Burst-like Secretion of Platelet Dense Granules Promotes Thrombus Shell Expansion

Vessel-wall injury triggers platelet recruitment and aggregation with exquisite spatiotemporal regulation. While secreted agonists from thrombin-activated platelets play a crucial role in thrombus formation, the underlying mechanisms remain elusive. Using real-time imaging of isolated human platelets, we demonstrate that dense granules, which are enriched with agonists, are released in brief, stochastic bursts driven by intracellular calcium spikes, which are necessary but not individually sufficient to trigger secretion events. This burst-like secretion is sustained through extracellular feedback, establishing a cooperative, probabilistic mechanism of granule release in which released agonists amplify thrombin-induced granule exocytosis and increase the likelihood of secretion bursts. Computational modeling of whole-thrombus growth reveals that these transient bursts generate localized microdomains of high agonist concentration, facilitating expansion of the outer thrombus layers. Our findings establish burst-like secretion as a distinct hemostatic mechanism that enhances platelet recruitment and orchestrates thrombus architecture through localized, self-reinforcing activation. Key pointsO_LILive imaging reveals dense granules secretion in discrete bursts. C_LIO_LIIntracellular calcium spikes are necessary but not sufficient for triggering secretion events. C_LIO_LIBurst-like secretion arises from cooperativity, driven by the feedback amplification from the extracellularly released granule content. C_LIO_LIBurst-like dense granule secretion promotes dynamic expansion of the thrombus shell in silico. C_LI