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While poor quality of oral anticoagulant therapy has been reported to be consistently associated with a higher incidence of later post-thrombotic syndrome in patients with deep vein thrombosis (DVT) of the lower extremities [1,2], whether poor anticoagulation quality may predict the development of subsequent recurrent venous thromboembolism (VTE) is uncertain, as information coming from two recent studies is conflicting [3,4].

We followed for up to 5 years 200 consecutive patients with a first episode of acute proximal DVT who had been treated with unfractionated or low-molecular weight heparin followed by 3–6 months of oral anticoagulant therapy. Patients who had indication for long-term anticoagulation were excluded from our evaluation. The main demographic and clinical characteristics of the study patients are shown in Table 1. The median duration of follow-up was 4.9 years (interquartile range, 3.9–4.9). The time spent in the targeted therapeutic range (INR, 2.0–3.0) and beneath the lower limit of the therapeutic range was calculated using linear interpolation. Overall, approximately 60% of time was spent in the therapeutic range, and 33% was spent beneath this range. A total of 58 of the 200 patients (29.0%) spent more than 50% of their time in the lowest INR category. Following discontinuation of oral anticoagulant therapy, recurrent VTE as assessed by objective tests developed in 25 patients (12.5%). The median time to recurrence was 35 months (interquartile range, 15–50). Of these 25 patients, six belonged to the 58 (10.3%) who spent more than 50%, and 19 to the 142 (13.4%) who spent < 50% of their time in the lowest INR category. The multivariate model including age (> 65 vs. < 65 years), gender and body mass index showed the lack of association between percentage of time spent beneath an INR level of 2.0 (> 50% vs. ≤ 50%) and risk of recurrent VTE (odds ratio, 0.74; 95% CI, 0.28–1.98).

Table 1.   Patients’ characteristics (n = 200)
  1. SD indicates standard deviation.

Median age (range)66 (51–75)
Age > 65 years (%)104 (52)
Male gender (%)84 (42)
Mean percentage time in target range ± SD59 ± 31

Our findings are consistent with those from a wide observational cohort study recently performed in the Netherlands [3], but are apparently in contrast to those obtained by Palareti et al. [4] in their prospective cohort study. However, it should be specified that Palareti et al. included only patients with idiopathic DVT, confined their evaluation to the first 3 months, and defined poor quality of anticoagulation as producing an INR beneath 1.5. At least when adopting the criteria used for this investigation, low quality of anticoagulation does not seem to be associated with an increased risk of subsequent recurrent VTE. However, as the quality of oral anticoagulant treatment has the potential firstly to prevent VTE recurrences occurring during the period of treatment [5], and secondly to prevent the occurrence of late post-thrombotic sequelae [1,2], patients and their attending physicians should not be dissuaded from carefully monitoring the INR level and from achieving the best level of anticoagulation.

References

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  2. References
  • 1
    Van Dongen CJ, Prandoni P, Frulla M, Marchiori A, Prins MH, Hutten BA. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005; 3: 93942.
  • 2
    Ziegler S, Schillinger M, Maca TH, Minar E. Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20 years ago. Thromb Res 2001; 101: 2333.
  • 3
    Gadisseur APA, Christiansen SC, Van Der Meer FJM, Rosendaal FR. The quality of oral anticoagulant therapy and recurrent venous thrombotic events in the Leiden Thrombophilia Study. J Thromb Haemost 2007; 5: 9316.
  • 4
    Palareti G, Legnani C, Cosmi B, Guazzaloca G, Cini M, Mattarozzi S. Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence. J Thromb Haemost 2005; 3: 95561.
  • 5
    Hull R, Raskob GE, Hirsh J, Sackett DL. A cost-effectiveness analysis of alternative approaches for long-term treatment of proximal venous thrombosis. JAMA 1984; 252: 2359.