Novel therapeutic approaches for thrombotic thrombocytopenic purpura

Acquired thrombotic thrombocytopenic purpura is an immune-mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13). Standard treatment with therapeutic plasma exchange and immunosuppression with steroids results in high remission and low mortality rates. However, a number of patients remain refractory to frontline therapy and/or experience multiple relapses. This study reviews emerging therapies for thrombotic thrombocytopenic purpura.

Studies indicate that reducing anti-ADAMTS13 antibody levels through B-cell depletion or proteasome inhibition is effective for the management of refractory disease. Preliminary reports examining anti-CD20 therapy for the treatment of initial disease or as maintenance therapy for seropositive patients suggest the addition of immunosuppression in other disease phases may delay relapse. Exciting developments in targeted therapies to von Willebrand Factor and recombinant ADAMTS13 hold promise for transforming disease management.

Approximately half of patients diagnosed with acquired thrombotic thrombocytopenic purpura experience refractory and/or relapsing disease. For these patients, a hematologic remission may be an insufficient therapeutic goal. With recent developments, it is now possible to envision a multifaceted approach targeting disease mechanisms that may dramatically improve outcomes for this otherwise debilitating disease.