Project Title

Characterisation of anti-ADAMTS13 Antibodies in Thrombotic Thrombocytopenic Purpura.

Project Summary

ADAMTS13 is an anti-coagulant protein that cleaves the von Willebrand Factor (vWF), a process that is important in the maintenance of haemostasis. When ADAMTS13 deficiencies occur, ultra large vWF multimers persist in the blood circulation, leading to the formation of small blood clots (microthrombi) – this results in thrombotic thrombocytopenic purpura (TTP), a condition that is fatal if left untreated. Deficiencies in ADAMTS13 can result from inactivating mutations in ADAMTS13, or from the presence of neutralising autoantibodies directed against ADAMTS13.

There are indications of anti-ADAMTS13 antibodies which are non-neutralising, demonstrated by individuals with high titres of ADAMTS13 autoantibodies that do not develop TTP.

Current anti-ADAMTS13 autoantibody detection methods do not discriminate between the neutralising and non-neutralising forms, manifesting in high false-positives and a lack of specificity against targeted ADAMTS13 epitopes. ADAMTS13 levels are key to the correct and accurate diagnosis of TTP, and differentiation from other TMAs such as aHUS.  Equivocal samples between 8-20% remains challenging and has significant impacts on real world implications.

This study aims to develop a method for screening patient samples for specific populations of anti-ADAMTS13 autoantibodies and determining their role in thrombotic disorders, including TTP onset and stroke.

Blood Disorder

• Thrombotic Microangiopathy (blood clots in the small vessels)

Patient Recruitment Details

Patient recruitment status: Open

Patients are required to provide a 40mL blood sample, collected by a fully trained phlebotomist or a medical practitioner. The sample will be stored and used for testing for ADAMTS13 activity and antibody level, other biomarkers for TTP and DNA/RNA extracted for genetic analysis. An additional 10mL of venous blood will be collected for further analysis if the platelet count returns to normal prior to day 30, at day 30 and day 90, 180 and day 360. Patients will then be followed for a period of 3 years for clinical and laboratory evidence of relapse.

Patients can access collection centres from sites in Australia, New Zealand, Singapore, Malaysia, South Korea, Thailand, Hong Kong and China.

Number of Patients

300 patients with TTP over a 5-year period (2016-2021).

Coordinating Centre and Central Laboratory

• PBI Research Division
• Murdoch University

Supporting Organisations

• Thrombosis and Haemostasis Society of Australia and New Zealand
• Asia Pacific Society on Thrombosis and Haemostasis