Red Blood Cell Biomechanics and Cancer-Associated Thrombosis

Cancer-associated thrombosis (CAT) remains a leading cause of morbidity and mortality in oncology, reflecting the convergence of tumor-driven hypercoagulability, endothelial dysfunction, and venous stasis. While current models of CAT pathogenesis emphasize tumor-derived procoagulant factors, platelets, and leukocytes, the contribution of red blood cell (RBC) biomechanics has received comparatively limited attention. Emerging evidence indicates that both malignancy and cancer-related therapies impair RBC deformability and increase RBC aggregation; alterations that are known to influence blood viscosity, platelet margination, microvascular flow, and clot contraction. Hence, these alterations have been hypothesized to promote thrombosis, supported by evidence of increased thrombosis risk in diseases that primarily affect RBC biomechanics. While cancer-induced alterations in RBC biomechanics and their role in thrombosis are well-described in non-cancerous conditions, the relationship between altered RBC biomechanics and thrombosis in the setting of cancer has not been thoroughly investigated. Accordingly, this review synthesizes the mechanistic and clinical data linking altered RBC biomechanics to thrombus initiation, propagation, and stability, with particular emphasis on their relationship with established cancer-related prothrombotic pathways such as extracellular vesicle release, neutrophil extracellular trap formation, stasis, and oxidative stress. Finally, we critically assess current CAT risk assessment models (RAM) and discuss the potential role of RBC biomechanical parameters as dynamic, integrative biomarkers to improve thrombosis risk stratification in cancer patients. Advances in automated and standardized rheological technologies may facilitate the clinical translation of RBC biomechanics, offering new opportunities to refine risk prediction and deepen mechanistic understanding of CAT.