Thrombotic Thrombocytopenic Purpura: Beyond Empiricism and Plasma Exchange

For many years after its first description in 1924, thrombotic thrombocytopenic purpura was an intriguing puzzle for clinicians and researchers, not only for its unique pathology, perplexing changes in von Willebrand factor multimers, and high rate of rapid fatality but also for its dramatic response to plasma infusion or exchange. The discovery of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats member-13) and its deficiency in patients with thrombotic thrombocytopenic purpura, due to inhibitory autoantibodies or genetic mutations, provides a mechanistic scheme for understanding its pathogenesis. This new knowledge quickly led to the use of rituximab to promote its remission and prevent recurrence. Recombinant ADAMTS13 is also under development to replace plasma infusion as the therapy for hereditary thrombotic thrombocytopenic purpura. Recently, caplacizumab, a bivalent nanobody targeting the glycoprotein 1b binding epitope of von Willebrand factor A1 domain, was approved as an addition to the current regimen of plasma exchange and immunomodulation for adult patients of acquired thrombotic thrombocytopenic purpura. This review discusses how the new treatment may improve patient outcomes and its potential pitfalls.