PB1065 - Microvesicles display opposite coagulolytic balances according to their cellular origin and activation status

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

AK

Akhil Antony Konkoth, MSc

PhD
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France

Co-Author(s)

AB

Amandine Bonifay

PhD
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
CC

Corinne Chareyre

Engineer
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
EA

Evelyne Abdili

Engineer
Biogenopole, APHM
Marseille, Provence-Alpes-Cote d'Azur, France
LP

Lea Plantureux

Postdoc
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
SR

Stéphane Robert

Senior Engineer
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
CF

Corentin FRANCO

Project manager, Research & Dedevelopment
Biocytex
Marseille, Provence-Alpes-Cote d'Azur, France
TB

Tarik BOURICHE

Head of Hemostasis and Hematology Department, Research & Research & Dedevelopment
Biocytex
Marseille, Provence-Alpes-Cote d'Azur, France
SC

Sylvie Cointe

Assistant Professor
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
PP

Philippe Poncelet

Scentific advisor at Stago
Stago
Marseille, Provence-Alpes-Cote d'Azur, France

Presenting Author(s)

Françoise Dignat-George

Professor, Director at C2VN
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France

Co-Author(s)

Rory R. Koenen, PhD (he/him/his)

Professor of Vascular Inflammation and Thrombosis
Maastricht University
Maastricht, Limburg, Netherlands
RL

Romaric Lacroix

Professor
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France

Background: Microvesicles (MVs) display not only procoagulant but also profibrinolytic properties. Therefore, their effects on hemostasis may result from an equilibrium between these two activities called “coagulolytic balance”. However, the variations of this MV coagulolytic balance have not been investigated in different subpopulations of MVs based on their cellular origin and activation status of the parental cells.

Aims: Therefore, we investigated the coagulolytic balance profile and functional consequences of the main circulating subsets of MVs.

Methods: MVs from monocyte, neutrophil, endothelial cell, and platelet origin were generated either in vitro from both unstimulated and stimulated purified human primary cells or directly isolated from the human plasma of healthy donors or septic patients by specific immunomagnetic separation. Their procoagulant and profibrinolytic activities were assessed by performing a panel of functional assays including Factor Xa, Thrombin and Plasmin generation assays, fibrin density assay, and fibrinography.

Results: Purified MVs from monocyte and endothelial cells displayed a higher procoagulant profile than MVs from neutrophils and platelets as evidenced by higher FXa generation (22±4.6 and 18.3±3.8 OD/min vs 0.4±0.2 and 0.3±0.2 OD/min, p< 0.001, respectively) and thrombin generation (107±23 and 55±24 Peak nM vs 8±11 and 10±14 mOD/min, respectively) that was dependent on tissue factor (TF). Clots prepared by these procoagulant MVs were denser due to faster fibrin polymerization and displayed more clot stability and resistance to fibrinolysis. Similarly, monocyte and endothelial MVs isolated directly from plasma from patients with sepsis also showed higher FXa generation. In contrast, only MVs purified from neutrophils displayed a profibrinolytic profile exhibiting a high plasmin generation capacity both in vitro and ex vivo.

Conclusion(s): We showed the different circulating MV subsets display opposite coagulolytic balances according to their cellular origin and activation status which may contribute to their heterogenous role in thrombosis and hemostasis.