Immunotherapy for thrombotic thrombocytopenic purpura

This review focuses on recent advances in the use of immune-based therapy to treat patients with refractory and relapsing acquired thrombotic thrombocytopenic purpura.

Advances in understanding of the pathophysiology of idiopathic thrombotic thrombocytopenic purpura have provided the rationale for immune-based treatment approaches to refractory and relapsing cases of thrombotic thrombocytopenic purpura. The demonstration that a severe deficiency of von Willebrand factor-cleaving protease activity in acquired thrombotic thrombocytopenic purpura is due to an autoantibody inhibitor of the von Willebrand factor-cleaving protease argues for targeting the antibody inhibitor of the von Willebrand factor-cleaving protease with immunosuppressive therapy as a means of increasing protease activity and inducing a sustained remission of the disease. Recent publications, largely case reports and small series of patients, have suggested a role for rituximab and cyclosporine in cases refractory to plasma exchange or resistant to the tapering of plasma exchange therapy.

In the future, a better understanding of the relation between the von Willebrand factor-cleaving protease activity, the nature and titer of von Willebrand factor-cleaving protease inhibitors, and the risk of relapse of thrombotic thrombocytopenic purpura will be important to further validate the strategy of targeting the von Willebrand factor-cleaving protease inhibitory antibody as an effective means of treating acquired thrombotic thrombocytopenic purpura. Prospective data from carefully designed clinical trials are needed to define the effectiveness of specific immunosuppressive therapies at suppressing antibody inhibitors of von Willebrand factor-cleaving protease, improving von Willebrand factor-cleaving protease activity, and inducing a sustained remission of the disease.