Thrombotic thrombocytopenic purpura: celebrating 25 years of ADAMTS13

Thrombotic Thrombocytopenic Purpura (TTP) was first described just over a century ago and it is now 25 years since the identification of ADAMTS13 as the enzyme deficient in both antibody-mediated immune TTP and congenital TTP. The discovery of ADAMTS13 has been fundamental to the vast improvement seen in TTP outcomes. Understanding the interaction between ADAMTS13, platelets and vWF led to development of clinical ADAMTS13 assays and therefore quicker and accurate diagnosis, but also, critically, to novel therapies and monitoring of treatment. Landmark additions to immune TTP therapy have included anti-CD20 treatment with rituximab, in both the acute and elective setting and the use of the nanobody caplacizumab in acute TTP. In congenital TTP, the use of ADAMTS13 replacement is playing a role in reducing end-organ damage and morbidity, with recombinant ADAMTS13 now representing the gold standard for cTTP. The ability to measure response to treatment by monitoring ADAMTS13 activity has underpinned these treatment advances and allowed clinicians to tailor immunosuppressive treatment for iTTP and rADAMTS13 dosing in cTTP. Looking forward, there are many avenues for future development with potential expansion of recombinant ADAMTS13 to treat immune TTP, new, quicker assays to improve diagnosis, monitoring and immunomodulatory therapeutic advancement, all underpinned by ADAMTS13. Future endeavors for the role of ADAMTS13 in other thrombotic indications opens further exciting opportunities.