Understanding clot composition in cancer-associated thromboembolism

Cancer represents a major clinical challenge, also due to its substantial burden of vascular complications. Cancer-associated vascular occlusions, including ischaemic stroke, arise from the combined influence of diverse clinical and biological drivers. The intensity and relative contribution of these mechanisms vary across tumour types and disease stages and can ultimately shape clot composition. In this narrative review, we summarize the principal clinical and biological determinants that promote vascular occlusions in cancer, examine the available literature on the cellular and molecular composition of cancer-associated clots in stroke, and highlight gaps and emerging directions in clot composition studies. Histopathological studies indicate that cerebral arterial clots retrieved from patients with active cancer tend to exhibit a platelet- and fibrin-enriched architecture, with a relative reduction in erythrocyte content compared with non-cancer stroke controls. Importantly, a growing body of case reports and small series has demonstrated that tumour cells or tumour fragments can be identified within retrieved cerebral arterial clots of cancer patients with stroke. Conversely, inflammatory signatures within cancer-related thrombi remain less characterized. A better understanding of clot composition in cancer patients might have important implications for refining the understanding of cancer-associated vascular events and guiding future diagnostic and treatment strategies.