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Updated: Oct 11, 2025
Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
Binding of phosphatidylserine-positive microparticles by PBMCs classifies disease severity in COVID-19 patients
Lisa Rausch1, Konstantin Lutz1, Martina Schifferer2,3
1Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany.
Abstract:
Infection with SARS-CoV-2 is associated with thromboinflammation, involving thrombotic and inflammatory responses, in many COVID-19 patients. In addition, immune dysfunction occurs in patients characterised by T cell exhaustion and severe lymphopenia. We investigated the distribution of phosphatidylserine (PS), a marker of dying cells, activated platelets and platelet-derived microparticles (PMP), during the clinical course of COVID-19. We found an unexpectedly high amount of blood cells loaded with PS+ PMPs for weeks after the initial COVID-19 diagnosis. Elevated frequencies of PS+ PMP+ PBMCs correlated strongly with increasing disease severity. As a marker, PS outperformed established laboratory markers for inflammation, leucocyte composition and coagulation, currently used for COVID-19 clinical scoring. PS+ PMPs preferentially bound to CD8+ T cells with gene expression signatures of proliferating effector rather than memory T cells. As PS+ PMPs carried programmed death-ligand 1 (PD-L1), they may affect T cell expansion or function. Our data provide a novel marker for disease severity and show that PS, which can trigger the blood coagulation cascade, the complement system, and inflammation, resides on activated immune cells. Therefore, PS may serve as a beacon to attract thromboinflammatory processes towards lymphocytes and cause immune dysfunction in COVID-19.
Insights
Phosphatidylserine (PS) on platelet-derived microparticles (PMPs) marks severe COVID-19 by binding to T cells, potentially causing immune dysfunction and attracting thromboinflammation.
Area of Science:
- Immunology
- Hematology
- Pathophysiology
Background:
- COVID-19 is linked to thromboinflammation and immune dysfunction, including T cell exhaustion and lymphopenia.
- Activated platelets and platelet-derived microparticles (PMPs) play a role in these processes.
Purpose of the Study:
- To investigate the distribution of phosphatidylserine (PS), a marker of cell death and platelet activation, during COVID-19.
- To assess PS as a potential marker for disease severity and immune dysfunction in COVID-19 patients.
Main Methods:
- Quantification of PS-positive blood cells and PS-positive PMPs (PS+ PMPs) in COVID-19 patients.
- Correlation analysis between PS+ PMP levels and clinical disease severity.
- Analysis of gene expression in T cells interacting with PS+ PMPs.
Main Results:
- Elevated levels of PS+ PMPs were found in COVID-19 patients for weeks post-diagnosis.
- Higher frequencies of PS+ PMP+ peripheral blood mononuclear cells (PBMCs) strongly correlated with increased disease severity.
- PS+ PMPs preferentially bound to CD8+ T cells and carried programmed death-ligand 1 (PD-L1).
Conclusions:
- PS on PMPs serves as a novel, sensitive marker for COVID-19 disease severity, outperforming existing markers.
- PS+ PMPs may contribute to immune dysfunction by affecting T cell function and promoting thromboinflammation.
- PS on activated immune cells may attract thromboinflammatory processes, exacerbating COVID-19 pathology.
