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Updated: May 14, 2026
Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Stimulation of platelet death by vancomycin
Syeda T Towhid1, Eva-Maria Schmidt, Alexander Tolios
1Department of Physiology, University of Tübingen, Germany.
Background/Aims:
Side effects of vancomycin, a widely used antibiotic, include thrombocytopenia. The vancomycin-induced thrombocytopenia has been attributed to immune reactions. At least in theory, thrombocytopenia could result in part from the triggering of apoptosis, which results in cell shrinkage and cell membrane scrambling with subsequent phosphatidylserine exposure at the cell surface. The cell membrane scrambling could be initiated by a signaling involving increase of cytosolic Ca(2+) activity, ceramide formation, mitochondrial depolarization and/or caspase activation. Vancomycin has indeed been shown to trigger neutrophil apoptosis. An effect of vancomycin on platelet apoptosis has, however, never been tested. The present study thus explored the effect of vancomycin on platelet activation and apoptosis.
Methods:
Human blood platelets were exposed to vancomycin and forward scatter was utilized to estimate cell volume, annexin V-binding to quantify phosphatidylserine (PS) exposure, Fluo-3 AM fluorescence to estimate cytosolic Ca(2+) activity ([Ca(2+)]i), antibodies to quantify ceramide formation and immunofluorescence to quantify protein abundance of active caspase-3.
Results:
A 30 minutes exposure to vancomycin (≥1 µg/ ml) decreased cell volume, triggered annexin V-binding, increased [Ca(2+)]i, activated caspase 3, stimulated ceramide formation, triggered release of thromboxane B2, and upregulated surface expression of CD62P (P-selectin) as well as activated integrin αllbβ3. Annexin V-binding and upregulation of CD62P (P-selectin) and integrin αllbβ3 was significantly blunted by removal of extracellular Ca(2+). Annexin V-binding was not significantly blunted by pan-caspase inhibitor zVAD-FMK (1 µM). In conclusion, vancomycin results in platelet activation and suicidal platelet death with increase of [Ca(2+)]i, caspase-3 activation, cell membrane scrambling and cell shrinkage. Activation and cell membrane scrambling required the presence of Ca(2+), but not activation of caspases.
Conclusion:
Vancomycin exposure leads to platelet activation and apoptosis.
Insights
Vancomycin antibiotic can cause platelet activation and apoptosis, a form of cell death. This process involves increased calcium, caspase-3 activation, and cell shrinkage, requiring calcium but not caspases.
Area of Science:
- Hematology
- Immunology
- Pharmacology
Background:
- Vancomycin, an antibiotic, is known to cause thrombocytopenia, a decrease in platelet count.
- This thrombocytopenia is thought to be immune-mediated, potentially involving platelet apoptosis.
- The effect of vancomycin on platelet apoptosis has not been previously investigated.
Purpose of the Study:
- To investigate the effect of vancomycin on platelet activation and apoptosis.
- To elucidate the mechanisms underlying vancomycin-induced platelet apoptosis.
Main Methods:
- Human platelets were exposed to vancomycin.
- Assays used included forward scatter (cell volume), annexin V-binding (phosphatidylserine exposure), Fluo-3 AM fluorescence (cytosolic Ca(2+) activity), ceramide quantification, and active caspase-3 immunofluorescence.
- Effects were assessed with and without extracellular calcium and in the presence of a caspase inhibitor.
Main Results:
- Vancomycin (≥1 µg/ml) decreased platelet volume, induced phosphatidylserine exposure, increased cytosolic Ca(2+) activity, activated caspase-3, and stimulated ceramide formation.
- Vancomycin also triggered thromboxane B2 release and upregulated surface expression of CD62P and activated integrin αllbβ3.
- These effects, particularly annexin V-binding and CD62P/integrin αllbβ3 upregulation, were blunted by calcium removal but not by a caspase inhibitor.
Conclusions:
- Vancomycin induces platelet activation and apoptosis.
- The process involves increased cytosolic Ca(2+), caspase-3 activation, cell membrane scrambling, and cell shrinkage.
- Platelet activation and membrane scrambling necessitate extracellular calcium, but caspase activation is not required.
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