About us

What is the TMA Registry?

The TMA Registry systematically collects data on patient management and outcomes across different institutions in Australia and New Zealand for patients diagnosed with TTP, aHUS or HUS.

It was established in 2008 by the Department of Epidemiology and Preventive Medicine (DEPM) at the School of Public Health and Preventive Medicine (SPHPM) at Monash University, in collaboration with the Australian Red Cross Blood Service and participating hospitals.

Overview

Title

Thrombotic Microangiopathies (TMA) Registry

Formerly known as: Thrombotic Thrombocytopenic Purpura/Thrombotic Microangiopathies Registry (TTP/TMA Registry)

Coordinating organisation

Transfusion Research Unit (TRU), Monash University, Australia

Australian Register of Clinical Registries

ID No. ACSQHC-ARCR-034

Background

Thrombotic Microangiopathies (TMAs) are characterised by platelet aggregation within small blood vessels. This consumes platelets (causing thrombocytopenia), and the damaged/narrowed vessels cause mechanical destruction of red blood cells (microangiopathic haemolytic anaemia). The consequent disruption to blood flow within small vessels leads to end organ damage/dysfunction (e.g. kidney failure or stroke). Thrombotic microangiopathies can occur as a result of a variety of inherited and acquired conditions, and are now seen (and recognised) more commonly, particularly as they can occur as a result of new medications, such as some of the newer anti-cancer agents.

The TMA with the oldest historical accounts is, thrombotic thrombocytopenic purpura (TTP), long recognised as a TMA affecting primarily the central nervous system and kidneys. TTP is a rare, life threatening disorder that had an almost universally fatal outcome till the introduction of plasmapheresis in the late 1980s and early 1990s. Both the disease and its treatment can result in complications, and while early commencement of plasmapheresis-based treatment results in good outcomes for the majority of patients, the mortality rate may has lingered around 10 %. Some survivors have life-long neurological deficit, or renal impairment. Relapses are common, the disease burden for patients and the community is substantial.

Haemolytic Uraemic Syndrome (HUS) is another rare TMA often preceded by a diarrhoeal illness caused by Shiga toxin-producing organisms (especially Escherichia coli (STEC) or Shigella bacteria). This type of HUS is most commonly encountered in children and adolescents, and can occur in clusters or large outbreaks.

The term “Atypical HUS” (aHUS) has been used to encompass a group of TMAs that are neither TTP or HUS, and which are most commonly associated with acquired or inherited defects in the complement pathway or complement regulatory proteins. Even amongst patients with an inherited defect of complement biology, disease expression/manifestation seems to depend on an environmental trigger, though the latter is rarely identified. Historically, aHUS also included a number of conditions due to inherited abnormalities outside of the complement pathway (especially mutations associated with coagulation).

There has been significant progress in our understanding of TMA, supported by a general acceptance that TTP is due to deficient activity in the enzyme ADAMTS13 (hereditary or acquired), identification of many of the mutations in complement and complement regulatory proteins responsible for cases of aHUS, and the emergence of new therapies. Nevertheless, our understanding remains incomplete and it can still be difficult to determine the aetiology/pathophysiology(ies) for individual patients, particularly where more than one aetiological factor is present. These factors make classification of TMA difficult and have given rise to suggestions for new classification, more practically or therapeutically based. The natural history of various TMAs in different clinical settings, including pregnancy remains unknown, and there is an ongoing need to assess the efficacy of new and emerging therapies.

The purpose of the TMA Registry is to collect information on these rare conditions to better understand how frequently they occur, the therapies doctors use to treat the disorders and the complications of the disease and it’s treatment.

Registry Aims

The TMA Registry aims to:

  • Determine the incidence, natural history, specific clinical characteristics, and clinical outcomes of patients with TMAs, particularly TTP, HUS and aHUS
  • Provide information on the range of therapies employed in the treatment of TMA patients
  • Explore factors influencing clinical outcomes
  • Help define optimal management of patients with TTP and HUS
  • Inform and inspire future hypothesis-driven research in this area

Funding

Monash University (in kind)

Collaborating Institutions

Monash University