Plasma exchange-free therapeutic management of immune-mediated thrombotic thrombocytopenic purpura

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic disorder. Immune-mediated TTP is caused by autoantibodies against ADAMTS13, an enzyme responsible for cleaving von Willebrand factor (VWF). Therapeutic plasma exchange (TPE) combined with corticosteroids has historically been the standard treatment, and has significantly improved patient survival. Caplacizumab, a nanobody targeting the VWF A1 domain, inhibits platelet-VWF interactions. Addition of caplacizumab to standard therapy has led to rapid platelet count recovery and prevention of thrombotic events in acute phases. Caplacizumab combined with immunosuppressive therapy has been effective in patients unable to undergo TPE due to clinical or logistical challenges, such as anaphylaxis to fresh frozen plasma or religious restrictions. A retrospective study in 2024 reported that 90.5% of patients achieved clinical response without TPE, highlighting the potential for plasma exchange-free management of acute immune-mediated TTP. These findings underscore the growing importance of caplacizumab in modern TTP therapy. Currently, a phase 3 clinical trial (MAYARI) is evaluating the efficacy of caplacizumab and immunosuppressive therapy without TPE in treating acute immune-mediated TTP. This trial aims to validate a simplified treatment paradigm, potentially transforming the management of TTP by offering safe and effective alternatives to TPE.