00
Summary
Acute traumatic coagulopathy (ATC) refers to impaired blood clotting post major trauma and is associated with high, early mortality. Inability to predict this disorder and poor knowledge regarding its detailed biochemical mechanism has hindered development of evidence based guidelines to manage patients with ATC. This project aims to correlate early biochemical disorders with clinical management and outcomes post trauma to determine mechanisms leading to ATC and determine management strategies.
A Novel Point Of Care (PoC) Device For Predicting And Monitoring Bleeding And Clotting (haemostasis)
Funder
National Health and Medical Research Council
Funding Amount
$608,979.00
Summary
Manipulating the bleeding/clotting system is a critical but expensive part of modern medicine, eg some people need blood thinners while others can bleed too much. Thrombin generation is the ideal overall test for the bleeding/clotting of blood, but current methods have major problems. We developed and patented a test that deals with most of the problems. This proposal will create an assay that is easy for doctors to perform without a specialised laboratory.
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
A Randomised Controlled Trial Of Factor Replacement Therapy In Snake Bite Coagulopathy
Funder
National Health and Medical Research Council
Funding Amount
$715,730.00
Summary
This proposal seeks funding to undertake a controlled trial of clotting factor replacement in snake bite coagulopathy after the administration of a neutralising dose of antivenom. The aim is to determine if factor replacement will result in a rapid return of clotting function in patients and therefore reduce the potential risk of major bleeding. This study will have international implications because globally snakebite coagulopathy is a major cause of morbidity and death like in Australia.
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.
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.
Too few blood platelets leads to fatal haemorrhage, and patients with low platelet counts require transfusions to prevent bleeding. We have recently discovered the key to keeping platelets alive, and now propose the critical experiments which will teach us how to manipulate it and allow platelets to live longer. Our team leads the world in this field. If successful we expect to improve blood bank platelet storage, and boost the supply of platelets available to patients in need of transfusion.