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.
SCREENING FOR OCCULT MALIGNANCY
VTE can be the first manifestation of cancer.
French physician Armand Trousseau, in the 1860s, was the first to describe disseminated intravascular coagulation closely associated with adenocarcinoma. Ironically, several years later, after suffering for weeks from abdominal pain, he declared to one of his students that he had developed thrombosis, and he died of gastric cancer shortly thereafter.47
Since cancer is a well-known risk factor for VTE, it is logical to screen for cancer as an explanation for an idiopathic VTE event.48 To make an informed decision, one needs to understand the rate of occult cancer at the time VTE is diagnosed, the risk of future development of cancer, and the utility of extensive cancer screening.
The clinical efficacy, side effects, and cost-effectiveness of cancer screening in patients with idiopathic VTE are unknown. However, a systematic review47 of 34 studies found that, in patients with idiopathic VTE, cancer was diagnosed within 1 month in 6.1%, within 6 months in 8.6%, and within 1 year in 10.0% (95% CI 8.6–11.3).
A subset of studies compared two strategies for screening soon after the diagnosis of idiopathic VTE: a strategy limited to the history, physical examination, basic blood work, and chest radiography vs an extensive screening strategy that also included serum tumor markers or abdominal ultrasonography or computed tomography. Limited screening detected 49% of the prevalent cancers; extensive screening increased this rate to 70%. Stated another way, the detection rate for prevalent cancers was 5% with limited screening and 7% with extensive screening soon after the diagnosis of idiopathic VTE.47
Patients with idiopathic VTE had higher rates of cancer within 1 month of diagnosis than patients with provoked VTE (6.1% vs 1.9%), and this difference persisted at 1 year (10.0% vs 2.6%).47
Recommendation: Individualized cancer screening
Patients with idiopathic VTE have a significant risk of occult cancer within the first year after diagnosis, and cancer screening should be considered. Our practice for patients with idiopathic VTE is to perform a history and physical examination and ensure that the patient is up to date on age- and sex-specific cancer screening.
The use of additional imaging or biomarkers should be discussed with patients so they can balance the risks (radiation and potential false-positive results with their downstream consequences), costs, and potential benefits, given the lack of proven survival benefit or cost-effectiveness.
ORAL ANTICOAGULANT MANAGEMENT
Warfarin’s multiple interactions, along with the need for INR monitoring, make it a difficult medication to manage.
The Joint Commission, the US organization for health service accreditation and certification, has defined National Patient Safety Goals and quality measures for the management of anticoagulation.49 Organized anticoagulation management services, dosing algorithms, and patient self-testing using capillary INR meters or patient self-management of warfarin were recommended as tools to improve the time patients spend in the therapeutic INR range.50
Two new oral anticoagulants
The limitations of warfarin have stimulated the search for newer oral anticoagulants that do not require laboratory monitoring or have as many diet and drug interactions.
Two trials have been published with experimental oral anticoagulants that had similar efficacy and safety as warfarin in the treatment of VTE.
The study of dabigatran (Pradaxa) vs warfarin in the treatment of acute VTE (the RECOVER trial)51 randomized 2,539 patients with acute VTE to receive the oral direct thrombin inhibitor dabigatran or warfarin for approximately 6 months. Of note, each treatment group received a median of 6 days of heparin, LMWH, or fondaparinux at the beginning of blinded therapy. The rates of recurrent VTE and major bleeding were similar between the treatment arms, and overall bleeding was less with dabigatran. Dabigatran was approved in the United States in October 2010 for stroke prevention in atrial fibrillation but has yet to be approved for the treatment of VTE pending further study (clinicaltrials.gov Identifier: NCT00680186).
A study of oral rivaroxaban (Xarelto) for symptomatic VTE (the EINSTEIN-DVT trial) 52 randomized 3,449 patients with acute deep vein thrombosis to rivaroxaban or enoxaparin (Lovenox) overlapped with warfarin or another vitamin K antagonist in the usual manner. No difference was noted between the treatments in the rate of recurrence of VTE or of major bleeding. Of note, patients randomized to rivaroxaban received 15 mg twice a day for the first 3 weeks of treatment and then 20 mg per day for the remainder of their therapy and did not require parenteral anticoagulant overlap.
The long-awaited promise of easier-to-use oral anticoagulants for the treatment of VTE is drawing near and has the potential to revolutionize the treatment of this common disorder. In the meantime, close monitoring of warfarin and careful patient education regarding its use are essential. And even with the development of new drugs in the future, it is still imperative that patients with acute VTE receive the correct length of anticoagulation treatment, are prescribed stockings to prevent postthrombotic syndrome, and are updated on routine cancer screening.
