Advances in the diagnosis and treatment of thrombotic thrombocytopenic purpura

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic disease caused by ADAMTS13 deficiency. TTP is classified into two types: immune-mediated TTP (iTTP), which is caused by anti-ADAMTS13 autoantibodies, and congenital TTP (cTTP), which is caused by ADAMTS13 gene abnormalities. In iTTP, epitope profiling of anti-ADAMTS13 autoantibodies has advanced, and structural changes in the ADAMTS13 protein have attracted attention as a hallmark of acute disease. The conventional standard assays for ADAMTS13 activity are manual and time-consuming, but a convenient, highly accurate, and fully automated rapid assay was recently developed. For iTTP, the combination of therapeutic plasma exchange and immunosuppressive therapy with caplacizumab, an anti-VWF nanobody, has been shown to prevent early fatal thrombosis and reduce mortality. For cTTP, a phase III clinical trial demonstrated the efficacy and safety of recombinant ADAMTS13, which led to the coverage of this treatment by Japanese national health insurance.