PB0086 - Prospective Assessment of thrombomodulin resistance in Oncological Patients and healthy subjects Following Vaccination against Sars-Cov-2 with the mRNA Vaccine. The Roadmap-COVID-19-Vaccin Study

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Patrick Van Dreden, PhD

PhD clinical research manager
Clinical Research Department, Diagnostica Stago
Gennevilliers, Ile-de-France, France

Co-Author(s)

JG

Joseph Gligorov

Professor of Oncology
Université de la Sorbonne et Praticien Hospitalier au Département d'oncologie médicale de l'hôpital Tenon, Paris
Paris, Ile-de-France, France
ET

Evangelos Terpos

Professor of Haematology
Department of Clinical Therapeutics in the University of Athens, School of Medicine, Athens,
Athens, Attiki, Greece
MJ

Methieu Jamelot

anesthetist
Medical Oncology Department, Hôpital Tenon, Assistance Publique Hôpitaux de Paris (APHP)
Paris, Ile-de-France, France
MG

Matthieu Grussé

Ingeneer, Clinical Research Department
Diagnostica Stago
Gennevilliers, Ile-de-France, France
IE

Ismail Elalamy

Director of Hematology Department of Thrombosis Center, Tenon University Hospital
Medicine Sorbonne University
Paris, Ile-de-France, France
JF

Jawed Fareed

Professor of Pathology and Laboratory Medicine
Loyola University Medical center
Maywood, Illinois, United States
AR

Aurélie Rousseau

PhD, Clinical Research Department
Diagnostica Stago
Gennevilliers, Ile-de-France, France
MD

Meletios A Dimopoulos

Professor and Chairman of the Department of Clinical Therapeutics
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens
Athens, Attiki, Greece
Grigorios Gerotziafas

Pr
Research Group "Cancer - Hemostasis - Angiogenesis" Thrombosis Center
Paris, Ile-de-France, France

Background: Cancer has been associated with hypercoagulability, and frequent thrombotic complications. In protein C pathway one of the major inhibitor of coagulation, thrombomodulin plays a central role. Thrombomodulin can be reduced following the release of angiopoietin-2 by the endothelium during the inflammatory process.

Aims: Explore the impact of thrombomodulin on blood hypercoagulability and to investigate if there are modified by the severity of the disease in active vaccinated cancer.

Methods: Patients with active cancer (n= 80) vaccinated with mRNA anti-SARS-CoV-2 vaccine (Pfizer), non-vaccinated healthy subjects (control group; n=30) and vaccinated healthy individuals (n=30) were studied.Patients were stratified according to the presence of cancer associated thrombosis (CAT). Thrombin generation (TG) in presence and absence of TM was assessed. Biomarkers of hypercoagulability and endothelial cell activation were measured. The upper and lower normal limits (UNL and LNL) for each biomarker were defined by the mean±2SD for the control group.

Results: Cancer patients showed a profile of TG without TM noticeably comparable to that of healthy subjects. The measurement of ETP or MRI with/without TM showed a significant difference between patients versus healthy controls; 62 % of patients had ETP inhibition < 43% and 53% had MRI inhibition < 82%. TG test with TM revealed a significant resistance to TM in the group of patients with metastasis and CAT (35% for ETP and 29 % for MRI) as compared to those with localized disease or without CAT. In the same way, the indexes FVIII/DDimer and FvW/DDimer showed a strong difference between patients versus healthy controls, with more than 15% of Low FVIII/DDi and FVW/DDi index levels in localized cancer patients with CAT and with metastasis in more 35% of patients (Table 1).

Conclusion(s): Analysis of thrombomodulin resistance can be a powerful tool for risk stratification of cancer patients and can be prospectively incorporated into a RAM for CAT.