Elsevier

The Lancet

Volume 362, Issue 9383, 16 August 2003, Pages 523-526
The Lancet

Articles
Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study

https://doi.org/10.1016/S0140-6736(03)14111-6Get rights and content

Summary

Background

Stratification for risk of recurrence after a first episode of venous thromboembolism (VTE) would affect the duration of anticoagulant therapy. We aimed to determine the incidence of recurrence of VTE in relation to clinical risk factors and standard laboratory testing for heritable thrombophilic defects.

Methods

We established a database to prospectively follow-up a cohort of unselected patients who had had a first episode of objectively proven VTE. We excluded patients with malignant disease and antiphospholipid syndrome. All patients were offered testing for heritable thrombophilia.

Findings

At 2 years, the cumulative recurrence rate in 570 patients was 11%. Incidence was lowest after surgery-related VTE (0%) and highest after unprecipitated VTE (19·4%) (p<0·001). 85% of patients were tested for heritable thrombophilic defects. Recurrence rates were not related to presence or absence of laboratory evidence of heritable thrombophilia (hazard ratio 1·50 [95% CI 0·82–2·77]; p=0·187). In patients with a first event that was unprecipitated or was associated with a non-surgical trigger, recurrence rates did not differ in patients with or without thrombophilia (1·34 [0·73–2·46]; p=0·351).

Interpretation

In unselected patients who have had a first episode of VTE, testing for heritable thrombophilia does not allow prediction of recurrent VTE in the first 2 years after anticoagulant therapy is stopped. However, assessment of clinical risk factors associated with the first episode of VTE does predict risk of recurrence. Patients with postoperative VTE have a very low rate of recurrence.

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.

Section snippets

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

References (21)

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