Abstract

Arterial thrombosis, which represents a critical complication of cardiovascular diseases, is a leading cause of death and disability worldwide. A symbolic feature of arterial thrombosis is large-scale platelet aggregation due to high shear stress generated by stenosis. However, current hematological tests cannot evaluate arterial thrombosis in such physiological settings. To bridge this gap, we developed a microfluidics-based thrombus profiling assay (Fig. 1A) that combines multi-fluorescence imaging with a stenotic channel design to comprehensively characterize thrombi formed in high shear blood flow (Fig. 1B, C). Thrombi are characterized by a 7-dimensional profile indicating the thrombus size (Plt) and levels of fibrinogen (Fg), VWF, P-selectin, phosphatidylserine (PS) and extended (E + ) and activated α IIb β 3 in the thrombus (Fig. 1D). Using this assay, we discovered intensified thrombus formation in subjects with hypertension and/or aging (Fig. 1D). We also found extended integrin α IIb β 3 as a superior biomarker for platelet hyperreactivity than P-selectin and activated integrin α IIb β 3 and a potential predictor for arterial thrombosis (Fig. 1E). By studying the effects of anti-thrombotic agents NMC4 and 7E3 on hypertension patients’ blood, our work reveals a ‘treatment mismatch’ phenomenon that can seriously affect the efficacy and safety of anti-thrombotic drugs (Fig. 1F). Our findings provide mechanistic insights into the high risk of arterial thrombosis and antiplatelet resistance in populations with hypertension and aging. The discovered ‘treatment mismatch’ heralds a new era in thrombosis management where patients’ thrombus profiles dictate personalized therapeutic decisions to optimize treatment efficacy and reduce adverse outcomes. The outstanding performance of our assay underscores its translational potential for anti-thrombotic drug screening, thrombosis diagnosis, and personalized anti-thrombotic regimen selection.