PB0083 - Platelet activation and COVID-19 mortality: insights from coagulopathy, antiplatelet therapy and inflammation

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Aurelien Philippe

PhD student
UniVersité Paris Cité et Inserm 1140
Paris, Ile-de-France, France

Co-Author(s)

RC

Richard Chocron

Assistant Professor
AP-HP
Paris, Ile-de-France, France
GB

Guillaume BONNET

Interventional cardiologist. MD, PhD
Paris Cardiovascular Research Center (PARCC), Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Université de Paris, 75015 Paris, France.
Paris, Ile-de-France, France
NY

Nader YATIM

Resident in Internal Medecine and Clinical Immunology
Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP Hôpital Cochin, Paris, France; Translational Immunology Lab, Department of Immunology, Institut Pasteur, Paris, France.
Paris, Ile-de-France, France
WS

Willy SUTTER

Vascular Surgeon MD
Paris Cardiovascular Research Center (PARCC), Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Université de Paris, 75015 Paris, France
Paris, Ile-de-France, France
JH

Jérôme HADJADJ

Internal medicine physician, MD, PHD
Imagine Institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Université de Paris, Paris, France
Paris, Ile-de-France, France
OW

Orianne WEIZMAN

Cardiologist, MD
Centre Hospitalier Régional Universitaire de Nancy, 54511 Vandœuvre-Lès-Nancy, France.
Paris, Ile-de-France, France
CL

Coralie L. GUERIN, PhD

Biologist PhD
Institut Curie, Paris, France
Paris, Ile-de-France, France
TM

Tristan Mirault

Vascular medicine
HEGP
Paris, Ile-de-France, France
CS

Charles-Marc SAMAMA

Internal medicine physician, MD, PHD
Intensive Care Medicine and Reanimation Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.
Paris, Ile-de-France, France
BP

Benjamin Planquette

Physician MD
APHP
Paris, Ile-de-France, France
BT

Benjamin TERRIER

Internal medicine physician, MD, PHD
Internal Medicine Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France
Paris, Ile-de-France, France
VW

Victor WALDMANN

Cardiologist, MD
Université de Paris, PARCC, INSERM, Paris, France; Adult Congenital Heart Disease Medico-Surgical Unit, European Georges Pompidou Hospital, Paris, France; Electrophysiology Unit, European Georges Pompidou Hospital, Paris, France
Paris, Ile-de-France, France
MF

Michaela Fontenay

Professor
Service Hematologie Biologique et UF Hemostase Clinique, Hopital Cochin AP-HP.Centre - Universite Paris Cite
Paris, Ile-de-France, France
OS

Olivier Sanchez

MD, PhD
Georges Pompidou European Hospital, Paris, France
Paris, Ile-de-France, France
JD

Jean-Luc DIEHL

Professor
AP-HP
Paris, Ile-de-France, France
PG

Pascale Gaussem

Professor
Université Paris Cité, INSERM U1140, Innovative Therapies in Haemostasis, France
Paris, Ile-de-France, France
AC

Ariel COHEN

Cardiologist. MD, PhD
Cardiology Department Saint-Antoine Hospital, Paris, France
Paris, Ile-de-France, France
Ng

Nicolas gendron, PharmD, PhD

Clinical fellow
AP-HP
Paris, Ile-de-France, France
DS

David M. Smadja

Professor
Université Paris Cité, INSERM U1140, Innovative Therapies in Haemostasis, France
Paris, Ile-de-France, France

Background: Severe coronavirus disease 2019 (COVID-19) is associated with inflammatory cytokine burst and coagulopathy. Platelets may contribute to microthrombosis development and be a target in COVID-19 therapy.

Aims: To determine the significance of platelet activation and antiplatelet agents (APAs) treatment in COVID-19 pathophysiology and mortality in two cohorts of patients with COVID-19.

Methods: We explored two cohorts of COVID-19 patients: cohort A (NCT04624997) included 208 ambulatory and hospitalized patients of different clinical severity with evaluation of soluble CD40 ligand (sCD40L) and P-selectin (sP-sel) plasma levels of within the first 48 hours following admission. Cohort B included 2878 patients initially admitted in medical ward with collection of clinical characteristics and outcomes (NCT04344327). In both cohorts, the primary outcome was in-hospital mortality.

Results: In cohort A, circulating median levels of sCD40L and sP-sel were significantly increased solely in critical patients with COVID-19 (sP-sel: 40059 pg/mL, IQR 26876−54678; sCD40L: 1914 pg/mL IQR 1410−2367; p< 0.001 for both), signaling platelet hyper-activation. However, pre-hospitalization APAs did not significantly modified sCD40L and sP-sel levels. Admission sP-sel levels were predictive in-hospital mortality (Kaplan–Meier log-rank p=0.004), even after adjustment on CRP, while adjustment on D-dimer abolished this relationship, suggesting that platelet activation is highly interrelated with coagulopathy. We confirmed this finding in a Cox model adjusted for age, sex, CRP and D-dimer levels (Odds ratio 1.78, 95% CI 0.63–4.50). We confirmed in cohort B (2878 patients) that, among patients receiving APA before hospitalization, there was no significant difference in the proportion of death in a Cox model (Hazard ratio 1.0, IQR0.77–1.30) adjusted for demographic comorbidities.

Conclusion(s): Our findings highlight the critical role of coagulopathy, in contrast to platelet activation, in discriminating COVID‐19 severity and increased risk of in‐hospital mortality. We also confirm that APAs before hospitalization do not influence neither mortality nor platelet activation.