ArticlesIncidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study
Introduction
After a first episode of venous thromboembolism (VTE), patients are usually treated with oral anticoagulation for between 6 weeks and 6 months.1 When treatment is stopped, the frequency of recurrence is 12–18% after 2 years.2, 3 The risk of recurrence is highest soon after the acute episode and it declines with time. Continued treatment with oral anticoagulant therapy will prevent most episodes of recurrence but there is a substantial risk of major bleeding associated with prolonged treatment.4, 5 In theory, anticoagulant treatment should be continued until the risk outweighs the benefit. However, the optimum duration of treatment is uncertain because the risk of bleeding associated with anticoagulation and the risk of recurrent VTE after stopping treatment are not easily predicted on an individual basis. Acquired risk factors are often identified in patients presenting with VTE, and heritable thrombophilic defects are identified in at least a third of patients with acute VTE.6 In this prospective cohort study, we aimed to determine the risk of recurrence in relation to clinical risk factors and standard laboratory testing for thrombophilic defects after a first episode of VTE.
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Patients
Since August, 1997, all patients referred for oral anticoagulant therapy at Addenbrooke's Hospital, Cambridge, UK, after a first episode of objectively confirmed VTE have been registered on a clinical outcome audit database. The database was registered with the hospital Clinical Audit and Effectiveness Unit. Thrombophilia testing was offered to all patients and 85% gave informed consent to have this test.
We excluded patients with antiphospholipid activity and those with malignant disease from
Procedures
Deep vein thrombosis was diagnosed by compression ultrasonography or contrast venography. Pulmonary embolus was diagnosed by ventilation-perfusion lung scanning, CT, or pulmonary angiography. Patients were treated with tinzaparin, European grade 1 or 2 compression stockings, and warfarin. All patients had a target International Normalised Ratio (INR) of 2·5.1
After treatment was completed, patients were counselled and offered thrombophilia testing. We told patients that the test results might
Results
We included 781 patients who registered at Addenbrooke's Hospital, Cambridge, between August, 1997, and January, 2002. 211 patients were excluded from further analysis either because of malignant disease at registration or follow-up (118), antiphospholipid syndrome (47), cerebral vein thrombosis (six), continued anticoagulant therapy (22), death (14), or proven recurrent symptomatic VTE before completing anticoagulant therapy (four). Thus, there were 570 patients in the final analyses— 86 in
Discussion
We have shown three important findings that could have implications for clinical practice. First, patients with postoperative VTE have a very low risk of recurrence and a low incidence of thrombophilic defects. Second, patients with unprecipitated VTE have a 20% cumulative recurrence rate at 2 years; however, despite 27% of patients having heritable thrombophilic defects, testing does not allow prediction of a high risk of recurrence. Third, patients with non-surgical triggers for a first VTE
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