How I treat refractory thrombotic thrombocytopenic purpura

purpura (TTP) is characterized by throm-bocytopenia andmicroangiopathic hemo-lytic anemia (MAHA) without an obvious cause, and may include fever, mild re-nal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metallopro-teinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer envi-ronment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on thepresenceof clinical symptoms, lab-oratory aberrations consistent withMAHA, decreased ADAMTS13 activity, and pos-sibly presence of anti-ADAMTS13 autoan-tibodies. Upfront treatment of acute TTP includes plasma exchange and cortico-steroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the man-agement of the refractory TTP patient. Management involves simultaneously rul-ing out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, in-creased plasma exchange, splenectomy, and immunosuppressive options, includ-ing cyclophosphamide, vincristine, and cyclosporine. We also review recent evi-dence for thepotential rolesofbortezomib andN-acetylcysteine, and explore new ther-apeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. (Blood