ADAMTS-13 is a circulating enzyme, which specifically cleaves the ultra large multimeric von Willebrand factor (vWF) and regulates shear dependent platelet glycoprotein Ib mediated thrombus growth and blood vessel occlusion. Deficiency of ADAMTS13 is increasingly being recognized as a common cause of microangiopathic thrombocytopenia (MAT) and in particular the positive diagnosis of thrombotic thrombocytopenic purpura (TTP). ADAMTS-13 testing is now the cornerstone in the diagnosis and treatment of patients with life threatening thrombotic microangiopathy and thrombocytopenia. A large number of ADAMTS-13 activities, antigen and antibody tests are available using different methodologies and platforms. The result of an ADAMTS-13 activity and antibody test will define a diagnosis of TTP (<10% activity) or aHUS (>10% activity) decide whether the TTP is immune mediated (iTTP) or congenital (cTTP), guide therapeutic decisions of plasma exchange, immunomodulation, complement inhibition, VWF blocking, ADAMTS-13 replacement or splenectomy. ADAMTS-13 testing may be useful to monitoring the duration and success of therapy and TTP relapse risk. Molecular testing for ADAMTS-13 and complement pathway mutations can provide further diagnostic information but the widespread use and access is limited.
For these reasons access to reliable and readily available ADAMTS-13 testing is crucial.
In order to address this unmet need, we examined the reliability and clinical interpretation of ADAMTS-13 testing across a large Asia Pacific (AP) population cohort of 3.2 billion people. The 1stAP Microangiopathic Thrombocytopenia Network (APMAT) standardisation of ADAMTS-13 activity and antibody testing project was established and conducted in 24 centres from 10 AP countries. After training and hands on wet workshop, lyophilised samples were sent in 2 surveys using the same platform (chromogenic activity and ELISA antibody assays) and compared with the same samples used in the ECAT QA program. Overall the performance and CV’s were similar to the ECAT QA program and the implementation between laboratories were acceptable with appropriate z scores for inter and intra laboratory measurement.
However precision and clinical interpretation of the ADAMTS-13 activity assay around the 10% cut off level is still problematic that will lead to variation in clinical decisions and management. Interpreting anti ADAMTS-13 antibody assay is even more difficult because the definition between normal and abnormal titres is unclear leading to misdiagnoses of a pathological antibody affecting ADAMTS-13 function. Further work is required to standardise ADAMTS-13 testing for the different clinical situations of the new MAT diagnosis, whether it is iTTP or cTTP, TTP monitoring and prediction of relapse.