Targeting the pathophysiology of TTP. Anti-CD20 agents, such as rituximab, kill B cells and prevent their differentiation into plasma cells. Long-lived plasma cells may be targeted by agents with activity against multiple myeloma, such as bortezomib. Anti-ADAMTS13 autoantibodies are removed by plasma exchange. ADAMTS13 can be replaced by plasma exchange and potentially by recombinant ADAMTS13 (indicated by triangles marked with “r”). Large thrombogenic VWF multimers can be shortened by reducing agents like N-acetylcysteine. The thiol (SH) of N-acetylcysteine attacks and cleaves disulfide bonds of VWF, making smaller VWF multimers disulfide-linked (S) to the cysteine moiety. Inhibitors of VWF-platelet interactions, such as caplacizumab, can stop the progression of TTP in the absence of ADAMTS13.