Immune thrombotic thrombocytopenic purpura: Personalized therapy using ADAMTS‐13 activity and autoantibodies

Abstract

Essentials• An expert group has advised ADAMTS-13 blood tests in immune-mediated thrombotic thrombocytopenic purpura (ITTP).• We used ADAMTS-13 monitoring to guide treatment in three patients with ITTP.• This approach allowed cautious stopping of caplacizumab and less rituximab use.• This new treatment approach may be helpful to others.

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

“…Several therapeutic targets have been proposed to restore homeostatic balance at this level. They include replacement therapies consisting in infusions of plasma or recombinant ADAMTS13, indicated for congenital deficiencies (currently at the phase 3 clinical stage) [ 334 ], or the administration of immunomodulators, such as prednisone or rituximab, if the origin of the disorder is autoimmune [ 335 ]. In addition, immunotherapy can be administered through anti-vWF monoclonal antibodies, such as caplacizumab [ 335 ], a bivalent humanized agent that acts on vWF’s A1 domain, inhibiting its interaction with platelets and preventing high-molecular-weight vWF monomer-mediated platelet adhesion.…”

“…They include replacement therapies consisting in infusions of plasma or recombinant ADAMTS13, indicated for congenital deficiencies (currently at the phase 3 clinical stage) [ 334 ], or the administration of immunomodulators, such as prednisone or rituximab, if the origin of the disorder is autoimmune [ 335 ]. In addition, immunotherapy can be administered through anti-vWF monoclonal antibodies, such as caplacizumab [ 335 ], a bivalent humanized agent that acts on vWF’s A1 domain, inhibiting its interaction with platelets and preventing high-molecular-weight vWF monomer-mediated platelet adhesion. This strategy attenuates the availability of vWF, which, in turn, leads to transient reductions in the total concentration of the vWF antigen and to a concomitant decrease in FVIII levels during treatment.…”