tetano
Editor, Senior Moderator
Arch Cardiovasc Dis
. 2023 Feb 14;S1875-2136(23)00050-5.
doi: 10.1016/j.acvd.2023.01.006. Online ahead of print.
Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation
Aurélien Philippe[SUP] 1 [/SUP], Richard Chocron[SUP] 2 [/SUP], Guillaume Bonnet[SUP] 3 [/SUP], Nader Yatim[SUP] 4 [/SUP], Willy Sutter[SUP] 5 [/SUP], Jérôme Hadjadj[SUP] 6 [/SUP], Orianne Weizman[SUP] 7 [/SUP], Coralie L Guerin[SUP] 8 [/SUP], Tristan Mirault[SUP] 9 [/SUP], Charles Fauvel[SUP] 10 [/SUP], Caroline Hauw-Berlemont[SUP] 11 [/SUP], Charles-Marc Samama[SUP] 12 [/SUP], Benjamin Terrier[SUP] 13 [/SUP], Benjamin Planquette[SUP] 14 [/SUP], Victor Waldmann[SUP] 15 [/SUP], Michaela Fontenay[SUP] 16 [/SUP], Olivier Sanchez[SUP] 14 [/SUP], Jean-Luc Diehl[SUP] 17 [/SUP], Pascale Gaussem[SUP] 1 [/SUP], Ariel Cohen[SUP] 18 [/SUP], Nicolas Gendron[SUP] 1 [/SUP], David M Smadja[SUP] 19 [/SUP]
Affiliations
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.
. 2023 Feb 14;S1875-2136(23)00050-5.
doi: 10.1016/j.acvd.2023.01.006. Online ahead of print.
Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation
Aurélien Philippe[SUP] 1 [/SUP], Richard Chocron[SUP] 2 [/SUP], Guillaume Bonnet[SUP] 3 [/SUP], Nader Yatim[SUP] 4 [/SUP], Willy Sutter[SUP] 5 [/SUP], Jérôme Hadjadj[SUP] 6 [/SUP], Orianne Weizman[SUP] 7 [/SUP], Coralie L Guerin[SUP] 8 [/SUP], Tristan Mirault[SUP] 9 [/SUP], Charles Fauvel[SUP] 10 [/SUP], Caroline Hauw-Berlemont[SUP] 11 [/SUP], Charles-Marc Samama[SUP] 12 [/SUP], Benjamin Terrier[SUP] 13 [/SUP], Benjamin Planquette[SUP] 14 [/SUP], Victor Waldmann[SUP] 15 [/SUP], Michaela Fontenay[SUP] 16 [/SUP], Olivier Sanchez[SUP] 14 [/SUP], Jean-Luc Diehl[SUP] 17 [/SUP], Pascale Gaussem[SUP] 1 [/SUP], Ariel Cohen[SUP] 18 [/SUP], Nicolas Gendron[SUP] 1 [/SUP], David M Smadja[SUP] 19 [/SUP]
Affiliations
- PMID: 36858909
- DOI: 10.1016/j.acvd.2023.01.006
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.