PB0310 - Exploring the behavior of ADAMTS13/VWF parameters and their roles in the PathologicalMechanisms involved in Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP).

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

SC

Santiago Castera, Sr.

Biochemist, Ms.
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina
AM

Alberto Maria Fabiana

PhD
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina
CD

Celia Dos Santos

PhD
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina
YT

Yésica Trinidad

PhD Student.
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina
AW

Adriana I. Woods, PhD

Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
Ciudad Autonoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
OG

Osvaldo Jose Guerrero

MD
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Presenting Author(s)

Analia Sánchez-Luceros, MD, PHD

MD, PhD
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina

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

Aims: To explore the behavior of ADAMTS13/VWF parameters in a cohort of consecutive
patients with acute iTTP.

Methods: We analyzed 57 acute iTTP patients (2021-2023) for ADAMTS13:Antigen
(ADAMTS13:Ag), ADAMTS13:Activity, and anti-ADAMTS13 IgG (ELISA, Technoclone).
Additionally, VWF:Ag and VWF collagen-binding (VWF:CB3) were measured through an in-
house ELISA. Patients with abnormal ADAMTS13:Ag levels were further evaluated to
determine their correlation with anti-ADAMTS13 IgG.

Results: Table 1 outlines the clinical and laboratory features (women 77%). Neurological (75%),
gastrointestinal (20%), and renal manifestations (7%) were observed. All ADAMTS13:activities
were <10IU/dL; anti-ADAMTS13 IgG median was 61 U/mL (range: 2-180U/mL). ADAMTS13:Ag
was substantially reduced (median: 7IU/dL, range: 1-77 ), with 86% of samples registering
below 20IU/dL and 95% below the normal range [Figure 1A]; with negative correlation (-0.43,
p=0.002) between ADAMTS13:Ag vs. anti-ADAMTS13 IgG in patients with abnormal
ADAMTS13:Ag ( <40IU/dL) [Figure 1B]. The VWF:CB3/VWF:Ag ratios exhibited significant
heterogeneity, with a median of 0.6 (range:0.2-1.2), and 61% of patients below 0.7.

Conclusion(s): these results suggest that the predominant pathological mechanism in the
majority of patients is mediated by increased enzyme clearance, aligning with the
concentration of anti-ADAMTS13 IgG. In contrast to our previous findings, where the 100% of
patients had presented abnormal ADAMTS13:Ag (ISTH 2023), this expanded cohort showed in
the 5% of patients that the ADAMTS13:Ag clearance was not significant. Furthermore, most of
patients displayed VWF:CB3/VWF:Ag ratios <0.7. This apparent decrease in the ratios could be
explained by the sequestration of the VWF-HMWM within the microthrombi (Béranger, 2019).