Taking Empiricism out of Immune Thrombotic Thrombocytopenic Purpura: Current and Future Treatment Strategies

Marshall A. Mazepa, Yara A. Park, Jay S. Raval

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing, humorally-mediated autoimmune disorder characterized by unpredictable episodes of microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with neurologic dysfunction, kidney injury, and fever. Episodes are caused by immune destruction or inhibition of the von Willebrand Factor (vWF) cleaving protease ADAMTS13. Currently, the standard of care is therapeutic plasma exchange (TPE), and most add immunosuppression with corticosteroids - a standard that is unchanged for nearly 30 years. There are multiple strategies for adding corticosteroids to TPE and the limited data available suggests that corticosteroids reduce the duration of ADAMTS13 deficiency in iTTP. Rituximab is also frequently used in the treatment of iTTP and evidence suggests that while it may not reduce the number TPE procedures required to induce remission, it likely increases relapse-free survival. Novel approaches to immunosuppression that have been reported include low-dose rituximab (also currently in clinical trials) and proteasome inhibition. A more targeted approach includes the anti-vWF nanobody, caplacizumab, recently approved for iTTP in Europe and United States, which in two large randomized controlled trials significantly shortened the time to normalization of platelet count, appreciably lowered the 30-day recurrence rate, and decreased the rate of the composite endpoint of death, recurrence, and major thromboembolic events. Recombinant ADAMTS13 has been tested in congenital TTP and could be tested in iTTP as well, along with novel approaches of modifying the enzyme to avoid the immune response or leveraging other vWF cleaving proteases such as plasmin to bypass ADAMTS13. Also, therapies that target preformed antibodies that are currently being tested in other humorally-mediated disorders could cross over to iTTP. Finally, progress has long been hampered in iTTP due to difficulty with accrual and disagreement about trial design. A good surrogate endpoint for relapse-free survival is also needed. Despite these challenges, a new era of precision medicine is likely soon emerging for treatment of iTTP, and with it comes the opportunity to further improve outcomes in this rare and deadly disease.

Original languageEnglish (US)
Pages (from-to)248-255
Number of pages8
JournalTransfusion Medicine Reviews
Volume33
Issue number4
DOIs
StatePublished - Oct 2019

Keywords

  • Immunosuppression
  • Precision medicine
  • Prophylaxis
  • Targeted therapy

PubMed: MeSH publication types

  • Journal Article
  • Review

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