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Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosisA patient-level meta-analysis
23 April 2013
Accepted after major revision: 12 September 2013
29 November 2017 (online)
Residual venous obstruction (RVO) could improve the stratification of the risk of recurrence after unprovoked deep vein thrombosis (DVT), but results from clinical studies and study-level meta-analyses are conflicting. It was the objective of this analysis to determine if RVO is a valid predictor of recurrent venous thromboembolism (VTE) in patients with a first unprovoked DVT who had received at least three months of anticoagulant therapy. Individual patient data were obtained from the datasets of original studies, after a systematic search of electronic databases (Medline, Embase, Cochrane Library), supplemented by manual reviewing of the reference lists and contacting content experts. A multivariate, shared-frailty Cox model was used to calculate hazard ratios (HRs) for recurrent VTE, including, as covariates: RVO; age; sex; anticoagulation duration before RVO assessment; and anticoagulation continuation after RVO assessment. A total of 2,527 patients from 10 prospective studies were included. RVO was found in 1,380 patients (55.1%) after a median of six months from a first unprovoked DVT. Recurrent VTE occurred in 399 patients (15.8%) during a median follow-up of 23.3 months. After multivariate Cox analysis, RVO was independently associated with recurrent VTE (HR = 1.32, 95% confidence interval [CI]: 1.06–1.65). The association was stronger if RVO was detected early, i.e. at three months after DVT (HR = 2.17; 95% CI: 1.11–4.25), but non-significant if detected later, i.e. >6 months (HR = 1.19; 95% CI: 0.87–1.61). In conclusion, after a first unprovoked DVT, RVO is a weak overall predictor of recurrent VTE. The association is stronger if RVO is detected at an earlier time (3 months) after thrombosis.
KeywordsResidual venous obstruction - patient-level meta-analysis - unprovoked deep vein thrombosis - recurrent venous thromboembolism
- 1 Prandoni P, Cogo A, Bernardi E. et al. A simple ultrasound approach for detection of recurrent proximal vein thrombosis. Circulation 1993; 88: 1730-1735.
- 2 Le Gal G, Kovacs MJ, Carrier M. et al. Validation of a diagnostic approach to exclude recurrent venous thromboembolism. J Thromb Haemost 2009; 7: 752-759.
- 3 Hamadah A, Alwasaidi T, LE Gal G. et al. Baseline imaging after therapy for unprovoked venous thromboembolism: a randomized controlled comparison of baseline imaging for diagnosis of suspected recurrence. J Thromb Haemost 2011; 9: 2406-2410.
- 4 Kearon C, Akl EA, Comerota AJ. et al. American College of Chest Physicians. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th edition: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141: e419S-494S.
- 5 Donadini MP, Ageno W. Which patients with unprovoked VTE should receive extended anticoagulation? the minority. J Thromb Thrombolysis 2011; 31: 301-305.
- 6 Kearon C. Extended anticoagulation for unprovoked venous thromboembol-ism: a majority of patients should be treated. J Thromb Thrombolysis 2011; 31: 295-300.
- 7 Douketis J, Tosetto A, Marcucci M. et al. Risk of recurrence after venous throm-boembolism in men and women: patient level meta-analysis. Br Med J 2011; 342: d813
- 8 Douketis J, Tosetto A, Marcucci M. et al. Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of d-dimer testing to assess recurrence risk after unprovoked venous thromboembolism. Ann Intern Med 2010; 153: 523-531.
- 9 Stain M, Schönauer V, Minar E. et al. The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease. J Thromb Haemost 2005; 3: 2671-2676.
- 10 Prandoni P, Noventa F, Ghirarduzzi A. et al. The risk of recurrent venous throm-boembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92: 199-205.
- 11 Meissner MH, Zierler BK, Bergelin RO. et al. Coagulation, fibrinolysis, and re-canalization after acute deep venous thrombosis. J Vasc Surg 2002; 35: 278-285.
- 12 Prandoni P, Prins MH, Lensing AW. et al. AESOPUS Investigators. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep vein thrombosis. Ann Intern Med 2009; 150: 577-585.
- 13 Cosmi B, Legnani C, Iorio A. et al. PROLONG Investigators (on behalf of FCSA, Italian Federation of Anticoagulation Clinics). Residual Venous Obstruction, alone and in Combination with D-Dimer, as a Risk Factor for Recurrence after Anticoagulation Withdrawal following a First Idiopathic Deep Vein Thrombosis in the Prolong Study. Eur J Vasc Endovasc Surg 2010; 39: 356-365.
- 14 Le Gal G, Carrier M, Kovacs MJ. et al. Residual vein obstruction as a predictor for recurrent thromboembolic events after a first unprovoked episode: data from the REVERSE cohort study. J Thromb Haemost 2011; 9: 1126-1132.
- 15 Siragusa S, Malato A, Saccullo G. et al. Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study. Am J Hematol 2011; 86: 914-917.
- 16 Carrier M, Rodger MA, Wells PS. et al. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2011; 9: 1119-1125.
- 17 Tan M, Mos IC, Klok FA. et al. Residual venous thrombosis as predictive factor for recurrent venous thromboembolim in patients with proximal deep vein thrombosis: a sytematic review. Br J Haematol 2011; 153: 168-178.
- 18 Iorio A, Kearon C, Filippucci E. et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170: 1710.
- 19 Heit JA, Mohr DN, Silverstein MD. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761-768.
- 20 Righini M, Paris S, Le Gal G. et al. Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost 2006; 95: 56-64.
- 21 Wells GA, Shea B, O’Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Accessed March 19, 2013.
- 22 Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011 Available from www.cochrane-handbook.org.
- 23 Heijboer H, Jongbloets LM, Buller HR. et al. Clinical utility of real-time compression ultrasonography for diagnostic management of patients with recurrent venous thrombosis. Acta Radiologica 1992; 33: 297-300.
- 24 Piovella F, Crippa L, Barone M. et al. Normalization rates of compression ultra-sonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with DT recurrence and new thrombosis. Haematologica 2002; 87: 515-522.
- 25 Prandoni P, Lensing AW, Prins MH. et al. Residual thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med 2002; 137: 955-960.
- 26 Ageno W, Steidl L, Piantanida E. et al. Predictors of residual venous obstruction after deep vein thrombosis of the lower limbs: a prospective cohort study. Thromb Res 2003; 108: 203-207.
- 27 Cosmi B, Legnani C, Cini M. et al. D-dimer levels in combination with residual vein obstruction and the risk of recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis. Thromb Haemost 2005; 94: 969-974.
- 28 Young L, Ockelford P, Milne D. et al. Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality. J Thromb Hae-most 2006; 4: 1919-1192.
- 29 Poli D, Antonucci E, Ciuti G. et al. Combination of D-dimer, F1+2 as residual vein obtruction as predictors of VTE recurrence in patients with first VTE episode after OAT withdrawal. J Thromb Haemost 2008; 6: 708-710.
- 30 Siragusa S, Malato A, Anastasio R. et al. Residual vein thrombosis to estabilish duration of anticoagulation after a first episode of deep vein thrombosis: the duration of anticoagulation based on compresssion ultrasonography (DACUS) study. Blood 2008; 112: 511-515.
- 31 Kearon C, Ginsberg JS, Kovacs MJ. et al. Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
- 32 Kim TM, Kim JS, Han SW. et al. Clinical predictors of recurrent venous throm-boembolism: a single institute experience in Korea. Thromb Res 2009; 123: 436-443.
- 33 Kearon C, Ginsberg JS, Anderson DR. et al. SOFAST Investigators. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. J Thromb Haemost 2004; 2: 743-749.
- 34 Cosmi B, Legnani C, Cini M. et al. The role of D-dimer and residual venous obstruction in recurrence of venous thromboembolism after anticoagulation withdrawal in cancer patients. Haematologica 2005; 90: 713-715.
- 35 Kearon C, Gent M, Hirsh J. et al. A comparison of three months of anticoagu-lation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340: 901-907.
- 36 Linkins LA, Stretton R, Probyn L. et al. Interobserver agreement on ultrasound measurements of residual vein diameter, thrombus echogenicity and Doppler venous flow in patients with previous venous thrombosis. Thromb Res 2006; 117: 241-247.
- 37 Tan M, Bornais C, Rodger M. Interobserver reliability of compression ultrasound for residual thrombosis after first unprovoked deep vein thrombosis. J Thromb Haemost 2012; 10: 1775-1782.
- 38 Rodger MA, Kahn SR, Wells PS. et al. Identifying unprovoked thromboembol-ism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179: 417-426.
- 39 Eichinger S, Heinze G, Jandeck LM. et al. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 2010; 121: 1630-1636.
- 40 Tosetto A, Iorio A, Marcucci M. et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 2012; 10: 1019-1025.
- 41 Hull RD, Marder VJ, Mah AF. et al. Quantitative assessment of thrombus burden predicts the outcome of treatment for venous thrombosis: a systematic review. Am J Med 2005; 118: 456-464.
- 42 Gómez-Outes A, Lecumberri R, Lafuente-Guijosa A. et al. Correlation between thrombus regression and recurrent venous thromboembolism. Examining ve-nographic and clinical effects of low-molecular-weight heparins: a meta-analy-sis J Thromb Haemost 2004; 2: 1581-1587.
- 43 Aziz F, Comerota AJ. Quantity of residual thrombus after successful catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with recurrence. Eur J Vasc Endovasc Surg 2012; 44: 210-213.
- 44 Bates SM, Jaeschke R, Stevens SM. et al. American College of Chest Physicians. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e351S-418S.