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Updated: Jan 8, 2026
Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
Tissue Factor, a Membrane-associated Marker of Platelet Activation, Predicts 5-year Cardiovascular Mortality in
Marina Camera1,2, Marta Brambilla2, Nicola Cosentino2
1Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy.
Insights
Tissue factor-positive (TFpos) platelets predict mortality in coronary artery disease (CAD) patients. Elevated TFpos platelets indicate a higher risk for all-cause and cardiovascular death, even in patients on antiplatelet therapy.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Thrombosis Research
Background:
- Coronary artery disease (CAD) patients exhibit heightened platelet activation, yet the prognostic significance of this activation remains under-investigated.
- Effective risk stratification for thrombotic events in CAD is a critical unmet clinical need.
Purpose of the Study:
- To evaluate the prognostic value of platelet activation markers, specifically tissue factor (TF)-positive (TFpos) platelets, in predicting mortality among CAD patients.
- To determine if TFpos platelet levels can improve risk prediction beyond established clinical models.
Main Methods:
- Whole-blood flow cytometry and ELISA were used to analyze platelet activation markers in 527 CAD patients (acute coronary syndromes [ACS] and chronic coronary syndrome [CCS]).
- Five-year survival analysis using COX regression models assessed all-cause (AC) and cardiovascular (CV) mortality.
- Optimal cut-off values for TFpos platelets were determined using the Euclidean distance method.
Main Results:
- Elevated TFpos platelets (>4%) independently predicted both AC and CV mortality in CAD patients.
- Patients with >4% TFpos platelets exhibited significantly higher AC and CV mortality rates compared to those with <4% TFpos platelets.
- TFpos platelet levels improved cardiovascular mortality prediction in patients on dual antiplatelet therapy, outperforming a standard clinical model.
Conclusions:
- The percentage of circulating TFpos platelets serves as an independent predictor of all-cause and cardiovascular mortality in CAD patients.
- TFpos platelet measurement offers a valuable tool for risk stratification in CAD patients, including those receiving antiplatelet therapy.
Abstract:
Thrombotic risk stratification in coronary artery disease (CAD) patients is an unmet need. CAD patients show increased platelet activation, but its prognostic relevance remains unexplored. We aimed to assess the prognostic value of platelet-activation markers on mortality in CAD patients.Surface expression of platelet-associated activated GPIIbIIIa, P-selectin, tissue factor (TF), and platelet-leukocyte aggregate was analyzed in 527 CAD patients (acute coronary syndromes [ACS, n = 149] and chronic coronary syndrome [CCS, n = 378]) by whole-blood flow-cytometry and plasma F1 + 2 by ELISA. With COX regression model 5-year survival analysis from all-cause (AC) and cardiovascular (CV) mortality was performed. Cross-validated cut-off of TFpos platelets was calculated by Euclidean distance method.AC and CV mortality rates were 9.7 and 6.5%, respectively. Among the biomarkers evaluated, only TF independently predicted AC mortality (hazard ratio [HR] =2.02, p = 0.042) also after adjustment for CAD presentation. ACS and CCS patients with TFpos platelets >4% (the best cut-off value for all-cause mortality prediction) had the highest levels of F1 + 2 and a worse prognosis for AC and CV mortality (HR = 1.91; p = 0.018 and HR = 2.51; p = 0.005; respectively) than those with <4% TFpos platelets. Interestingly, patients on dual antiplatelet therapy (n = 246, 46.8%) responder to P2Y12 inhibitors with TFpos platelets >4% had the highest risk for AC mortality (HR = 4.11; p = 0.0215) and CV mortality (HR = 6.88; p = 0.0408). In these patients, TFpos platelet levels outperformed a clinical model in CV mortality prediction (net reclassification improvement = 0.436, p < 0.001). Platelet TF predicted AC (HR = 3.03; p = 0.012) and CV mortality (HR = 3.56; p = 0.008) in aspirin-only treated patients also (n = 239, 45.3%).The percentage of circulating TFpos platelets may serve as an independent predictor of AC and CV mortality in CAD patients on antiplatelet therapy.
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