Thrombotic Thrombocytopenic Purpura (TTP)

TTP is a rare, life-threatening blood disorder and must be diagnosed quickly. The condition can cause strokes, heart attacks, renal failure, pregnancy loss, and produce long lasting disability.

Background information

• Statistics for 2023 show that 1:5 people still die from the disorder.
• Approximately 20 people in Western Australia each year are affected: 200/year throughout Australia.
• TTP is caused by an enzyme deficiency of ADAMTS-13 in the blood.
• A person can be born with an ADAMTS-13 deficiency or acquire it by developing an autoantibody against ADAMTS-13.

ADAMTS-13 is a vital enzyme and when deficiencies occur microthrombi form and results in TTP. Currently, diagnosis is difficult and delayed, with ADAMTS-13 testing not widely available. Results could take up to a week and can be very expensive. One of the key laboratory tests used in diagnosis is measuring the ADAMTS-13 activity.

During the last 10 years, PBI has led the international research community effort for the global standardisation and improvement in the availability of a reliable ADAMTS-13 test.

Presentation of results at the ISTH Congress 2023

In June 2022, Phase 1 of the IMATAS (International Microangiopathic Thrombocytopenia ADAMTS-13 Standardization) study was presented at the ISTH Congress in London. At this year’s congress in Montreal, PBI’s Prof. Ross Baker was joined by Research Scientist, Grace Gilmore from Murdoch University, to present the results of the study.

The aim of the study was to assess international differences and clinical interpretation of ADAMTS-13 testing within the IMATAS network of 16 laboratories from the USA, EU, UK, Switzerland, Japan, Malaysia, Argentina and Australia. The interpretation of an ADAMTS-13 activity level secures the diagnosis of TTP and defines the success of treatment and relapse. If the ADAMTS-13 level is low, ADAMTS-13 antibody assessment will identify the difference between immune-mediated (iTTP) and congenital (cTTP) TTP.

The study found that distinguishing between a low ADAMTS-13 antibody concentration from normal can be problematic. All laboratories found universal consensus for TTP diagnosis, except in those with a borderline level. Therefore, TTP can be diagnosed reliably by ADAMTS-13 activity testing. However, it is a recommendation that the reliance on the examination of ADAMTS-13 antibody measurement to differentiate between iTTP and cTTP requires further standardisation.

Therefore, Phase 2 of this study is to develop an international ADAMTS-13 antibody standard to help standardise antibody testing.

Ceveron s100

The current method for ADAMTS-13 activity testing takes approximately 3.5 hours. Therefore, developing a tool to reduce this would be instrumental in reducing the time and efficacy in diagnosing TTP. Technoclone is a world-leading producer of diagnostic tests, equipment, and research products in haemostasis and fibrinolysis. They have developed the Ceveron s100 coagulation analyser which reduces the testing time to 35 minutes.

PBI have been collaborating with Nikolaus Binder of Technoclone on the IMATAS study to standardise ADAMTS-13 activity testing. We have acquired the new Ceveron s100 at our research lab at Murdoch University to continue the research.

AcuStar

The AcuStar is another specialised testing analyser which has come onto the market. It offers full automation of highly sensitive immunoassays and delivers exceptional accuracy and efficiency. The AcuStar is an instrument developed by Werfen; worldwide leaders in diagnostic testing equipment in the area of haemostasis. Using chemiluminescence (the emission of light as the result of a chemical reaction), it can also do an ADAMTS-13 activity test within 35 minutes. PBI is currently evaluating this method also.

Effective and swift measuring of ADAMTS-13 has not only a huge impact on diagnosis but also monitoring people for early relapse so that pre-emptive treatment can be considered. Visit our website for additional information about TTP.