University of Tasmania, Australia

Description

Research Overview

Thrombosis ("blood clots") and associated manifestations such as atherosclerosis are leading causes of morbidity and mortality in developed countries and are complications that develop in a wide range of diseases, including cancer, chronic kidney disease, diabetes, stroke and autoimmune diseases such as systemic lupus erythromatosus (SLE) and the anti-phospholipid syndrome (APS). With an aging population both in Tasmania and Australia, the costs associated with the diagnosis and treatment of thrombosis are forecast to provide a significant financial burden on the healthcare system.

Our research investigates aspects of haemostasis i.e., blood coagulation, fibrinolysis and platelet function, to identify abnormalities that potentially contribute to thrombosis.

Although our laboratory is involved in a range of haemostasis based projects, we are particularly interested in abnormalities of blood coagulation. This pathway is initiated by the exposure of tissue factor (TF) to the circulating blood leading to the generation of fibrin, which helps to stabilize the platelet plug to form a blood clot. The natural inhibitor of TF is tissue factor pathway inhibitor (TFPI), which regulates the initiation of coagulation by inhibiting TF - activated factor VII (TF - FVIIa) in the presence of activated factor X (FXa). To date, no direct relationship between low levels of TFPI and thrombosis has been described, although animal models of disseminated intravascular coagulation and gene knockout experiments in mice support an essential physiological role for TFPI in preventing thrombosis.

In some SLE and APS patients we have demonstrated that the ability of TFPI to effectively regulate blood coagulation is compromised and may contribute to ongoing thrombotic episodes. Research is ongoing to determine the precise mechanism(s) that cause impaired regulation of blood coagulation. This work could potentially lead to the development of new diagnostics and therapeutics, and ultimately improved care of patients with SLE, APS and other thrombotic diseases.

Collaborators

Methods

The haematology and research laboratories are well resourced to conduct a variety of techniques, including affinity chromatography, flow cytometry, amidolytic activity assays, thrombin generation assays, cell culture, routine haematology and coagulation testing, plasma and whole blood platelet aggregation, SDS-PAGE, Western Blotting, immunofluorescence and ELISA.

Funding

Research is currently supported by the University of Tasmania and Clifford Craig Medical Research Trust.

Link to Publications and Current Projects (via WARP): (http://rmdb.research.utas.edu.au/public/rmdb?indiv_detail_warp_trans+20036)

Research students and associated projects (at the University of Tasmania)

Contact

For further information on current and/or future projects, please contact Dr Murray Adams (email: Murray.Adams@utas.edu.au, or phone: +61 3 6324 5483).

Selected Publications:

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• Adams MJ. Novel Considerations in the Pathogenesis of the Antiphospholipid Syndrome: Involvement of the Tissue Factor Pathway of Blood Coagulation. Seminars in Thrombosis and Hemostasis. 34, 251-255. 2008.
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• Ahuja KDK, Adams MJ, Robertson I and Ball MJ. Acute effect of a high-carbohydrate low-fat meal on platelet aggregation. Platelets, 20, 606-609. 2009.
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• Adams MJ, Ahuja KDK and Geraghty DP. Effect of Capsaicin and Dihydrocapsaicin on in vitro Blood Coagulation and Platelet Aggregation. Thrombosis Research. 124, 721-723. 2009.
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• Palatinus, AA and Adams MJ. Thrombosis in Systemic Lupus Erythematosus. Seminars in Thrombosis and Hemostasis. 35, 621-629. 2009.
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• Adams MJ, Palatinus AA, Harvey AM, and Khalafallah AA. Impaired control of the tissue factor pathway of blood coagulation in systemic lupus erythematosus. Lupus. 20, 1476 – 1485, 2011.
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• Palatinus AA, Ahuja KDK, and Adams MJ. Effect of APL on in vitro platelet aggregation. Clinical and Applied Thrombosis and Hemostasis. 18, 60 – 66, 2012.
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• Adams MJ. Tissue factor pathway inhibitor: New insights into an old inhibitor. Seminars in Thrombosis and Hemostasis. Seminars in Thrombosis and Hemostasis. 38, 129 – 134, 2012.