Résumé

Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by the susceptibility of blood cells to attack by the complement system, inducing extracellular vesicle (EV) production. Thromboembolism is the leading cause of death in this condition. Eculizumab, a humanized monoclonal antibody which inhibits the C5 protein of the complement, reduces the thrombotic risk in PNH. Materials and method We conducted a pilot, prospective, open-label, longitudinal clinical study with six PNH patients treated with eculizumab. The aim was to measure, by flow cytometry, the EVs’ production in the patients’ platelet-free plasma (PFP) before and during the treatment. We also assessed the procoagulant activity in PFP using STA®-Procoag-PPL and thrombin generation assays (TGA). A high-sensitive version of TGA was also used to study the procoagulant profile induced by the EVs using EVs pelleted from PFP. Results We observed a decrease in platelet EV count with eculizumab treatment (p < 0.05). STA®-Procoag-PPL assay showed a decrease of the procoagulant profile induced by procoagulant phospholipids (PL) during treatment. These results were not confirmed by TGA on PFP, due to a lack of sensitivity. Thus, we used a high-sensitive version of TGA that enabled us to observe variation in the procoagulant profile induced by the EVs with eculizumab (p < 0.05). Conclusions Eculizumab has an impact on the extent of EV production and on the procoagulant profile induced by the procoagulant PL and the EVs. One factor in the antithrombotic action of eculizumab is its ability to decrease EV production and the procoagulant profile induced by PL and EVs.

langue originaleAnglais
Pages (de - à)142-148
Nombre de pages7
journalThrombosis Research
Volume156
Date de mise en ligne précoce2017
Les DOIs
étatPublié - 1 août 2017

Empreinte digitale

Paroxysmal Hemoglobinuria
Longitudinal Studies
Blood Platelets
Thrombin
Phospholipids
Complement C5
Antibodies, Monoclonal, Humanized
Thromboembolism
Disease Susceptibility
Extracellular Vesicles
Clinical Studies
eculizumab
Cause of Death
Blood Cells
Flow Cytometry
Complement System Proteins
Therapeutics

Citer ceci

@article{79fcc5c5d28e4affa26e2ecd380cc62f,
title = "Eculizumab decreases the procoagulant activity of extracellular vesicles in paroxysmal nocturnal hemoglobinuria: A pilot prospective longitudinal clinical study.",
abstract = "Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by the susceptibility of blood cells to attack by the complement system, inducing extracellular vesicle (EV) production. Thromboembolism is the leading cause of death in this condition. Eculizumab, a humanized monoclonal antibody which inhibits the C5 protein of the complement, reduces the thrombotic risk in PNH. Materials and method We conducted a pilot, prospective, open-label, longitudinal clinical study with six PNH patients treated with eculizumab. The aim was to measure, by flow cytometry, the EVs’ production in the patients’ platelet-free plasma (PFP) before and during the treatment. We also assessed the procoagulant activity in PFP using STA{\circledR}-Procoag-PPL and thrombin generation assays (TGA). A high-sensitive version of TGA was also used to study the procoagulant profile induced by the EVs using EVs pelleted from PFP. Results We observed a decrease in platelet EV count with eculizumab treatment (p < 0.05). STA{\circledR}-Procoag-PPL assay showed a decrease of the procoagulant profile induced by procoagulant phospholipids (PL) during treatment. These results were not confirmed by TGA on PFP, due to a lack of sensitivity. Thus, we used a high-sensitive version of TGA that enabled us to observe variation in the procoagulant profile induced by the EVs with eculizumab (p < 0.05). Conclusions Eculizumab has an impact on the extent of EV production and on the procoagulant profile induced by the procoagulant PL and the EVs. One factor in the antithrombotic action of eculizumab is its ability to decrease EV production and the procoagulant profile induced by PL and EVs.",
keywords = "Eculizumab, Extracellular vesicles, Paroxysmal nocturnal hemoglobinuria, Thrombosis",
author = "Adeline Wannez and B{\'e}rang{\`e}re Devalet and C{\'e}line Bouvy and Julie Laloy and Beno{\^i}t Bihin and Bernard Chatelain and Christian Chatelain and Jean-Michel Dogne and Fran{\cc}ois Mullier",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.thromres.2017.06.013",
language = "English",
volume = "156",
pages = "142--148",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Elsevier",

}

TY - JOUR

T1 - Eculizumab decreases the procoagulant activity of extracellular vesicles in paroxysmal nocturnal hemoglobinuria: A pilot prospective longitudinal clinical study.

AU - Wannez, Adeline

AU - Devalet, Bérangère

AU - Bouvy, Céline

AU - Laloy, Julie

AU - Bihin, Benoît

AU - Chatelain, Bernard

AU - Chatelain, Christian

AU - Dogne, Jean-Michel

AU - Mullier, François

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by the susceptibility of blood cells to attack by the complement system, inducing extracellular vesicle (EV) production. Thromboembolism is the leading cause of death in this condition. Eculizumab, a humanized monoclonal antibody which inhibits the C5 protein of the complement, reduces the thrombotic risk in PNH. Materials and method We conducted a pilot, prospective, open-label, longitudinal clinical study with six PNH patients treated with eculizumab. The aim was to measure, by flow cytometry, the EVs’ production in the patients’ platelet-free plasma (PFP) before and during the treatment. We also assessed the procoagulant activity in PFP using STA®-Procoag-PPL and thrombin generation assays (TGA). A high-sensitive version of TGA was also used to study the procoagulant profile induced by the EVs using EVs pelleted from PFP. Results We observed a decrease in platelet EV count with eculizumab treatment (p < 0.05). STA®-Procoag-PPL assay showed a decrease of the procoagulant profile induced by procoagulant phospholipids (PL) during treatment. These results were not confirmed by TGA on PFP, due to a lack of sensitivity. Thus, we used a high-sensitive version of TGA that enabled us to observe variation in the procoagulant profile induced by the EVs with eculizumab (p < 0.05). Conclusions Eculizumab has an impact on the extent of EV production and on the procoagulant profile induced by the procoagulant PL and the EVs. One factor in the antithrombotic action of eculizumab is its ability to decrease EV production and the procoagulant profile induced by PL and EVs.

AB - Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by the susceptibility of blood cells to attack by the complement system, inducing extracellular vesicle (EV) production. Thromboembolism is the leading cause of death in this condition. Eculizumab, a humanized monoclonal antibody which inhibits the C5 protein of the complement, reduces the thrombotic risk in PNH. Materials and method We conducted a pilot, prospective, open-label, longitudinal clinical study with six PNH patients treated with eculizumab. The aim was to measure, by flow cytometry, the EVs’ production in the patients’ platelet-free plasma (PFP) before and during the treatment. We also assessed the procoagulant activity in PFP using STA®-Procoag-PPL and thrombin generation assays (TGA). A high-sensitive version of TGA was also used to study the procoagulant profile induced by the EVs using EVs pelleted from PFP. Results We observed a decrease in platelet EV count with eculizumab treatment (p < 0.05). STA®-Procoag-PPL assay showed a decrease of the procoagulant profile induced by procoagulant phospholipids (PL) during treatment. These results were not confirmed by TGA on PFP, due to a lack of sensitivity. Thus, we used a high-sensitive version of TGA that enabled us to observe variation in the procoagulant profile induced by the EVs with eculizumab (p < 0.05). Conclusions Eculizumab has an impact on the extent of EV production and on the procoagulant profile induced by the procoagulant PL and the EVs. One factor in the antithrombotic action of eculizumab is its ability to decrease EV production and the procoagulant profile induced by PL and EVs.

KW - Eculizumab

KW - Extracellular vesicles

KW - Paroxysmal nocturnal hemoglobinuria

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=85020848861&partnerID=8YFLogxK

U2 - 10.1016/j.thromres.2017.06.013

DO - 10.1016/j.thromres.2017.06.013

M3 - Article

VL - 156

SP - 142

EP - 148

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

ER -