Venous Thromboembolism (VTE) is a vexing heterogeneous disease that, along with Myocardial Infarction (MI) and stroke, is among the top three cardiovascular killers. VTE's morbidity and mortality globally cause high social, health, and economic impacts. The modern diagnostic strategies of Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) developed to aid physicians in diagnosing these presentations and using imaging resources effectively have shown limitations in several subgroups, including patients with recurrent VTE or those who are already on anticoagulation therapy. In the light of a previously reported breakthrough (recurrent) DVT while on rivaroxaban 20 mg PO daily in a 43-year-old Caucasian female, this review discusses the various etiologies, which contribute to anticoagulant's failure and VTE's recurrences in general to increase awareness among practicing physicians about these subgroups. The roles of imaging and D-dimer testing in these subgroups are also discussed, leading the author to cautiously conclude that diagnostic imaging plays a central role in identifying recurrence regardless of D-dimer testing and recommending baseline sonography upon completing DVT anticoagulation therapy for future references. Accurate diagnostic strategies are needed to ensure the best available care and treatment reaches the patient. Based on this review, the author constructs a hypothetical algorithm targeted to diagnose recurrent VTE or breakthrough VTE while on anticoagulants coupled with the possible causes for recurrent and breakthrough VTE. This algorithm should only be considered as hypothesis-generating for specifically designed prospective studies to assess and validate the algorithm's potential in decreasing the incidence of missed diagnosis of VTE and their underlying etiologies in these subgroups.
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