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Updated: May 4, 2026
Analyzing Platelet Subpopulations by Multi-color Flow Cytometry
Published on: June 10, 2025
The relationship between fractional flow reserve, platelet reactivity and platelet leukocyte complexes in stable
Jan-Willem E M Sels1, Bert Rutten2, Thijs C van Holten2
1Department of Cardiology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands ; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Insights
Patients with significant coronary artery stenosis show normal platelet reactivity but reduced platelet-neutrophil complexes. This finding impacts understanding stable coronary artery disease prognosis and platelet activation markers.
Area of Science:
- Cardiovascular Science
- Hematology
- Medical Diagnostics
Background:
- Significant coronary artery stenoses impair blood flow, causing myocardial ischemia and negatively impacting stable coronary artery disease (CAD) prognosis.
- Altered platelet reactivity is linked to poorer outcomes in stable CAD.
- Platelets activate and form complexes with leukocytes due to shear stress from blood flow dynamics.
Purpose of the Study:
- To investigate the association between hemodynamically significant coronary stenoses and altered platelet reactivity.
- To examine the formation of platelet-leukocyte complexes in patients with stable CAD and flow-limiting stenoses.
Main Methods:
- One hundred stable angina patients were assessed using Fractional Flow Reserve (FFR) to determine stenosis significance.
- Whole blood samples were analyzed via flow cytometry for platelet activation (P-selectin) and platelet-leukocyte complexes after stimulation.
- Patients were stratified based on FFR results (FFR-positive vs. FFR-negative) and clopidogrel use.
Main Results:
- No significant difference in overall platelet reactivity was observed between FFR-positive and FFR-negative patients.
- A statistically significant reduction in circulating platelet-neutrophil complexes was found in FFR-positive patients.
- A non-significant trend towards decreased platelet-monocyte complexes was noted in FFR-positive individuals.
Conclusions:
- Hemodynamically significant coronary stenoses do not alter intrinsic platelet reactivity.
- Reduced platelet-neutrophil complexes in peripheral blood are associated with significant coronary stenoses in stable CAD patients.
Background:
The presence of stenoses that significantly impair blood flow and cause myocardial ischemia negatively affects prognosis of patients with stable coronary artery disease. Altered platelet reactivity has been associated with impaired prognosis of stable coronary artery disease. Platelets are activated and form complexes with leukocytes in response to microshear gradients caused by friction forces on the arterial wall or flow separation. We hypothesized that the presence of significantly flow-limiting stenoses is associated with altered platelet reactivity and formation of platelet-leukocyte complexes.
Methods:
One hundred patients with stable angina were studied. Hemodynamic significance of all coronary stenoses was assessed with Fractional Flow Reserve (FFR). Patients were classified FFR-positive (at least one lesion with FFR≤0.75) or FFR-negative (all lesions FFR>0.80). Whole blood samples were stimulated with increasing concentrations of ADP, TRAP, CRP and Iloprost with substimulatory ADP. Expression of P-selectin as platelet activation marker and platelet-leukocyte complexes were measured by flowcytometry. Patients were stratified on clopidogrel use. FFR positive and negative patient groups were compared on platelet reactivity and platelet-leukocyte complexes.
Results:
Platelet reactivity between FFR-positive patients and FFR-negative patients did not differ. A significantly lower percentage of circulating platelet-neutrophil complexes in FFR-positive patients and a similar non-significant decrease in percentage of circulating platelet-monocyte complexes in FFR-positive patients was observed.
Conclusion:
The presence of hemodynamically significant coronary stenoses does not alter platelet reactivity but is associated with reduced platelet-neutrophil complexes in peripheral blood of patients with stable coronary artery disease.
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