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Updated: Nov 19, 2025
Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Antibody-induced procoagulant platelets in severe COVID-19 infection
Karina Althaus1,2, Irene Marini1, Jan Zlamal1
1Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen.
Insights
COVID-19 patients in intensive care units show increased platelet activation, leading to higher risks of blood clots. This platelet dysfunction, linked to antibodies, contributes to thrombosis in severe COVID-19 cases.
Area of Science:
- Hematology
- Immunology
- Critical Care Medicine
Background:
- COVID-19 is associated with a high risk of thrombosis.
- The exact mechanisms driving COVID-19-associated coagulopathy are not fully understood.
- Platelet activation and dysfunction are implicated in thrombotic events.
Purpose of the Study:
- To investigate the role of procoagulant platelets in COVID-19 pathophysiology.
- To examine platelet mitochondrial inner transmembrane potential (ΔΨm) depolarization, cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization in COVID-19 patients.
- To determine the association between platelet markers, disease severity, and thrombotic events.
Main Methods:
- Compared platelet markers (ΔΨm, Ca2+, PS externalization) in intensive care unit (ICU) COVID-19 patients, non-ICU COVID-19 patients, septic ICU controls, and healthy controls.
- Assessed the effect of COVID-19 patient sera and immunoglobulin G (IgG) fractions on platelet apoptosis.
- Correlated platelet activation markers with Sequential Organ Failure Assessment (SOFA) scores, D-dimer levels, and thrombosis incidence.
Main Results:
- Platelets from ICU COVID-19 patients exhibited significantly higher ΔΨm depolarization, cytosolic Ca2+, and PS externalization compared to healthy and non-ICU COVID-19 patients.
- COVID-19 patient sera and IgG fractions induced platelet apoptosis, dependent on Fcγ receptor IIA.
- Enhanced PS externalization correlated with higher SOFA scores and D-dimer levels, and was significantly higher in patients with thrombosis.
Conclusions:
- COVID-19 is characterized by procoagulant platelets, indicated by increased mitochondrial depolarization, cytosolic calcium, and phosphatidylserine externalization.
- Antibody-mediated platelet activation contributes to thrombosis and thromboembolic risk in severe COVID-19.
- Targeting antibody-mediated platelet dysfunction may offer therapeutic strategies for COVID-19-associated coagulopathy.
Abstract:
The pathophysiology of COVID-19-associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization. Platelets from COVID-19 patients in the intensive care unit (ICU; n = 21) showed higher ΔΨm depolarization, cytosolic Ca2+, and PS externalization compared with healthy controls (n = 18) and non-ICU COVID-19 patients (n = 4). Moreover, significant higher cytosolic Ca2+ and PS were observed compared with a septic ICU control group (ICU control; n = 5). In the ICU control group, cytosolic Ca2+ and PS externalization were comparable with healthy controls, with an increase in ΔΨm depolarization. Sera from COVID-19 patients in the ICU induced a significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+, and PS externalization) compared with healthy volunteers and septic ICU controls. Interestingly, immunoglobulin G fractions from COVID-19 patients induced an Fcγ receptor IIA-dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+, and PS externalization). Enhanced PS externalization in platelets from COVID-19 patients in the ICU was associated with increased sequential organ failure assessment score (r = 0.5635) and D-dimer (r = 0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared with those without. The strong correlations between markers for apoptosic and procoagulant platelets and D-dimer levels, as well as the incidence of thrombosis, may indicate that antibody-mediated procoagulant platelets potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.
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