PB0313 - Towards The Standardisation Of ADAMTS-13 Antibody Testing In Thrombotic Thrombocytopenic Purpura (TTP)–Results Of The IMATAS Collaborative Study

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Ross Baker, MD

Professor of Haematology
Health Futures Institute, Murdoch University, Perth, Australia
Perth, Western Australia, Australia

Co-Author(s)

JT

Jim Tiao

Senior Research Scientist
Health Futures Institute, Murdoch University, Perth, Australia
Perth, Western Australia, Australia
GG

Grace Gilmore

scientist
Murdoch University
Murdoch, Western Australia, Australia
MM

Masanori Matsumoto

Professor
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
Kashihara, Nara, Japan
Paul Knoebl, MD

Professor
Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
AS

Analia Sánchez-Luceros

MD, Dr.
Laboratorio de Hemostasia y Trombosis IMEX-CONICET-ANM y Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina
Marie Scully, MD

Professor of Haemostasis and Thrombosis
Department of Haematology, University College London Hospitals, London, UK
London, England, United Kingdom
JS

Jameela Sathar

Consultant Haematologist
Department of Hematology, Hospital Ampang, Ampang, Selangor, Malaysia
Ampang, Selangor, Malaysia
AV

Agnès Veyradier

Professor
Service d’Hématologie Biologique, Hôpital Lariboisière, Assistance Publique–Hôpitaux de Paris and EA3518, Institut de Recherche Saint Louis, Université de Paris, Paris
Paris, Ile-de-France, France
IM

Ilaria Mancini, PhD

Post-Doc Research Fellow
Università degli Studi di Milano, Department of Pathophysiology and Transplantation and Fondazione Luigi Villa, Milan, Italy
Milan, Lombardia, Italy
RF

Rebekah Fretwell

Scientist
Department of Coagulation Sheffield Laboratory Medicine Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, England, United Kingdom
Adam Cuker, MD, MS (he/him/his)

Associate Professor
Department of Medicine and Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Philadelphia, Pennsylvania, United States
KS

Kristi Smock

Department of Pathology and ARUP Laboratories
University of Utah
Salt Lake City, Utah, United States
Piet Meijer, PhD

Director
ECAT Foundation
Voorschoten, Zuid-Holland, Netherlands
Nikolaus B. Binder, MD PhD

CSO
Technoclone Herstellung von Diagnostika und Arzneimitteln GmbH, Vienna, Austria
Vienna, Wien, Austria
Flora Peyvandi, MD, PhD (she/her/hers)

Director
IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
Milano, Lombardia, Italy
Long Zheng, MD, PhD

Professor
University of Kansas Medical Centre
Kansas City, Kansas, United States
Sandra Haberichter, PhD

Director, Hemostasis, Senior Investigator
Versiti Blood Research Institute
Milwaukee, Wisconsin, United States
KV

Karen Vanhooreelbeke

Professor
Laboratory for Thrombosis Research KU Leuven Campus
Kortrijk, West-Vlaanderen, Belgium
JK

Johanna A. Kremer-Hovinga

Professor
Centre of Laboratory Medicine Section Hemostasis Inselspital Bern
Bern, Bern, Switzerland

Background: The interpretation of an ADAMTS-13 activity level secures the diagnosis of thrombotic thrombocytopenic purpura (TTP) and defines the success of treatment and TTP relapse. If the ADAMTS-13 activity is low, ADAMTS-13 antibody assessment differentiates immune-mediated (iTTP) from congenital (cTTP). ADAMT-13 activity uses different assay methods (FRETS, ELISA or chemiluminescence), as does autoantibody testing (ELISA immunoassay or functional Bethesda Unit (BU) assay). Therefore, there is an unmet need for international standardisation of ADAMTS-13 testing and clinical interpretation of results for appropriate and cost-effective TTP management.

Aims: To assess international differences and clinical interpretation of ADAMTS-13 testing within the IMATAS network of 16 laboratories from the USA, European Union, United Kingdom, Switzerland, Japan, Malaysia, Argentina, and Australia.

Methods: Seven lyophilized plasma samples were sent to test normal, borderline ADAMTS-13 activity level (5-7 IU/dl), high and low titre ADAMTS-13 antibodies and strong and non-inhibitory functional antibodies to 16 laboratories for ADAMTS13-testing according to their local protocols. In addition, sites completed a questionnaire on assay methodology and the clinical interpretation of the result.

Results: All laboratories found universal consensus for TTP diagnosis except in the borderline ADAMTS-13 sample. Differentiating a low titre ADAMTS-13 antibody up to 22 IU/ml from normal is problematic. We observed a consistent linear ADAMTS-13 antibody dose response to serial dilution. The BU assay was performed in 6/16 laboratories, and the incubation time varied from 30 minutes to 2 hours. Defining a cut-off value for normal and low titre functional BU antibodies is difficult around the 1 BU/ml.

Conclusion(s): TTP can be diagnosed reliably by ADAMTS-13 activity testing, except in those with a borderline level. The reliance on serological or function ADAMTS-13 antibody measurement to differentiate between iTTP and cTTP requires further standardisation by defining assay conditions, units of measurement, and clarification of normal ranges.