Venous thromboembolism (VTE) is a frequent complication in patients with cancer, especially those receiving systemic therapy in the ambulatory setting. Despite being a largely preventable condition, it remains a leading cause of morbidity and mortality in this patient population. Risk prediction models, such as the Khorana score, have been developed to stratify patients according to their underlying risk of VTE and identify those most likely to benefit from thromboprophylaxis by improving its risk-benefit ratio. Recent evidence supports the efficacy and safety of both low molecular weight heparin and direct oral anticoagulants in reducing VTE incidence in ambulatory patients with cancer who are receiving systemic therapy and are at high risk of VTE. Nevertheless, despite guideline recommendations warranting a risk-based approach, studies persistently show low adoption of thromboprophylaxis in this patient population. Barriers to implementation are complex, including clinician-, patient- and system-related factors. However, promising implementation strategies, including electronic health record integrated risk calculators, structured education programs, and patient-centered care pathways, have shown potential in improving adherence to guidelines and better clinical outcomes. This review summarizes the current evidence for thromboprophylaxis in patients with cancer, explores the challenges in translating evidence into practice, and highlights successful models designed to close the gap between guidelines and clinical practice.

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