What is the role of long-term anticoagulation in the treatment of deep venous thrombosis (DVT)?

Updated: Nov 09, 2018
  • Author: Donald Schreiber, MD, CM; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
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Answer

Answer

Long-term anticoagulation is necessary to prevent the high frequency of recurrent venous thrombosis or thromboembolic events. Interruption of anticoagulation within the first 12 weeks of therapy appears to result in a 25% incidence of recurrent thrombosis. [8] Oral vitamin K antagonists (VKAs) (warfarin) remain the preferred approach for long-term treatment, which allows for single-dosing oral therapy that can be continued on an outpatient basis.

The American College of Chest Physicians (ACCP) recommends cessation of anticoagulant therapy after 3 months of treatment in those with (1) surgery-associated acute proximal deep venous thrombosis (DVT), (2) an acute proximal DVT or pulmonary embolism (PE) provoked by a nonsurgical transient risk factor, and (3) a first unprovoked VTE and a high risk of bleeding. [3] (In those with a low or moderate bleeding risk, extend anticoagulation without a scheduled stop date.) [3]

When the risk of venous thromboembolism (VTE) recurrence is high in patients with subsegmental PE without DVT, the ACCP recommends anticoagulation over surveillance; when the VTE recurrence risk is low in these patients, surveillance over anticoagulation is suggested. [3]

Barring contraindications to aspirin therapy, aspirin is recommended to prevent recurrent VTE in patients with an unprovoked proximal DVT or PE following anticoagulation cessation. [3]

Warfarin interrupts the production of vitamin K–dependent coagulation factor production by the liver. The effect is delayed by 72 hours until the existing circulating coagulation factors are cleared or used. The initial effect creates a hypercoagulable state because vitamin K–dependent anticoagulants (protein C and S) are cleared first from the body while vitamin K–dependent procoagulants continue to circulate. During this period, heparin anticoagulation is important to prevent worsening thrombosis. An international normalized ratio (INR) maintenance at 2-3 is recommended; higher ratios do not improve effectiveness, and lower ratios do not reduce bleeding complications. [10, 29]

The duration of therapy with warfarin has been evaluated by multiple prospective, randomized clinical trials. [8, 30, 31] Duration of therapy varies depending on patient risk factors and presumed etiology. A first-episode venous thrombosis or thrombotic event due to a transient reversible risk factor should be treated for at least 3 months. Interruption of therapy prior to 12 weeks results in an 8% absolute increase in recurrent thrombosis within the following 12 months. Treatment for the entire 3 months results in an annual recurrent DVT incidence of 3%.

Approval of factor Xa inhibitors (eg, rivaroxaban, apixaban) and direct thrombin inhibitors (eg, dabigatran) for prevention of recurrent DVT following initial therapy allows for more therapeutic options for long-term anticoagulation.

For patients with first-episode idiopathic venous thrombosis, treatment length should be 6-12 months. [8] However, the benefit of anticoagulation is lost after stopping treatment at 1 year, prompting many physicians to continue treatment indefinitely. [32] The decision to continue anticoagulation should be tailored to each patient, taking into consideration bleeding risk and patient preference, with treatment reassessment at periodic intervals.

For patients with a first-episode venous thrombosis and documented antiphospholipid antibodies or two or more thrombophilic conditions (combined factor V Leiden and prothrombin 20210A gene mutations), at least 12 months of treatment is indicated. Six to 12 months of initial therapy is indicated in those patients with any one of the following: deficiencies of antithrombin, protein C, or protein S; factor V Leiden; prothrombin 20210A; hyperhomocysteinemia; or high factor VIII levels (>90th percentile). Indefinite therapy is also considered in both of these patient populations. [8]


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