How I treat breakthrough thrombosis in patients with cancer

Patients with cancer face an increased risk of venous thromboembolism (VTE), and breakthrough thrombosis despite anticoagulation, with a 6-month cumulative incidence of 5% to 8%. The management of these events is challenging. Confirming suspected breakthrough thrombosis requires imaging review, ideally by comparison with postindex baseline studies, because residual thrombus is common and may mimic recurrence. When breakthrough thrombosis is confirmed, several potential contributing factors should be assessed. Nonadherence is common among patients undergoing anticoagulation and should be evaluated through detailed medication history. Measurement of drug-specific plasma levels, when available, may assist in confirming nonadherence. In patients on low-molecular-weight heparin (LMWH), underlying prothrombotic conditions such as heparin-induced thrombocytopenia or acquired antithrombin deficiency must also be considered. For 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 LMWH if the patient was on oral anticoagulation, escalating LMWH dosing by 25% to 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 patients with cancer and critically appraise the available evidence to inform treatment decisions.