Novel therapies in thrombotic thrombocytopenic purpura

Abstract

Essentials The standard of care for patients with TTP remains daily plasma exchange in addition to immune suppressive therapy.Despite the improved treatment options for TTP, the acute mortality of TTP remains between 15‐20%.Caplacizumab reduces the time to platelet recovery and the exacerbation rate in acute TTP.A better understanding of the cause and treatments of long‐term complications of TTP are needed. Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and a consumptive thrombocytopenia, as a result of severe deficiency of ADAMTS13. The standard of care of the acute episode is treatment with plasma exchange and immunosuppression. After the acute episode is resolved, patients face a significant risk of relapse and long‐term complications associated with significant morbidity and even mortality. Novel treatments have been under development and will be discussed in this review. Caplacizumab, a nanobody that blocks the interaction between VWF and platelets, has shown promising results in decreasing the time to recover from the acute events that will hopefully translate into long‐term clinical benefit for patients. In addition, identifying biomarkers to allow us to better predict the risk for relapse and the development of these long‐term complications in patients with TTP are a few of the challenges that require our attention moving forward.

The role of ADAMTS‐13 and von Willebrand factor in cancer patients: Results from the Vienna Cancer and Thrombosis Study

“…An approach via rADAMTS‐13 would be advantageous, as it cleaves only the highly active forms of the protein, leaving basal levels of VWF in the circulation . For a possible future outlook, in a recent review of therapies for TTP there was also promising data presented for both, rADAMTS‐13, which showed good tolerance in a phase 1 clinical trial, and for caplacizumab which is a nanobody that inhibits ULVWF mediated platelet aggregation under high shear rates, therefore theoretically also not interfering with basal VWF function.…”

Molecular suitability of the chacma baboon in human‐targeted Von Willebrand factor directed studies

“…23 However, with conflicting clinical results, it is still considered worthwhile to explore NAC as a possible treatment option in TTP. 37 The ADAMTS13 cleavage site (Tyr1605-Met1606) is also still intact in the chacma baboon sequence. Therefore, future research considering the use of recombinant ADAMTS13 or any other agent that specifically targets this region may find the pre-clinical chacma baboon model of acquired TTP a reliable and accurate prediction model.…”

Emerging roles of adjunct therapies in acquired thrombotic thrombocytopenia purpura

“…Rituximab was initially administered as adjunct therapy in refractory aTTP patients who had failed TPE and steroids. These refractory patients had shorter time to remission and reduction in relapse rates when compared to historical cohorts receiving TPE with adjunct steroids or other drugs . Its use as an upfront therapy has also been investigated.…”

“…Anfibatide, a snake venom‐derived platelet GP1b receptor antagonist, also inhibits vWF‐platelet interaction. Clinical trials have thus far been limited to myocardial infarction patients, but in murine TTP models, platelet aggregation was inhibited . N‐acetylcysteine (NAC) targets vWF similarly to its action on mucin, by cleaving disulfide bonds within ultra‐large vWF multimers to reduce vWF size.…”