Residual Vein Thrombosis (RVT) Establishes the Optimal Duration of Oral Anticoagulants After a First Episode of Deep Vein Thrombosis of the Lower Limbs

INTRODUCTION Long-term anticoagulant treatment with adjusted doses of vitamin K antagonists is highly effective in preventing recurrent events after a first episode of unprovoked Venous ThromboEmbolism (VTE), even if the optimal duration of this therapy is still uncertain. Since the risk of recurrency is greatest in the first year after the initial thrombotic episode and gradually diminishes thereafter, the benefit of an extended course of anticoagulant treatment may be offset over time by the persisting risk of clinically important bleeding.

A potential clinically relevant approach for establishing the optimal duration of Oral AntCoagulant Therapy (OAT) is that of predicting the individual risk for thrombotic recurrency after the index Deep Vein Thrombosis (DVT). Although the current scheme for establishing the duration of OAT is based on the nature of index DVT (idiopathic or provoked), some new data starting to select other parameters to optimize this decision. Recently, the use of D-dimer has been proven to be effective for selecting OAC duration; however, this investigation evaluated only patients with idiopathic DVT and, moreover, the use of D-dimer can not be easily handle by most of Institutions.

In earlier prospective studies conducted in patients with symptomatic DVT, the presence of a residual thrombus was associated with an increased risk of thrombotic recurrencies either in idiopathic or provoked venous thrombosis. Interestingly, recurrent events occurred not only in the previously affected veins but also in other sites, thus suggesting that Residual Vein Thrombosis (RVT) may express a pro-thrombotic status. Based on these findings, the detection of RVT may be, therefore, of help in establishing the duration of anticoagulation.

To test this hypothesis, we planned a randomized, prospective, follow-up study in patients with a first episode of symptomatic DVT treated with OAT for 3 months. Patients without RVT will not continue anticoagulation, whereas those with RVT will be randomized to either stop or resume anticoagulation.

METHODS Study patients. Patients with a first episode of documented unprovoked and provoked proximal DVT will be eligible for the study if they had completed at least three months of OAT (target INR 2.5, range 2.0-3.0). Provoked DVTs are defined as thrombotic episodes associated with pregnancy or puerperium, recent (i.e. within three months) fracture or plaster casting of a leg, immobilization with confinement to bed for three consecutive days and surgery with general anesthesia lasting longer than 30 minutes. Unprovoked DVTs are defined as thrombotic episodes occurred in apparently healthy individuals. Patients with active cancer, limited life expectancy, antiphospholipid antibody syndrome, or an other known thrombophilic status (such as antithrombin deficiency), serious liver disease, renal insufficiency (serum creatinine > 2 mg/dL), those who lived too far from the center will be excluded from the study. The study has been approved by the institutional review boards of all participating centers. All enrolled patients will provide written informed consent.