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. In this context, the introduction of rituximab 
has probably 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, or even as frontline therapy, with high 
response rates. In more severe patients, salvage strategies may include twice 
daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in 
the more desperate cases. In this life-threatening 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, 
ideally international, clinical trials. Promising agents under evaluation 
include N-acetylcysteine, bortezomib, recombinant ADAMTS13 and caplacizumab, an 
inhibitor of the glycoprotein-Ib/IX-von Willebrand factor axis.