Personalized Anticoagulation in Cancer Patients: Current Evidence and Future Perspectives

Background and Objectives: Cancer-associated thrombosis (CAT) is still a leading cause of morbidity and mortality in patients with malignancy and represents a major challenge in cardio-oncology. Although low-molecular-weight heparins (LMWH) have long been the standard of care, direct oral anticoagulants (DOACs) have broadened treatment options. However, balancing thrombotic and bleeding risks, accounting for tumor- and individual-specific characteristics, requires an individualized therapeutic approach. This review summarizes current evidence supporting personalized anticoagulation strategies in CAT. Materials and Methods: A structured narrative review supported by a systematic literature search was conducted. Evidence regarding LMWH, DOACs, and emerging factor XI/XIa inhibitors was critically appraised, with emphasis on clinical scenarios necessitating individualized management, including gastrointestinal, genitourinary, and intracranial malignancies, hepatocellular carcinoma, thrombocytopenia, renal impairment, drug-drug interactions, and recurrent thrombosis. Results: Both LMWH and DOACs are effective options for CAT, with treatment selection guided by the balance between thrombotic and bleeding risks. Among DOACs, apixaban appears to have a favorable efficacy-safety profile based on current evidence, whereas rivaroxaban and edoxaban remain suitable for carefully selected patients despite higher bleeding risk in specific settings. LMWH continues to be preferred in patients with active mucosal tumors, severe thrombocytopenia, advanced renal dysfunction, significant drug-drug interactions, or when dosing flexibility is required. Emerging evidence also points to possible pleiotropic effects of DOACs on inflammation, angiogenesis, and metastatic progression, although the results have not yet translated into proven clinical benefit. Factor XI/XIa inhibitors remain investigational, with no established role in cancer-associated thrombosis. Conclusions: Contemporary CAT management has shifted toward personalized anticoagulant selection based on tumor characteristics, bleeding risk, organ function, anticancer therapy, and patient-related factors. Future advances, including factor XI/XIa inhibitors and a better understanding of anticoagulants' biological effects beyond thrombosis prevention, may further optimize individualized treatment and improve clinical outcomes.