Journal Article

Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura

Foy, Brody H., Stefely, Jonathan A., Carney, Brian J., Bendapudi, Pavan K., Feingold, Louis M., Friedman, Kenneth D., Park, Doyun, Ruby, Kristen N., Leaf, Rebecca K., Lau, Emily S., Stone, James R., Tatake, Ishan, Hassan, Sajjad, Wilkinson, Shelby C., Brunker, Patricia A.R., Liu, Jun, Cruz, Wendy, Burke, Kristen E., Avelino, Alzira R., Chen, Maria Y., Dzik, Walter H., Makar, Robert S., Mueller, Sarah B., Andrzejewski, Chester, Higgins, John, Goldberg, Rachel L.

2024

Overview

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP. In a 28-year-old woman with postpartum immune thrombotic thrombocytopenic purpura, plasma exchange was unsuccessful. Near death while receiving vasopressors, she was treated with recombinant ADAMTS13, and the disease abated.

• Publisher: Massachusetts Medical Society
• Subject: ADAMTS13 Protein - immunology / ADAMTS13 Protein - therapeutic use / Adult / Allergy / Antigen-Antibody Complex - blood / Antigen-Antibody Complex - immunology / Apheresis / Autoantibodies / Autoantibodies - blood / Autoantibodies - immunology / Autoimmune Disease / Black or African American / Blood platelets / Cloning / Coagulation / Collaboration / Dehydrogenases / Drug dosages / Female / Hematology / Humans / Immune clearance / Immunology / Laboratories / Metalloproteinase / Microvasculature / Oncology / Patients / Plasma / Plasma Exchange / Purpura / Purpura, Thrombotic Thrombocytopenic - diagnosis / Purpura, Thrombotic Thrombocytopenic - drug therapy / Purpura, Thrombotic Thrombocytopenic - immunology / Purpura, Thrombotic Thrombocytopenic - therapy / Recombinant Proteins - immunology / Recombinant Proteins - therapeutic use / Thrombocytopenia / Thrombocytopenic purpura / Thrombosis / Thrombotic thrombocytopenic purpura / Treatment Outcome / Vagina