Table 2.

Novel targeted therapies for TTP

Therapy	Mechanism/target	Supporting evidence
Rituximab	Suppress anti-ADAMTS13 antibody by depleting CD20-positive B cells	Retrospective and prospective studies show benefit in acute TTP and for relapse prevention (Table 1)
Caplacizumab	Nanobody directed toward the A1 domain of VWF inhibits VWF’s interaction with platelet GP1b-IX-V receptors	Phase 2 and 3 trials demonstrated reduced time to platelet normalization, lower exacerbation rates, and reduction in mean PEX procedures and hospital length of stay compared with placebo
NAC	Cleaves VWF multimers by reducing disulfide linkages	Reduction in VWF multimer size and VWF-dependent platelet aggregation in preclinical models
		Case reports of successful use in refractory TTP
Bortezomib	Reduction in anti-ADAMSTS13 antibody production through apoptotic destruction of plasma cells	Case reports and series of successful use in patients refractory to multiple lines of therapy
Recombinant ADAMTS13	Neutralization of anti-ADAMSTS13 antibodies and restoration of ADAMSTS13 activity	Phase 1 trial demonstrated safety in congenital TTP; phase 3 trial planned
Anfibatide	Reduces platelet–VWF interaction through antagonism of the platelet GP1b receptor	Inhibited platelet–VWF aggregate formation in in vitro studies and resolved thrombocytopenia in a mouse model of TTP