Management of thrombotic thrombocytopenic purpura

Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of >80%. However, relapses occur in up to 40% of patients and refractory disease with fatal outcomes still occurs, typically within the first days of management. In this context, the introduction of rituximab has been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, and increasingly as frontline therapy, with high response rates in the following weeks. In more severe patients, salvage strategies typically include twice daily TPE, pulses of cyclophosphamide, as well as splenectomy in the more desperate cases. In this life-threatening and debilitating disease, relapses can be efficiently prevented in patients with a severe acquired ADAMTS13 deficiency and otherwise in remission with the use of rituximab. In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, international, clinical trials. Promising agents under evaluation include caplacizumab (an inhibitor of the glycoprotein-Ib/IX-Von-Willebrand factor axis), N-acetylcysteine, recombinant ADAMTS13, and anti-plasmocyte compounds.