Related Experiment Video
Updated: Dec 14, 2025
Analyzing Platelet Subpopulations by Multi-color Flow Cytometry
Published on: June 10, 2025
Sex differences in flow cytometry-based platelet reactivity in stable outpatients suspected of myocardial ischemia
Farahnaz Waissi1,2, Mirthe Dekker1,2, Ingrid E M Bank3,4
1Department of Vascular Surgery University Medical Center Utrecht Utrecht The Netherlands.
Insights
Women exhibit higher platelet reactivity than men, potentially impacting antiplatelet therapy effectiveness. Further research is needed on P2Y12 inhibitors in women with suspected myocardial ischemia.
Area of Science:
- Cardiovascular Medicine
- Platelet Biology
- Pharmacology
Background:
- Antiplatelet therapy is crucial for secondary cardiovascular event prevention.
- Existing research suggests women may not benefit equally from antiplatelet therapies compared to men.
- The influence of sex-based differences in platelet biology on antiplatelet response remains unclear.
Purpose of the Study:
- To investigate sex differences in platelet reactivity among outpatients with chest pain.
- To assess the impact of these differences on response to antiplatelet agents.
Main Methods:
- A cohort of 382 outpatients with suspected myocardial ischemia (MYOMARKER study) was analyzed.
- Platelet reactivity was measured using flow cytometry, assessing degranulation (P-selectin) and aggregation (fibrinogen binding).
- Activation was induced by protease activating receptor 1-activating peptide (PAR1-AP) and adenosine 5'-phosphate (ADP).
Main Results:
- Women showed higher platelet reactivity than men upon stimulation with PAR1-AP and ADP.
- P2Y12 inhibitor use significantly reduced fibrinogen binding but had a minor effect on P-selectin expression.
- Women using P2Y12 inhibitors demonstrated less inhibition of fibrinogen binding to PAR1-AP compared to men.
Conclusions:
- Sex differences in platelet reactivity warrant further investigation in the context of antiplatelet therapy.
- Differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia require additional study.
Background:
Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents.
Methods:
Platelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry-based platelet activation test that quantifies both platelet degranulation (P-selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbβ3) in whole blood.
Results:
Platelet reactivity was higher in women compared with men when activated with protease activating receptor 1-activating peptide SFLLRN (PAR1-AP) and adenosine 5'-phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1-AP, but only slightly reduced platelet P-selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1-AP stimulation than men (n = 38) using P2Y12 inhibitors.
Conclusions:
These findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia.
