Direct evaluation of antiplatelet therapy in coronary artery disease by comprehensive image-based profiling of circulating platelets

Figures

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  Fig. 1. Comprehensive image-based profiling of circulating platelets. The experimental workflow consists of blood draw, sample preparation, high-throughput imaging, and digital image analysis. Insets show the study flow chart and the details of the digital image analysis. CAD coronary artery disease, CAG coronary angiography, PCI percutaneous coronary intervention.

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  Fig. 2. Representative histograms of platelet-related objects in CAD patients. The objective area is defined as the area of a platelet-related object (i.e., a single platelet, a platelet-platelet aggregate, or a platelet-leukocyte aggregate) in each image. Each histogram comprises 25,000 images of platelet-related objects. Insets show the representative images of platelet-related objects. ACS acute coronary syndrome, CCS chronic coronary syndrome, SAPT single antiplatelet therapy, DAPT dual antiplatelet therapy. Source data are provided as a Source Data file.

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  Fig. 3. Increased in vivo platelet aggregation observed in CAD patients. P values of each pair of adjacent classes were obtained using the two-sided Steel-Dwass test and are shown in the figure. a, b Comparison of the concentrations of circulating whole platelet aggregates and platelet-leukocyte aggregates between CAD patients (n = 207) and healthy subjects. c, d Comparison of the concentrations of circulating whole platelet aggregates and platelet-leukocyte aggregates between ACS patients (n = 42), CCS patients (n = 165), and healthy subjects. p = 1.13 × 10−10 (c) and 5.38 × 10−20 (d) with the Kruskal–Wallis test. CAD coronary artery disease, ACS acute coronary syndrome, CCS chronic coronary syndrome. Source data are provided as a Source Data file.

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  Fig. 4. Reduced in vivo platelet aggregation observed in CAD patients following antiplatelet therapy. P values of each pair of adjacent classes were obtained using the two-sided Steel-Dwass test and are shown in the figure. a, b Effect of antithrombotic therapy on the concentrations of circulating whole platelet aggregates and platelet-leukocyte aggregates in CAD patients (n = 28 for no drug, n = 68 for one drug administered, n = 111 for two or more drugs administered). p = 2.82 × 10−4 (a) and 1.23 × 10−3 (b) with the Kruskal–Wallis test. c, d Effect of antiplatelet therapy on the concentrations of circulating whole platelet aggregates and platelet-leukocyte aggregates in CAD patients (n = 38 for no therapy, n = 73 for SAPT, n = 96 for DAPT). p = 1.30 × 10−3 (c) and 3.84 × 10−3 (d) with the Kruskal–Wallis test. e, f Effect of antiplatelet therapy on the concentrations of circulating whole platelet aggregates and platelet-leukocyte aggregates in CAD patients who did not receive anticoagulant therapy (n = 28 for no therapy, n = 58 for SAPT, n = 89 for DAPT). p = 3.09 × 10−4 (e) and 9.16 × 10−4 (f) with the Kruskal–Wallis test. IQR interquartile range, SAPT single antiplatelet therapy, DAPT…

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  Fig. 5. Comparison of in vivo platelet aggregation levels across different blood sampling sites in CAD patients. a–c Associations between the concentrations of circulating whole platelet aggregates in the peripheral artery, coronary artery, and vein in CAD patients (n = 129). d–f Associations between the concentrations of circulating whole platelet aggregates in the peripheral artery, coronary artery, and vein in CAD patients (n = 36) on the day of catheterization. P values were obtained using the one-sided F test and are shown in the figure. Source data are provided as a Source Data file.

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  Fig. 6. Longitudinal assessment of the effect of antiplatelet therapy on in vivo platelet aggregation in CAD patients. a, b Patients diagnosed with CCS and treated with SAPT before undergoing PCI procedures. c, d Patients diagnosed with ACS undergoing an emergency PCI procedure and a staged PCI procedure. ACS acute coronary syndrome, CCS chronic coronary syndrome, SAPT single antiplatelet therapy, DAPT dual antiplatelet therapy, PCI percutaneous coronary intervention. Source data are provided as a Source Data file.