Purpose of review: Thrombotic thrombocytopenic purpura, a clinical syndrome characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange therapy in the 1970s. Current outcomes have improved dramatically with the initiation of prompt plasma exchange, a treatment routinely used without any real understanding of why it is effective.
Recent findings: Recent advances suggest that a deficiency of a specific plasma metalloprotease, responsible for the physiological processing of von Willebrand factor multimers, plays a substantial role in the pathogenesis of congenital and acquired idiopathic thrombotic thrombocytopenic purpura. The von Willebrand factor-cleaving protease has now been identified as a new member of the ADAMTS family of metalloproteases, designated ADAMTS13. The acquired form of thrombotic thrombocytopenic purpura is associated with inhibitory autoantibodies against ADAMTS13, and the congenital chronic relapsing form is caused by mutations in the ADAMTS13 gene, resulting in a constitutional deficiency. Plasma exchange has been proved to be the most important therapy in thrombotic thrombocytopenic purpura, but clinical data for adjunctive therapies, such as corticosteroids, antiplatelet drugs and other immunosuppressive agents often used in combination with plasma exchange, are less well defined.
Summary: Recent advances in our understanding of the pathological mechanisms of thrombotic thrombocytopenic purpura not only provide a rationale for the previously empirical plasma exchange therapy (removal of the inhibitory antibodies and replacement of the deficient protease from the plasma infused), but may also help in developing more rational and targeted treatment strategies. This review discusses the clinical presentation, pathophysiology and current management of thrombotic thrombocytopenic purpura.