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• W2016152002 abstract "The influence of thrombophilic mutations on the risk of recurrent venous thromboembolism (VTE) is complex, as there may be interactions with environmental factors such as use of oral contraceptives [1], smoking [2], obesity [2], age [2], and hyperhomocysteinemia [3]. In addition, the duration of follow-up since the index event of VTE also seems to be of importance. In the DURAC I study, we could not find a statistically significant difference in the risk of recurrence between non-carriers and carriers of factor V Leiden or prothrombin G20210A polymorphism after 48 months of follow-up [4]. After 10 years of follow-up, there was, however, a significant association between the presence of FV Leiden in heterozygous form (P = 0.028) or homozygous form (P = 0.030) and recurrence in multivariate analysis [5]. The increased effect over time can be interpreted as a result of a genetic factor that that exerts a small but constant threat, aggravated by one or several intercurrent environmental factors. Related to the duration of follow-up is the effect of duration of anticoagulation. Santamaria et al. found in a substudy on 195 patients from the WODIT trial that the increased risk of recurrent VTE (absolute difference 14%) in patients with thrombophilic abnormalities was accounted for by those only receiving 3 months of anticoagulation [6]. Likewise, in this issue of the Journal, Prandoni et al. demonstrate that in a cohort of 714 patients, the absolute increase in risk of recurrence of 11% is explained by the subset receiving only 3 months of secondary prophylaxis [7]. We have analyzed the data from the DURAC I study in a similar way. In our trial, patients received vitamin K antagonist for 6 weeks or 6 months after their first episode of VTE. Patients with known cancer or with deficiency of antithrombin, protein C or protein S were not included. For this analysis, we also excluded patients with cancer diagnosed during the first 6 months after the index event and patients with systemic lupus erythematosus. We did not test for lupus anticoagulant and we did not exclude those with cardiolipin antibodies, as many had low titers, the significance of which can be debated. The remaining 496 patients were distributed equally between the 6-week and 6-month treatment groups (Table 1). The proportion of patients with a recurrence over 10 years was 28% in both groups. In the 6-week group, there was no difference in the rate of recurrence between those with and those without any of the two polymorphisms. Somewhat surprisingly, in the 6-month group, the risk of recurrence was higher among those with than those without defects, 44% vs. 21% (chi-square with Yates’ correction; P < 0.001). This is in contradiction to the findings of Santamaria et al. [6] and Prandoni et al. [7]. The differences between our material and the Italian studies are ethnicity, shorter treatment in the short-duration group (6 weeks vs. 3 months) and longer follow-up (120 vs. 50–60 months), but the differences may be spurious, resulting from relatively small numbers. There are obvious limitations of an analysis that is performed retrospectively after 10 years of follow-up, due to losses from follow-up. It should be realized that only a small proportion of the recurrences are explained by the presence of a polymorphism in the FII or FV gene, and that other determinants, such as unprovoked thromboembolism and the pure fact that a thromboembolic event has occurred, play a greater role in the risk of recurrence. We think it is still too early to conclude that all patients with VTE should be investigated for these polymorphisms, so that those with defects can be treated for more than 3 months. The authors state that they have no conflict of interest." @default.
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• W2016152002 date "2008-12-01" @default.
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• W2016152002 title "Thrombophilic polymorphism – a short‐term or long‐term risk for recurrence?" @default.
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• W2016152002 doi "https://doi.org/10.1111/j.1538-7836.2008.03208.x" @default.
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