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Predicting recurrence after a first unprovoked venous thromboembolism: Retrospective validation of the DAMOVES score

Published:April 06, 2017DOI:https://doi.org/10.1016/j.ejim.2017.03.022
      Unprovoked venous thromboembolism (VTE) is associated with a 5 to 27% annual risk of recurrence after discontinuation of anticoagulation (AC) [
      • Kearon C.
      • Gent M.
      • Hirsh J.
      • et al.
      A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.
      ,
      • Agnelli G.
      • Prandoni P.
      • Santamaria M.G.
      • Warfarin Optimal Duration Italian Trial Investigators
      • et al.
      Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.
      ,
      • Prandoni P.
      • Noventa F.
      • Ghirarduzzi A.
      • et al.
      The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients.
      ,
      • Rodger M.A.
      • Kahn S.R.
      • Wells P.S.
      • et al.
      Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.
      ], and indefinite AC is recommended if the bleeding risk is low to moderate [
      • Kearon C.
      • Akl E.A.
      • Ornelas J.
      • et al.
      Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.
      ]. However, in one-third of patients with unprovoked VTE, the risk of recurrence is so low (<3% per year) that anticoagulant therapy >3–6 months may not be necessary [
      • Rodger M.A.
      • Kahn S.R.
      • Wells P.S.
      • et al.
      Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.
      ,
      • Eichinger S.
      • Minar E.
      • Bialonczyk C.
      • et al.
      D-dimer levels and risk of recurrent venous thromboembolism.
      ]. Several prediction rules were derived to identify patients with unprovoked VTE who have a low recurrence risk [
      • Rodger M.A.
      • Kahn S.R.
      • Wells P.S.
      • et al.
      Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.
      ,
      • Tosetto A.
      • Iorio A.
      • Marcucci M.
      • et al.
      Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH).
      ,
      • Eichinger S.
      • Heinze G.
      • Jandeck L.M.
      • et al.
      Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model.
      ]. In 2016 in this journal, we published our results of the original DAMOVES score, which was derived in 398 patients with a first unprovoked VTE. Based on 7 parameters: age, sex, body mass index (BMI), D-dimer level during AC, factor VIII coagulant activity, genetic thrombophilia and varicose veins, we developed a nomogram for prediction of recurrence in an individual patient with unprovoked VTE [
      • Franco Moreno A.I.
      • García Navarro M.J.
      • Ortiz Sánchez J.
      • et al.
      A risk score for prediction of recurrence in patients with unprovoked venous thromboembolism (DAMOVES).
      ]. We aimed to validate this nomogram in patients with unprovoked VTE. A retrospective review was performed on a cohort of patients with unprovoked symptomatic deep vein thrombosis or pulmonary embolism from department of Internal Medicine of Torrejón University Hospital in Madrid, Spain, between August 2012 and October 2015. For the sake of this analysis, only patients with unprovoked VTE and who had completed at least 3 months AC were included. We determined the proportion of patients classified as low- vs higher-risk of VTE recurrence according to DAMOVES score (for this purpose, based on a consensus that an annual VTE recurrence rate below 5% was an acceptable risk; according to the nomogram, a score <11.5 points was considered a low recurrence risk). The Receiver Operating Characteristic (AUC) reflects the ability of the model to discriminate between patients with low- vs higher-risk of VTE recurrence. Stata 14.0 was used for the statistical analyses. In all statistical analyses, a P-value <0.05 was considered significant. A total of 121 patients with unprovoked VTE were included for the analysis. The median follow-up was 18 months after discontinuation the AC therapy. The proportion of VTE recurrence was 6,61% (8/121). In all patients, VTE recurred spontaneously. When applying, the cut-off point from the nomogram, 35 (28.92%) out of 121 subjects were categorized as having a low-risk of recurrent VTE, and 86 (71.07%) as having a high-risk. Table 1 shows the baseline characteristics of development and validation cohorts. Within these two categories, the observed prevalence of recurrent VTE was 2.85% (1 out of 35 subjects) in the low-risk category, and 20% (7 out of 86) in the high-risk category. The AUC of the nomogram in the external validation cohort was 0.83 ([95% confidence interval, 0.743–0.810], P-value <0.001). The model showed good calibration. The Hosmer-Lemeshow test showed consistent results (P-value = 0.125). In conclusions, DAMOVES score may be suitable for identifying patients with unprovoked VTE who are at low risk of VTE recurrence. Further studies should attempt to develop a prediction model or to update the DAMOVES nomogram.
      Table 1Comparison of baselines characteristics in the development and validation cohorts.
      Original (n = 398) External validation P-value
      All (n = 121) Low-risk patients (n = 35) Higher-risk patients (n = 86)
      n (%) or median (interquartile range)
      Age (years) 1.04 (1.01; 1.07) 72.0 (69.0; 79.8) 69.0 (62.0; 77.0) 78.0 (69.0; 81.0) 0.04
      Male sex 2.89 (1.21; 6.90) 81.0 (66.94) 12.0 (34.28) 69.0 (80.23) <0.01
      Obesity (BMI ≥30 kg/m2) 3.92 (1.75; 8.75) 78.0 (64.46) 8.0 (22.85) 70.0 (81.39) <0.01
      Elevated D-dimer levels during AC 13.66 (4.74; 39.37) 69.0 (57.02) 5.0 (14.28) 64.0 (74.41) <0.01
      Factor VIII coagulant activity 1.01 (1.00; 1.02) 128.0 (96; 181) 135.0 (96; 151) 171.0 (124; 181) <0.01
      Genetic thrombophilia
      Genetic thrombophilia: heterozygous of factor V Leiden and/or Prothrombin G20210A mutation.
      13.86 (5.87; 32.75) 66.0 (54.54) 13.0 (37.14) 53.0 (61.62) <0.01
      Varicose veins 4.14 (1.81; 9.43) 40.0 (33.05) 11.0 (31.42) 29.0 (33.72) 0.20
      a Genetic thrombophilia: heterozygous of factor V Leiden and/or Prothrombin G20210A mutation.

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