Venous thromboembolism: What to do after anticoagulation is started
ABSTRACTAfter anticoagulation has been started in patients with venous thromboembolism (VTE), three issues need to be addressed: the length of therapy, measures to help prevent postthrombotic syndrome, and a basic workup for malignancy in patients with idiopathic VTE.
KEY POINTS
- A low-molecular-weight heparin for at least 6 months is the treatment of choice for cancer-related VTE.
- We recommend 3 months of anticoagulation for VTE caused by a reversible risk factor and indefinite treatment for idiopathic VTE in patients without risk factors for bleeding who can get anticoagulation monitoring.
- Clinical factors are more important in deciding the duration of anticoagulation therapy than evidence of an inherited thrombophilic state.
- Elastic compression stockings reduce the risk of postthrombotic syndrome substantially.
- Patients with idiopathic VTE should have a basic screening for malignancy.
Deep vein thrombosis and pulmonary embolism are collectively referred to as venous thromboembolic (VTE) disease. They affect approximately 100,000 to 300,000 patients per year in the United States.1 Although patients with deep vein thrombosis can be treated as outpatients, many are admitted for the initiation of anticoagulation. Initial anticoagulation usually requires the overlap of a parenteral anticoagulant (unfractionated heparin, low-molecular-weight heparin [LMWH] or fondaparinux) with warfarin for a minimum of 5 days and until the international normalized ratio (INR) of the prothrombin time is above 2.0 for at least 24 hours.2
Three clinical issues need to be addressed after the initiation of anticoagulation for VTE:
- Determination of the length of anticoagulation with the correct anticoagulant
- Prevention of postthrombotic syndrome
- Appropriate screening for occult malignancy.
HOW LONG SHOULD VTE BE TREATED?
The duration of anticoagulation has been a matter of debate.
The risk of recurrent VTE appears related to clinical risk factors that a patient has at the time of the initial thrombotic event. An epidemiologic study3 found that patients with VTE treated for approximately 6 months had a low rate of recurrence (0% at 2 years of follow-up) if surgery was the risk factor. The risk climbed to 9% if the risk factor was nonsurgical and to 19% if there were no provoking risk factors.
The likelihood of VTE recurrence and therefore the recommended duration of treatment depend on whether the VTE event was provoked, cancer-related, recurrent, thrombophilia-related, or idiopathic. We address each of these scenarios below.
HOW LONG TO TREAT PROVOKED VTE
A VTE event is considered provoked if the patient had a clear inciting risk factor. As defined in various clinical trials, these risk factors include:
- Hospitalization with confinement to bed for 3 or more consecutive days in the last 3 months
- Surgery or general anesthesia in the last 3 months
- Immobilization for more than 7 days, regardless of the cause
- Trauma in the last 3 months
- Pregnancy
- Use of an oral contraceptive, regardless of which estrogen or progesterone analogue it contains
- Travel for more than 4 hours
- Recent childbirth.
However, the trials that tested different lengths of anticoagulation have varied markedly in how they defined provoked deep vein thrombosis.4–7
Recommendation: Warfarin or equivalent for 3 months
The American College of Chest Physicians (ACCP) recommends 3 months of anticoagulation with warfarin or another vitamin K antagonist for patients with VTE secondary to a transient (reversible) risk factor,2 and we agree.
HOW LONG TO TREAT CANCER-RELATED VTE
Patients with cancer are at higher risk of developing VTE. Furthermore, in one study,9 compared with other patients with VTE, patients with cancer were three times more likely to have another episode of VTE, with a cumulative rate of recurrence at 1 year of 21% vs 7%. Cancer patients were also twice as likely to suffer major bleeding complications while on anticoagulation.9
Warfarin is a difficult drug to manage because it has many interactions with foods, diseases, and other drugs. These difficulties are amplified in many cancer patients during chemotherapy.
Warfarin was compared with a LMWH in four randomized trials in cancer patients, and a meta-analysis10 found a 50% relative reduction in the rates of recurrent deep vein thrombosis and pulmonary embolism with LMWH treatment. These results were driven primarily by the CLOT trial (Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer),11 which showed an 8% absolute risk reduction (number needed to treat 13) without an increase in major bleeding when cancer-related VTE was treated with an LMWH—ie, dalteparin (Fragmin)—for 6 months compared with warfarin.
Current thinking suggests that VTE should be treated until the cancer is resolved. However, this hypothesis has not been adequately tested, and consequently, the ACCP gives it only a level 1C recommendation.2 The largest of the four trials comparing warfarin and an LMWH lasted only 6 months. The safety of extending LMWH treatment beyond 6 months is currently unknown but is under investigation (clinicaltrials.gov identifier NCT00942968).
