Related Experiment Video
Updated: Aug 8, 2025
Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and
Aurélien Philippe1, Richard Chocron2, Guillaume Bonnet3
1Innovative 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.
Insights
Platelet activation biomarkers were associated with COVID-19 mortality, but coagulopathy markers like D-dimer were more central. Pre-hospitalization antiplatelet drugs did not significantly impact mortality in this COVID-19 study.
Area of Science:
- Immunothrombosis
- COVID-19 Pathophysiology
- Platelet Biology
Background:
- COVID-19 is linked to inflammatory cytokine release and prothrombotic coagulopathy.
- Platelets may play a role in microthrombosis and are a potential therapeutic target in COVID-19.
Purpose of the Study:
- To investigate the association between platelet activation and in-hospital mortality in COVID-19 patients.
- To determine if platelet activation biomarkers are independent predictors of mortality.
Main Methods:
- Two cohorts of COVID-19 patients were analyzed for in-hospital mortality.
- Plasma concentrations of soluble platelet activation biomarkers (sCD40L, sP-sel) were measured.
- Cox models were used to assess the association of biomarkers and antiplatelet agents with mortality.
Main Results:
- Elevated sP-sel and sCD40L concentrations were observed in critical COVID-19 patients.
- sP-sel concentration showed an initial association with mortality, but this was not independent of coagulopathy markers.
- D-dimer concentration was significantly associated with mortality.
- Prehospitalization antiplatelet agent use did not significantly impact in-hospital mortality.
Conclusions:
- While platelet activation markers correlate with mortality, coagulopathy appears more critical in driving COVID-19 progression.
- The lack of benefit from antiplatelet drugs suggests coagulopathy, not platelet activation alone, is the primary driver of mortality.
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.
Related Concept Videos
01:22Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:18Structure and Function of Platelets
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
01:38Inflammation
01:05Introduction to Hemostasis
The three phases of hemostasis involve many clotting factors present in plasma and several substances released by platelets and injured tissue cells. It is a fast, localized,...