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Updated: Jun 5, 2026
Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
The septic milieu triggers expression of spliced tissue factor mRNA in human platelets
M T Rondina1, H Schwertz, E S Harris
1Division of General Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. matthew.rondina@hsc.utah.edu
Background:
Activated platelets have previously-unrecognized mechanisms of post-transcriptional gene expression that may influence hemostasis and inflammation. A novel pathway involves splicing of pre-mRNAs in resting platelets to mature, translatable mRNAs in response to cellular activation.
Objectives:
We asked if bacterial products and host agonists present in the septic milieu induce tissue factor pre-mRNA splicing in platelets from healthy subjects. In parallel, we asked if spliced tissue factor (TF) mRNA is present in platelets from septic patients in a proof-of-principle analysis.
Patients/Methods:
TF pre-mRNA and mRNA expression patterns were characterized in platelets from septic patients and in platelets isolated from healthy subjects activated with bacteria, toxins and inflammatory agonists. Procoagulant activity was also measured.
Results And Conclusions:
Live bacteria, staphylococcal α-toxin and lipopolysaccharide (LPS) induced TF pre-mRNA splicing in platelets isolated from healthy subjects. Toxin-stimulated platelets accelerated plasma clotting, a response that was blocked by a previously-characterized splicing inhibitor and by an anti-tissue factor antibody. Platelets from septic patients expressed spliced TF mRNA, whereas it was absent from unselected and age-matched control subjects. Tissue factor-dependent procoagulant activity was elevated in platelets from a subset of septic patients. Thus, bacterial and host factors induce splicing of TF pre-mRNA, expression of TF mRNA and tissue factor-dependent clotting activity in human platelets. TF mRNA is present in platelets from some septic patients, indicating that it may be a marker of altered platelet phenotype and function in sepsis and that splicing pathways are induced in this syndrome.
Insights
Bacterial and host factors trigger tissue factor (TF) pre-mRNA splicing in platelets, leading to TF mRNA expression and increased clotting. This TF mRNA is present in platelets of septic patients, suggesting altered platelet function in sepsis.
Area of Science:
- Platelet biology
- Molecular mechanisms of gene expression
- Sepsis and inflammation
Background:
- Platelets possess uncharacterized post-transcriptional gene expression mechanisms influencing hemostasis and inflammation.
- A novel pathway involves pre-messenger RNA (pre-mRNA) splicing in resting platelets to mature, translatable messenger RNAs (mRNAs) upon activation.
Purpose of the Study:
- To investigate if bacterial products and host agonists induce tissue factor (TF) pre-mRNA splicing in healthy platelets.
- To determine if spliced TF mRNA is present in platelets from septic patients.
Main Methods:
- Characterization of TF pre-mRNA and mRNA expression in platelets from septic patients.
- Analysis of platelets from healthy subjects activated with bacteria, toxins, and inflammatory agonists.
- Measurement of procoagulant activity.
Main Results:
- Live bacteria, staphylococcal α-toxin, and lipopolysaccharide (LPS) induced TF pre-mRNA splicing in healthy platelets.
- Toxin-stimulated platelets accelerated plasma clotting, an effect inhibited by a splicing inhibitor and anti-TF antibody.
- Spliced TF mRNA was found in platelets from septic patients but not in control subjects.
- Elevated TF-dependent procoagulant activity was observed in platelets from some septic patients.
Conclusions:
- Bacterial and host factors induce TF pre-mRNA splicing, TF mRNA expression, and TF-dependent clotting activity in human platelets.
- The presence of TF mRNA in septic patient platelets suggests it may serve as a marker of altered platelet phenotype and function in sepsis.
- Splicing pathways are activated in human platelets during sepsis.
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