Management of TTP – the main options for diagnosis

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by severe deficiency of ADAMTS13, a von Willebrand factor (VWF)-specific protease. TTP is a severe condition and a medical emergency in hematology. Prolonged time from presentation to diagnosis and therapeutic actions is life-threatening. Establishing a clear diagnosis of TTP is essential, as the therapeutic measures for TTP may include invasive procedures that have risks of their own. Therefore, the discovering and production of a synthetic ADAMTS13-specific VWF fragment (VWF73) allowed for quantification of ADAMTS13 activity, the basis for TTP diagnosis. Further advances led to the development of faster and reliable technologies. One of these widely used methods is fluorescence resonance energy transfer (FRET). Recently, several rapid ADAMTS13 activity assays have become available to potentially fill this void. One is a semi-quantitative screening assay from Technoclone, and the other is a fully automated, quantitative chemiluminescence- based immunoassay (CLIA; HemosIL AcuStar ADAMTS13 Activity, Instrumentation Laboratory, Bedford, MA). The ELISA based activity assay, manufactured by Technoclone (Vienna, Austria) and named Technozym ADAMTS-13 Activity, is the most widely used according to ECAT data. The ELISA based Antigen assay is also possible. Further advances in diagnostic methods led to identifying immune-mediated TTP (iTTP) via the presence of anti- ADAMTS13 immunoglobulin G (IgG) autoantibodies. Methodologies used include enzyme-linked immunosorbent assays (ELISAs) and/or functional inhibitor assays based on mixing studies. The most common approach here is the assessment for functional inhibitors (ie, autoantibodies that block ADAMTS13 activity) using a Bethesda-like assay