Decision Making in Venous Thromboembolism

In many patients who are clinically stable without significant medical comorbidities, outpatient administration of these medications without hospitalization is considered safe. Patients with DVT are often safe to manage as outpatients unless significant clot burden is present and thrombolysis is being considered. For PE, the pulmonary embolism severity index (PESI) and simplified index (sPESI) may be useful to risk-stratify patients and identify those at low risk of complications who may be suitable for outpatient treatment [59,60].Studies have shown that hemodynamically stable patients who did not require supplemental oxygenation or have contraindications to LMWH therapy were safely managed as outpatients with low risk of recurrent VTE and bleeding [61,62].One exception may be patients with intermediate risk PE, who are hemodynamically stable but have evidence of right ventricular dysfunction and may be better served by an initial in-hospital observation period, especially if thrombolysis is being considered.

Most patients who present with VTE are transitioned to warfarin for long-term therapy. Warfarin can be started on the same day as parenteral anticoagulation. Both drugs are overlapped for at least 5 days, with a target INR of 2.0–3.0. Patients may achieve the target INR level quickly because factor VII has a short half-life and the level drops quickly; however, the overlap of 5 days is essential even when the INR is in the target range because a full anticoagulant affect is not achieved until prothrombin levels decline, and this is a slow process due to the long half-life of prothrombin. Warfarin also causes rapid decrease in levels of natural anticoagulants such as protein C and protein S, which further exacerbates the net hypercoagulable state in the short-term. Warfarin without a bridging parenteral agent carries a risk of warfarin-induced skin necrosis [63]and is not effective as an initial anticoagulant treatment in acute VTE as there is a relatively high risk of symptomatic clot extension or recurrent VTE compared to warfarin with use of a bridging agent [64].In specific cases such as cancer-associated VTE (see discussion below), LMWH is preferred to warfarin for long-term active therapy.

Long-Term Active Therapy After Acute Treatment

Duration of Anticoagulation

Recommended duration of anticoagulation depends on a myriad of factors including severity of VTE, risk of recurrence, bleeding risk, and lifestyle modification issues, as well as on the safety and availability of alternative therapies such as low-intensity warfarin, aspirin, or the new oral anticoagulants. The decision tree for length of treatment starts with whether the VTE was a provoked or a spontaneous event. Provoked events occur when the event is associated with an identifiable risk factor, such as immobilization from prolonged medical illness or surgical intervention, pregnancy or oral contraceptive use, and prolonged air travel.

Consensus guidelines suggest that 3 months of anti-coagulation are generally sufficient treatment for a provoked VTE [51,65,66]. Data from multiple studies and a meta-analysis suggests that less than 3 months of anticoagulation (4 to 6 weeks in most trials) is associated with an approximately 1.5-fold higher risk of recurrent VTE than 3 months [67,68].However, data from this meta-analysis also suggests that anticoagulation for longer than 3 months (6 to 12 months in most trials) is not associated with higher rates of recurrent VTE. We generally anticoagulate for 3 months in patients with provoked VTE.