PB0848 - Differences between collagen-6 binding and collagen-1 binding in type-2 VWD (preliminary study)

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Adriana I. Woods

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

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
AB

Alicia N. Blanco

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

Maria Marta M. Casinelli

Technician
Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina
MA

Maria F. Alberto

Biochemist, PhD
Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
CABA, 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: Reduced VWF-collagen-binding was associated with reduced high and intermediate molecular weight von Willebrand factor multimers (HMWM, IMWM).
Collagen-1 (C1) showed higher affinity for VWF-A3 domain (A3D); collagen-6 (C6) has higher affinity for VWF-A1domain (A1D).
We described before that C1-binding/VWF:Ag (C1B/Ag) showed different patterns according to the disease-causing variants (DCVs) location: in VWD2A with DCVs in A2D, C1B/Ag was more discordant. In VWD2M with DCVs in A1D, C1B/Ag was normal; with DCVs in A2D, C1B/Ag was discordant. The DCVs responsible for VWD2B modify the A1D conferring heightened affinity for platelet-GP1b, and VWF;RCo/VWF:Ag (RCo/Ag) is frequently normal.

Aims: To evaluate differences between C6B/Ag and C1B/Ag in type-2 VWD patients phenotypic/genotypically diagnosed.

Methods: Patients: 20 VWD2A, 42 VWD2B, 65 VWD2M.
Laboratory: C1B and C6B (ELISA).
In VWD2M, CBs/Ag were analyzed according to the DCVs location, whereas in VWD2B, according to the DCVs and the multimers.

Results: • VWD2A showed both discordant ( < 0.7) CBs/Ag, but higher C1B/Ag than C6B/Ag (p=0.014), irrespective of the DCV location (Table 1).
• VWD2M: -with DCVs in A1D: both normal CBs/Ag.
-with DCVs in A2D: both discordant CBs/Ag.
• VWD2B:CBs/Ag showed differences according to the DCV and multimers (Table 2):
-with normal HMWM: p.P1266L, p.M1304V, both normal CBs/Ag.
p.R1306W: both discordant CB/Ag.
p.V1316M: normal C6B/Ag and discordant C1B/Ag.
-with low HMWM: p.Y1258C,p.M1304V and p.P1337L: normal C6B/Ag and discordant C1B/Ag;
p.R1306W, p.R1308C, p.S1310F and p.V1316M: both discordant CBs/Ag.

Conclusion(s): In VWD2A, C6B/Ag was more sensitive than C1B/Ag mainly in cases with DCVs in A1D.
In VWD2M, DCVs in A1D do not affect both CBs/Ag. DCVs in A2D affect both CBs/Ag.
In VWD2B, p.Y1258C, p.M1304V, and p.P1337L showed normal C6B/Ag, consistent with A1D alterations. C6B/Ag might be considered a marker of hyperresponsiveness for specific DCVs. Discordant C1B/Ag was the only finding in most patients. Both CBs/Ag were useful for VWD2B diagnosis.