Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic micro-angiopathy characterized by a microangiopathic hemolytic anemia, severe thrombocytopenia and organ ischemia linked to disseminated microvascular platelet rich-thrombi. TTP is specifically related to a severe deficiency in ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats, member 13), the specific von Willebrand factor-cleaving pro-tease. ADAMTS13 deficiency is most frequently acquired via ADAMTS13 autoantibodies but rarely, it is inherited via mutations of ADAMTS13 gene. The first acute episode of TTP usually occurs during adulthood with a predominant anti-ADAMTS13 autoimmune etiology. In rare cases however, TTP begins as soon as childhood with frequent inherited forms. TTP is ~2 fold more frequent in women and its outcome is characterized by a relapsing tendency. Rapid recognition of TTP is crucial in order to initiate appropriate treatment. The first-line therapy for acute TTP is based on daily therapeutic plasma exchange supplying deficient ADAMTS13, with or without steroids. Additional immune-modulators targeting ADAMTS13 autoantibodies, are mainly based on steroids and the humanized anti-CD20 monoclonal antibody rituximab. In refractory or unresponsive TTP, more intensive therapies including twice-daily plasma exchange, pulses of cyclophosphamide, vincristine, cyclosporine A or salvage splenectomy are considered. New drugs including N-acetylcysteine, bortezomib, recombinant ADAMTS13, and caplacizumab show promise in the management of TTP. Also, long-term follow-up of TTP patients is crucial to identify the occurrence of other autoimmune diseases, to control relapses and to evaluate psychophysical sequelae. Further development of both patients' registries worldwide and innovative drugs is still needed to improve TTP management.
- Submitted October 7, 2016.
- Accepted December 4, 2016.
- Copyright © 2017 American Society of Hematology
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