Venous thromboembolism (VTE) is associated with significant mortality and morbidity, including post-thrombotic syndrome (PTS). VTE is considered as a chronic disease with pulmonary embolism (PE) and deep vein thrombosis (DVT) being different manifestations of the same disease process.
Currently, patients with a first episode of unprovoked proximal DVT or PE, with no apparent other risk factors for recurrent VTE, are given a course of oral anticoagulation (warfarin in the UK) treatment which is then discontinued. The optimum duration of warfarin therapy depends on the individual patient and has not been defined . Concern in terms of duration of treatment is due to the risk of bleeding from prolonged warfarin treatment. Several studies have investigated the optimal duration of anticoagulant therapy with the British Committee for Standards in Haematology (BCSH, 1998) recommending between six weeks and six months, depending upon the aetiology [2, 3].
A substantial proportion of patients – up to 17% [4–7] go on to have a recurrent episode of VTE which can be a potentially life-threatening condition . If recurrence occurs, the patient is normally managed thereafter with long-term warfarin, provided there are no contraindications. Although optimal duration of anticoagulation treatment for patients with a first idiopathic VTE remains uncertain, randomised trials have suggested that patients should be treated for a minimum of three months  but beyond that the duration of anticoagulation has little effect on the rate of recurrence3. There is an annual recurrence rate following a first VTE of approximately 10% per annum following treatment cessation, irrespective of the duration of warfarin therapy . This suggests that some patients with a first unprovoked VTE should continue warfarin in the long-term however we are currently unable to identify this population. Studies of extended treatment with low dose warfarin have confirmed that maximal benefit is conferred at standard therapeutic targets rather than fixed low dose regimes [11, 12].
It would be very useful to have an accurate predictor of recurrence of VTE to decide which patients with a first episode of unprovoked proximal DVT or PE would be most likely to benefit from long term oral anticoagulation, and also which patients should only receive short term therapy.
D-dimer is a fibrin degradation product, present in the blood after a blood clot is degraded by fibrinolysis and levels of D-dimer can be tested using laboratory and point-of-care (POC) testing devices. The primary clinical use of D-dimer testing has been in conjunction with probability scores to determine whether further investigation is required for the diagnosis of VTE. More recently interest has been shown in studies which have investigated whether D-dimer can be utilised as a guide for determining who is at risk of recurrent VTE following treatment of the initial acute episode [13, 14].
Previous small studies outside the UK have suggested that D-dimer levels could act as a useful predictor of recurrent thromboembolism in patients whose warfarin is discontinued [14–16]. There are limited data on utility of the D-dimer as a predictor in patients still on therapy, but Rodgers et al. have shown that D-dimer can be used to predict recurrence in low risk female patients . In addition to D-dimer levels a recent meta-analysis has suggested that age and gender may be effective in predicting recurrent VTE . This study concluded that men are at greater risk of developing a recurrent VTE after a first unprovoked episode and that age could be used as predictor in women. Therefore D-dimer levels could be a potentially useful clinical tool to decide which patients, with a first episode of unprovoked proximal DVT or PE, would most likely benefit from long-term warfarin therapy.
The conclusions of 2 systematic reviews of D-dimer testing after stopping treatment for VTE, (7 studies with a total of 1888 patients) were: “additional research is needed to establish the optimal interval between stopping anticoagulation and performing D-dimer testing, to identify the optimum cut-off that predicts recurrence and to develop a clinical prediction rule for recurrent DVT.” , and “strategies which incorporate a number of high performing baseline and post-baseline predictors could be more effective in predicting recurrent VTE and should be tested. If oral anticoagulation is continued, there is no evidence on the duration of this extended therapy .”
The only UK data included in these reviews were from a prospective cohort study of 272 patients with a first episode of venous thrombosis that was unprovoked or provoked by a non-surgical trigger. They undertook D-dimer testing 1 month after cessation of warfarin therapy and found a non-significant difference in recurrence (5.5/100 patients years in D-dimer + ve vs. 4.1/100 patient years in D-dimer –ve) .
PTS is a frequent and costly complication of DVT which can lead to chronic venous insufficiency and ulceration. PTS has a cumulative incidence after 2 years of around 25% and it has been postulated that prolonged treatment with oral anticoagulants could prevent the development of PTS . The only data available from a randomised trial suggested no association between long-term low dose warfarin treatment and development of PTS . The prevalence of PTS in this study was 37% after 2.2 years, with severe PTS in 4%. A recent study demonstrated an association between D-dimer level and the development of PTS , this is something that will be investigated during the course of this study.