Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs–induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVEC) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin consistently protected endothelial cells from CaCe-dEVs–induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.

Background/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with malignancy. Biomarkers of hypercoagulability and thromboinflammation may improve risk stratification and support personalised thromboprophylaxis, but evidence remains heterogeneous, particularly in cervical cancer. A systematic review was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Embase, and Web of Science were searched for studies published between January 2009 and March 2025 evaluating biological, molecular, genetic, and imaging biomarkers associated with hypercoagulability and thromboinflammation in women withcervical cancer. Evidence from breast cancer and broader CAT studies was incorporated to provide translational context. Owing to substantial methodological heterogeneity, findings were synthesised qualitatively. Twenty-five cervical cancer studies met eligibility criteria. D-dimer was the most extensively investigated biomarker and was consistently associated with VTE risk, although specificity was limited. Biomarkers of thrombin generation and fibrinolytic activation, including thrombin–antithrombin complexes, prothrombin fragment 1+2, and plasmin–α2-antiplasmin complex, demonstrated greater mechanistic specificity. Multimarker panels integrating coagulation, fibrinolysis, endothelial injury, platelet activation, and inflammation showed superior predictive performance compared with single biomarkers. Emerging biomarkers, including circulating tumour DNA, extracellular vesicles, and microRNAs, further supported tumour-driven thromboinflammation. SERPINE1 and F2 gene variants were associated with thrombotic risk and adverse prognosis. Current evidence supports further evaluation of integrated multimodal biomarker strategies for CAT risk assessment, but prospective, standardised, tumour-specific studies are required before biomarker-guided approaches can be implemented in clinical practice.