Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare but life-threatening disease caused by an autoantibody-mediated mechanism of deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13. Novel therapeutic principles have challenged the standard of care, consisting of therapeutic plasma exchange (TPE), glucocorticoids, and adjunct immunosuppressants. Anti-VWF therapy with caplacizumab has been shown to be effective in halting thrombotic microangiopathy earlier, preventing early relapses, and potentially lowering TTP-associated mortality. It has also opened avenues toward a more tailored treatment approach guided by ADAMTS13 activity levels and a treatment algorithm forgoing TPE. This article highlights the importance of an early diagnosis and early therapeutic interventions indiscriminate of the initial clinical presentation that ultimately enable a TPE-free treatment. Moreover, it discusses the approach to handling immunosuppression and anti-VWF therapy in cases with prolonged autoimmunity. Timely diagnosis and therapy are based on on-site ADAMTS13 testing and the immediate availability of anti-VWF therapy in an emergency situation while close monitoring of the clinical and laboratory response to anti-VWF-therapy informs the decision to forgo TPE. A novel standard of care comprising anti-VWF-therapy, glucocorticoids, and early immunosuppression with anti-CD20-agents with or without TPE in selected cases based on cases series and the MAYARI trial (NCT05468320) is currently being established.
Paul Brinkkötter (Fri,) studied this question.