Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation

Aurélien Philippe; Richard Chocron; Guillaume Bonnet; Nader Yatim; Willy Sutter; Jérôme Hadjadj; Orianne Weizman; Coralie L Guerin; Tristan Mirault; Charles Fauvel; Caroline Hauw-Berlemont; Charles-Marc Samama; Benjamin Terrier; Benjamin Planquette; Victor Waldmann; Michaela Fontenay; Olivier Sanchez; Jean-Luc Diehl; Pascale Gaussem; Ariel Cohen; Nicolas Gendron; David M Smadja

doi:10.1016/j.acvd.2023.01.006

Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation

Arch Cardiovasc Dis. 2023 Apr;116(4):183-191. doi: 10.1016/j.acvd.2023.01.006. Epub 2023 Feb 14.

Authors

Aurélien Philippe¹, Richard Chocron², Guillaume Bonnet³, Nader Yatim⁴, Willy Sutter⁵, Jérôme Hadjadj⁶, Orianne Weizman⁷, Coralie L Guerin⁸, Tristan Mirault⁹, Charles Fauvel¹⁰, Caroline Hauw-Berlemont¹¹, Charles-Marc Samama¹², Benjamin Terrier¹³, Benjamin Planquette¹⁴, Victor Waldmann¹⁵, Michaela Fontenay¹⁶, Olivier Sanchez¹⁴, Jean-Luc Diehl¹⁷, Pascale Gaussem¹, Ariel Cohen¹⁸, Nicolas Gendron¹, David M Smadja¹⁹

Affiliations

¹ Innovative Therapies in Haemostasis, Inserm, université Paris Cité, 75006 Paris, France; Department of Haematology and Biosurgical Research Laboratory (Carpentier Foundation), hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, Inserm UMR-S1140, 20, rue Leblanc, 75015 Paris, France.
² Paris Cardiovascular Research Centre (PARCC), Inserm UMR970, université Paris Cité, 75015 Paris, France; Emergency Department, hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, 75015 Paris, France.
³ Paris Cardiovascular Research Centre (PARCC), Paris Translational Research Centre for Organ Transplantation, Inserm UMR-S970, université Paris Cité, 75015 Paris, France; Medico-Surgical Unit for Valvulopathies and Cardiomyopathies, hôpital cardiologique Haut-Lévêque, université de Bordeaux, 33600 Pessac, France.
⁴ Department of Internal Medicine, National Reference Centre for Rare Systemic Autoimmune Diseases, hôpital Cochin, AP-HP, AP-HP.CUP, 75014 Paris, France; Translational Immunology Laboratory, Department of Immunology, institut pasteur, 75015 Paris, France.
⁵ Paris Cardiovascular Research Centre (PARCC), Paris Translational Research Centre for Organ Transplantation, Inserm UMR-S970, université Paris Cité, 75015 Paris, France; Department of Vascular Surgery, hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, 75015 Paris, France.
⁶ Department of Internal Medicine, National Referral Centre for Rare Systemic Autoimmune Diseases, AP-HP, AP-HP-CUP, université de Paris, 75013 Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, Inserm UMR 1163, université Paris Cité, 75015 Paris, France.
⁷ Centre hospitalier régional universitaire de Nancy, 54511 Vandœuvre-lès-Nancy, France.
⁸ Innovative Therapies in Haemostasis, Inserm, université Paris Cité, 75006 Paris, France; Cytometry Platform, institut Curie, 75005 Paris, France.
⁹ Paris Cardiovascular Research Centre (PARCC), Inserm UMR970, université Paris Cité, 75015 Paris, France; Vascular Medicine, HyperVASC and DMU CARTE, hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, 75015 Paris, France.
¹⁰ Department of Cardiology, Rouen University Hospital, FHU REMOD-VHF, 76000 Rouen, France.
¹¹ Intensive Care Medicine Department, hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, 75015 Paris, France.
¹² Université de Paris, Inserm, Innovative Therapies in Haemostasis, 75006 Paris, France; Department of Anaesthesia, Intensive Care and Perioperative Medicine, AP-HP, AP-HP.CUP, Centre - université de Paris - Cochin Hospital, Paris, France.
¹³ Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, AP-HP.CUP, hôpital Cochin, Paris, France.
¹⁴ Innovative Therapies in Haemostasis, Inserm, université Paris Cité, 75006 Paris, France; Respiratory Medicine Department and Biosurgical Research Laboratory (Carpentier Foundation), AP-HP, AP-HP.CUP, 75015 Paris, France.
¹⁵ Paris Cardiovascular Research Centre (PARCC), université de Paris Cité, Inserm, 75015 Paris, France; Adult Congenital Heart Disease Medico-Surgical Unit, Hôpital Européen Georges-Pompidou, AP-HP, AP-HP.CUP, 75015 Paris, France; Electrophysiology Unit, Hôpital Européen Georges-Pompidou, 75015 Paris, France.
¹⁶ Université Paris Cité, CNRS, Inserm, institut Cochin, 75014 Paris, France; Laboratory of Hematology, Assistance publique-Hôpitaux de Paris, centre-université de Paris, Cochin Hospital, AP-HP, AP-HP.CUP, 75014 Paris, France.
¹⁷ Innovative Therapies in Haemostasis, Inserm, université Paris Cité, 75006 Paris, France; Intensive Care Medicine Department, hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, 75015 Paris, France.
¹⁸ Department of Cardiology, Saint-Antoine and Tenon Hospital, AP-HP, Inserm UMRS-ICAN 1166 and Sorbonne université, 75013 Paris, France.
¹⁹ Innovative Therapies in Haemostasis, Inserm, université Paris Cité, 75006 Paris, France; Department of Haematology and Biosurgical Research Laboratory (Carpentier Foundation), hôpital européen Georges-Pompidou, AP-HP, AP-HP.CUP, Inserm UMR-S1140, 20, rue Leblanc, 75015 Paris, France. Electronic address: david.smadja@aphp.fr.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy.

Aim: To assess if platelet activation influences mortality in COVID-19.

Methods: We explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality.

Results: In cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876-54,678)pg/mL; sCD40L 1914 (interquartile range 1410-2367)pg/mL (P<0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P=0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64-12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80-1.37; P=0.73).

Conclusions: Although we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort.

Keywords: Antiplatelet drugs; Biomarkers; COVID-19; Coagulopathy; Platelets.

MeSH terms

Biomarkers
COVID-19*
Humans
Inflammation / diagnosis
Inflammation / drug therapy
Platelet Activation
Platelet Aggregation Inhibitors* / adverse effects

Substances

Platelet Aggregation Inhibitors
Biomarkers