Emerging roles of adjunct therapies in acquired thrombotic thrombocytopenia purpura.

Overview

Acquired thrombotic thrombocytopenia purpura (aTTP) is caused by autoantibody-mediated severe deficiency of the von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), with subsequent accumulation of ultra-large vWF-multimers that spontaneously form platelet-VWF complexes and microthrombi within the microcirculation. Therapeutic plasma exchange (TPE), by removing autoantibodies and excess ultra-large vWF multimers and replenishing ADAMTS13 activity, remains the urgent primary initial treatment. Although heterogeneity in treatment exists, most centers add upfront immunosuppression with steroids, and many also add upfront rituximab. Refractoriness, exacerbation and relapse are commonly treated with adjunct rituximab. Despite adjunct steroids and rituximab, TTP refractoriness, exacerbation, relapse, morbidity, and mortality remain problematic. Newer adjunct therapies include suppression of ADAMTS13 autoantibody production via plasma cell depletion, inhibition of vWF-platelet interaction, and replenishment of ADAMTS13 function with recombinant ADAMTS13 protein.