How I treat breakthrough thrombosis in patients with cancer

Cancer patients face an increased risk of venous thromboembolism (VTE), and breakthrough thrombosis despite anticoagulation, with a six-month cumulative incidence of 5-8%. The management of these events is clinically challenging. Confirming suspected breakthrough thrombosis requires imaging review, ideally by comparison with post-index baseline studies, as residual thrombus is common and may mimic recurrence. When true breakthrough thrombosis is confirmed, several potential contributing factors should be assessed. Tumor extension can lead to mechanical vein compression and thrombus formation. Non-adherence is common among anticoagulated patients and should be evaluated through detailed medication history. Measurement of drug-specific plasma levels, when available, may assist in confirming non-adherence. In patients on LMWH, underlying prothrombotic conditions such as heparin-induced thrombocytopenia or acquired antithrombin-deficiency must also be considered. In patients receiving oral anticoagulants, drug-drug interactions and impaired gastrointestinal absorption should be excluded. Therapeutic strategies are guided by limited evidence, primarily from observational studies. Current practice generally favors switching to therapeutic low-molecular-weight heparin (LMWH) if the patient was on oral anticoagulation, escalating LMWH dosing by 25-33% if already on therapeutic LMWH, or increasing LMWH to weight-adjusted therapeutic dose if treatment was subtherapeutic. Despite treatment adjustments, recurrence and bleeding risks remain substantial. In this review, we outline common clinical scenarios of breakthrough thrombosis in cancer patients and critically appraise the available evidence to inform treatment decisions.