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Frontiers in pathophysiology and management of thrombotic thrombocytopenic purpura

  • Progress in Hematology
  • Progress in pathophysiology and treatment of thrombocytopenia
  • Published:
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Abstract

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease in which platelet-rich microthrombi cause end-organ ischemia and damage. TTP is caused by markedly reduced ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Hereditary or congenital TTP (cTTP) is caused by ADAMTS13 gene mutations. In acquired or immune TTP (iTTP), ADAMTS13 activity is reduced by anti-ADAMTS13 autoantibodies. TTP is characterized by thrombocytopenia, hemolytic anemia, fever, renal dysfunction, and neuropsychiatric symptoms. Therapeutic plasma exchange (TPE) and immunosuppressive therapy are the mainstays of treatment. As untreated TTP has a high mortality rate, immediate initiation of TPE is recommended when TTP is suspected. Conventionally, corticosteroids have been used for immunosuppressive therapy. Current drug therapies include rituximab, an anti-CD20 antibody that is effective in newly diagnosed cases and refractory cases, as well as for relapse prevention, and caplacizumab, an anti- von Willebrand factor (VWF) nanobody that inhibits the binding of platelets to VWF and prevents microthrombi formation. Recombinant human ADAMTS13 is a promising treatment for cTTP. Although these therapeutic advances have improved the outcomes of TTP, early diagnosis and prompt initiation of appropriate therapy are necessary to achieve these outcomes.

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Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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  1. Department of Blood Transfusion Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Masayuki Kubo & Masanori Matsumoto

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  1. Masayuki Kubo
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  2. Masanori Matsumoto
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MK reviewed the articles on TTP and wrote the manuscript. MM reviewed and edited the manuscript.

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Correspondence to Masanori Matsumoto.

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Conflict of interest

MM is an inventor of the ELISA used to assess ADAMTS13 activity and has received research funds from Chugai Pharmaceutical and lecture fees from Sanofi, Alexion Pharmaceuticals, and Takeda Pharmaceutical. MK has no conflicts of interest.

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Kubo, M., Matsumoto, M. Frontiers in pathophysiology and management of thrombotic thrombocytopenic purpura. Int J Hematol 117, 331–340 (2023). https://doi.org/10.1007/s12185-023-03552-8

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