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

A. Philippe1, R. CHOCRON2, G. BONNET3, N. YATIM4, W. SUTTER5, J. HADJADJ6, O. WEIZMAN7, C. L. GUERIN8, T. Mirault9, C. SAMAMA10, B. Planquette11, B. TERRIER12, V. WALDMANN13, M. FONTENAY14, O. Sanchez15, J. DIEHL15, P. GAUSSEM16, A. COHEN17, N. Gendron18, D. Smadja19

1Université de Paris, Innovative Therapies in Haemostasis, INSERM, F-75006, Paris, France, Paris, Ile-de-France, France, 24Department of Emergency, AP-HP, Georges Pompidou European Hospital, Paris, France, Paris, Ile-de-France, France, 3Paris 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, 4Department 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, 5Paris 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, 6Imagine Institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Université de Paris, Paris, France, Paris, Ile-de-France, France, 7Centre Hospitalier Régional Universitaire de Nancy, 54511 Vandœuvre-Lès-Nancy, France., Paris, Ile-de-France, France, 8Institut Curie, Paris, France, Paris, Ile-de-France, France, 9HEGP, Paris, Ile-de-France, France, 10Intensive Care Medicine and Reanimation Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France., Paris, Ile-de-France, France, 11APHP, Paris, Ile-de-France, France, 12Internal Medicine Department, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France, Paris, Ile-de-France, France, 13Université 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, 14Université de Paris, Institut Cochin, INSERM, Paris, France, Paris, Ile-de-France, France, 15Innovative Therapies in Haemostasis, INSERM, Université de Paris, Paris, France, Paris, Ile-de-France, France, 16Department of Biological Hematology, European Hospital Georges Pompidou, AP-HP, Innovative Therapies in Haemostasis, Paris University, INSERM U1140, Paris, France, Paris, Ile-de-France, France, 17Cardiology Department Saint-Antoine Hospital, Paris, France, Paris, Ile-de-France, France, 18Hôpital européen Georges Pompidou, Inserm UMRS_1140, Paris, Ile-de-France, France, 19HEGP, Inserm UMRS_1140, Paris, Ile-de-France, France

Abstract Number: PB0083

Meeting: ISTH 2022 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Clinical

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.

To cite this abstract in AMA style:

Philippe A, CHOCRON R, BONNET G, YATIM N, SUTTER W, HADJADJ J, WEIZMAN O, GUERIN CL, Mirault T, SAMAMA C, Planquette B, TERRIER B, WALDMANN V, FONTENAY M, Sanchez O, DIEHL J, GAUSSEM P, COHEN A, Gendron N, Smadja D. Platelet activation and COVID-19 mortality: insights from coagulopathy, antiplatelet therapy and inflammation [abstract]. https://abstracts.isth.org/abstract/platelet-activation-and-covid-19-mortality-insights-from-coagulopathy-antiplatelet-therapy-and-inflammation/. Accessed October 1, 2023.

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