Pathogenesis and novel treatment of thrombotic thrombocytopenic purpura

Abstract

The key clinical symptoms of thrombotic thrombocytopenic purpura (TTP) are severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia/infarction due to microthrombi. Hemolytic anemia in TTP is characterized by mechanical damage to red blood cells. TTP is caused by a severe deficiency of ADAMTS13 activity, which is caused by mutations in the ADAMTS13 gene (congenital TTP) or by autoantibodies affecting the function or clearance of ADAMTS13 (immune TTP). Patients with congenital TTP receive fresh frozen plasma (FFP) transfusion for the supplementation of ADAMTS13. Meanwhile, those with immune TTP receive plasma exchange therapy using FFP for the supplementation of ADAMTS13 and the removal of anti-ADAMTS13 autoantibodies. Corticosteroid therapy is concurrently administered to suppress autoantibody production. In terms of novel treatment, the use of rituximab, a humanized anti-CD20 monoclonal antibody, in patients with immune TTP was approved by the Japanese health insurance in 2020. Novel and promising drugs are currently developed. A first-in-human study of recombinant ADAMTS13 for congenital TTP was reported in 2017. Caplacizumab is a humanized nanobody that inhibits the interaction between von Willebrand factor and platelets. This drug can prevent early thrombus formation and organ damage in patients with immune TTP. Therefore, these novel drugs can improve mortality in patients with TTP.