ABSTRACT NUMBER: ESOC2026A1910 PROCOAGULANT PLATELETS MEDIATE CEREBRAL ARTERIAL THROMBOSIS IN CANCER

Abstract Background and aims Cancer is associated with a hypercoagulable state and an increased risk of acute ischemic stroke (AIS), contributing to poor prognosis. However, the mechanisms driving cancer-associated arterial thrombosis remain incompletely understood. Methods We studied three patient populations: active solid cancer and AIS (AIS-cancer), AIS without cancer (AIS), cancer without AIS (cancer). All participants underwent comprehensive clinical assessment, multimodal neuroimaging, and extensive blood and thrombus analyses. Platelet phenotype, circulating platelet-derived microparticles, and thrombus composition were evaluated using flow cytometry, immunohistochemistry, and scanning electron microscopy. Ex vivo experiments assessed the effects of patient plasma on platelet activation in healthy donors (HDs). Results Eighty-five patients were included (33 AIS-cancer, 32 AIS, 20 cancer). AIS-cancer patients exhibited significantly higher neutrophil counts (P = 0.033) and neutrophil-to-lymphocyte ratios (P < 0.001) compared with the other groups. No significant differences were observed in markers of systemic inflammation/endothelial activation. AIS-cancer patients showed a significant enrichment of procoagulant platelets (8.3% vs 8.0% in AIS and 9.8% in cancer), apoptotic platelets (4.0% vs 2.6% and 0.3%), and platelet-derived microparticles. Thrombi retrieved from the middle cerebral artery in AIS-cancer patients were platelet-rich and contained abundant fibrin, neutrophils (P = 0.004), and neutrophil extracellular traps, whereas thrombi from AIS patients without cancer were predominantly red blood cell-rich. Platelets within AIS-cancer thrombi displayed a pronounced pro-aggregatory and procoagulant phenotype. Consistently, plasma from AIS-cancer patients induced the formation of larger, procoagulant platelet aggregates in HD platelets ex vivo. Conclusions Procoagulant platelets play a central role in cancer-associated AIS and represent a potential therapeutic target to prevent arterial thrombosis in patients with cancer. Conflict of interest Manuela De Michele: nothing to disclose.