Inhibitory anti-ADAMTS 13 antibodies: Measurement and clinical application

SummaryThrombotic thrombocytopenic purpura is an acute life threatening disorder, characterised by thrombocytopenia, microangiopathic haemolytic anaemia and multi organ microvascular thrombi that results in variable clinical symptoms. Just over a decade ago, the missing enzyme required for von Willebrand cleavage was recognised in TTP patients, subsequently identified as ADAMTS 13. Assays have confirmed that the majority of TTP cases are idiopathic and are associated with inhibitors and or IgG antibodies to ADAMTS 13. Such cases take longer to treat and are more likely to relapse. Evidence to date suggests the majority of antibodies block the spacer domain of ADAMTS 13. There may be other antibodies binding to ADAMTS 13 domains but their overall clinical involvement remains to be determined. Immunosuppressive treatments have until now been unsatisfactory. However, monoclonal anti-CD 20 therapy, acting on B-lymphocytes involved in antibody production results in remission in most patients and prevention of recurrent relapse. Further investigation into the antibodies produced in TTP and other aspects of immune dysfunction, such as T cells will further our understanding of this devastating disorder.