Thrombotic thrombocytopenic purpura: a diagnostic and therapeutic challenge.

With the discovery of the ultra-large von Willebrand factor (vWF) in the plasma of thrombotic thrombocytopenic purpura (TTP) patients and the pivotal role played by the ADAMTS13 metalloproteinase, many new challenges are facing both the researcher and the clinician for the diagnosis and treatment of this condition. As a result of these new discoveries, the range of disorders manifesting with many of the clinical features of the disease can now be reclassified into the idiopathic TTP, congenital TTP, and non-idiopathic TTP, based on the level of ADAMTS13 activity. The latter group includes drug-associated TTP. In this article, the background of the pathogenesis, and diagnostic and therapeutic approaches are reviewed. An emerging concept of the pathogenesis of TTP is presented. The merits of various diagnostic procedures including the assay of the ADAMTS13 activity and the immunoglobulin G inhibitory antibodies are discussed. Regarding the therapeutic aspect, although plasma exchange remains the mainstay, the question of addition of immunosuppressive agents comes up, especially in those patients who are refractory to plasma exchange and those that repeatedly relapse. A call for clinical trials to address the question of efficacy of various agents is made.