Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura

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

doi:10.1056/NEJMoa2402567

Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura

N Engl J Med. 2024 May 9;390(18):1690-1698. doi: 10.1056/NEJMoa2402567.

Authors

Pavan K Bendapudi¹, Brody H Foy¹, Sarah B Mueller¹, Jun Liu¹, Louis M Feingold¹, Kristen E Burke¹, Wendy Cruz¹, Maria Y Chen¹, Emily S Lau¹, Rachel L Goldberg¹, Ishan Tatake¹, Shelby C Wilkinson¹, Brian J Carney¹, James R Stone¹, Doyun Park¹, Alzira R Avelino¹, Sajjad Hassan¹, Chester Andrzejewski¹, Kristen N Ruby¹, Kenneth D Friedman¹, Patricia A R Brunker¹, Rebecca K Leaf¹, John Higgins¹, Walter H Dzik¹, Jonathan A Stefely¹, Robert S Makar¹

Affiliation

¹ From the Blood Transfusion Service (P.K.B., K.N.R., P.A.R.B., W.H.D., J.A.S., R.S.M.), the Division of Hematology (P.K.B., R.K.L., W.H.D.), the Department of Pathology (B.H.F., J.L., M.Y.C., J.R.S., J.H.), and the Division of Cardiology (E.S.L., R.L.G.), Massachusetts General Hospital, the Division of Hemostasis and Thrombosis (P.K.B., L.M.F., K.E.B., I.T., S.C.W.) and the Division of Hematology and Apheresis Service (B.J.C.), Beth Israel Deaconess Medical Center, and Harvard Medical School (P.K.B., J.L., M.Y.C., E.S.L., R.L.G., I.T., S.C.W., B.J.C., J.R.S., K.N.R., P.A.R.B., R.K.L., J.H., W.H.D., J.A.S., R.S.M.), Boston, the Broad Institute of MIT and Harvard, Cambridge (P.K.B.), the Division of Hematology and Oncology, Lahey Hospital and Medical Center, Burlington (D.P.), and the Department of Hematology and Clinical Oncology (A.R.A.) and the Department of Pathology, Transfusion/Apheresis Medicine Services (S.H., C.A.), UMass Chan Medical School-Baystate Health, Springfield - all in Massachusetts; the Department of Laboratory Medicine and Pathology, University of Washington, Seattle (B.H.F.); and Versiti Blood Center of Wisconsin, Milwaukee (S.B.M., W.C., K.D.F.).

PMID: 38718359
DOI: 10.1056/NEJMoa2402567

Abstract

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

ADAMTS13 Protein* / immunology
ADAMTS13 Protein* / therapeutic use
Adult
Antigen-Antibody Complex / blood
Antigen-Antibody Complex / immunology
Autoantibodies / blood
Autoantibodies / immunology
Black or African American
Female
Humans
Plasma Exchange
Purpura, Thrombotic Thrombocytopenic* / diagnosis
Purpura, Thrombotic Thrombocytopenic* / drug therapy
Purpura, Thrombotic Thrombocytopenic* / immunology
Purpura, Thrombotic Thrombocytopenic* / therapy
Recombinant Proteins / immunology
Recombinant Proteins / therapeutic use
Treatment Outcome

Substances

ADAMTS13 protein, human

Grants and funding

1R01HL166246/HL/NHLBI NIH HHS/United States