Recurrent Venous Thromboembolism During Anticoagulation: Diagnosis, Systematic Evaluation, and Management

TOPIC IMPORTANCE Recurrent venous thromboembolism (rVTE) occurring during therapeutic anticoagulation represents a clinically challenging and high-risk condition. REVIEW FINDINGS Although the incidence of breakthrough events under adequate anticoagulant therapy is relatively low, their occurrence is associated with increased short-term mortality, heightened bleeding risk related to treatment escalation, and long-term morbidity. Accurate diagnosis is critical and should rely on careful comparison with prior imaging studies. Residual thrombosis and early clot propagation are relatively frequent findings during follow-up and may mimic true recurrence, leading to potential misclassification. Management of rVTE during anticoagulation is largely informed by observational studies, guideline recommendations, and expert consensus, as robust randomized trial data are lacking. A structured approach is essential and should begin with confirmation of adherence, appropriate dosing, drug-drug interactions and possible absorption issues. Targeted evaluation for underlying prothrombotic conditions, including malignancy and antiphospholipid syndrome, is recommended. Low-molecular-weight heparin (LMWH) remains central to acute management, although supporting evidence is limited. Special populations require individualized strategies balancing thrombotic and bleeding risks. Routine use of inferior vena cava filters should be avoided, and intensified anticoagulation should generally be time-limited with planned reassessment. SUMMARY Significant gaps remain in the evidence base. Prospective registries and well-designed randomized trials are needed to refine diagnostic criteria, clarify mechanisms of anticoagulant failure, and define optimal management strategies in this high-risk population.