PB0330 - Relevance of ADAMTS13 antigenic levels in the characterization of pathological mechanisms associated with immune-mediated thrombotic thrombocytopenic purpura (iTTP).

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

SC

Santiago Castera, Sr.

Biochemist. Clinical laboratory assistant
Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Co-Author(s)

CD

Célia Dos Santos

PhD
Laboratorio de Hemostasia y Trombosis IMEX-CONICET-ANM y Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
Ciudad Autónoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
JT

Jésica Trinidad

PhD intern
Laboratorio de Hemostasia y Trombosis IMEX-CONICET-ANM
Cleypole, Buenos Aires, Argentina

Presenting Author(s)

Adriana I. Woods

Biochemist, PhD
Laboratorio de Hemostasia y Trombosis, IMEX-CONICET-ANM
CABA, Buenos Aires, Argentina

Co-Author(s)

FA

Fabiana F. Alberto

PhD
Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
Ciudad autonoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
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

Background: Immune-mediated thrombotic thrombocytopenic purpura is a rare and life-threatening autoimmune disease associated to severe ADAMTS13 functional deficiency mediated by anti-ADAMTS13 antibodies. Laboratory diagnosis is based on the determination of ADAMTS13 enzyme activity < 10 IU/dL and the concomitant presence of anti-ADAMTS13, predominantly the IgG isotype. Determination of ADAMTS13 antigen is usually not performed but may help identify whether enzyme deficiency is due to functional abnormality and/or increased clearance.

Aims: To determine ADAMTS13 antigen levels in a group of patients with acute iTTP.

Methods: Citrated plasma samples from a sequential cohort of 35 patients with acute iTTP, referred to our center between 2020 and 2021, were tested for ADAMTS13 Activity, anti-ADAMTS13 IgG, ADAMTS13 antigen by commercial ELISA methods (Technoclone) and VWF:Ag by an in house ELISA. All samples were processed before starting treatment (plasma exchange and/or rituximab).

Results: The clinical and laboratory characteristics are summarized in Table 1. Eighty percent of patients were female. Neurological symptoms were predominantly observed (70%), followed by gastrointestinal (21%) and renal manifestations (9%). All patients presented ADAMTS13 activity < 5 IU/dL and anti-ADAMTS13 IgG >14 U/mL. Interestingly, ADAMTS13 antigen was highly reduced (median 7 IU/dL, range 2-32) with 94% of samples under 20 IU/dL and 100% below normal range [Figure 1A], suggesting autoantibody-mediated ADAMTS13 clearance as a major pathogenic mechanism. This was emphasized by a negative correlation between ADAMTS13 antigen levels and anti-ADAMTS13 IgG titers (-0.57, p= 0.0003) [Figure 1B].

Conclusion(s): In our cohort of iTTP patients, ADAMTS13 antigen levels showed that ADAMTS13 antigen depletion rather than enzyme inhibition is a dominant pathogenic mechanism, in accordance with previous report (Thomas MR, 2015). Routine assessment of ADAMTS13 antigen could be useful to interpret the response to therapeutics in a more rational way.