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Review

Post-thrombotic syndrome

A position paper from European Society of Vascular Medicine

Published Online:https://doi.org/10.1024/0301-1526/a000946

Summary: Post-thrombotic syndrome (PTS) is a chronic venous insufficiency manifestation following an episode of deep-vein thrombosis (DVT). It is an important and frequent long-term adverse event of proximal DVT affecting 20–50% of patients. This position paper integrates data guiding clinicians in deciding PTS diagnosis, treatment and follow-up.

References

  • 1 Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg NA, et al. American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014;130(18):1636–61. First citation in articleCrossref MedlineGoogle Scholar

  • 2 Galanaud JP, Monreal M, Kahn SR, Epidemiology of post-thrombotic syndrome. Thromb Res. 2018;164:100–9. First citation in articleCrossref MedlineGoogle Scholar

  • 3 Ten Cate AJ, Prevention and treatment of post-thrombotic syndrome. Res Pract Thromb Haemost. 2018;2:209–19. First citation in articleCrossref MedlineGoogle Scholar

  • 4 Prandoni P, Ageno W, Ciammaichella M, Mumoli N, Zanatta N, Imberti D, et al. For the DOAC-PTS Investigators. The risk of post-thrombotic syndrome in patients with proximal deep vein thrombosis treated with the direct oral anticoagulants. Intern Emerg Med. 2019. https://doi.org/10.1007/s11739-019-02215-z First citation in articleGoogle Scholar

  • 5 Kahn SR, M’Lan CE, Lamping DL, Kurz X, Bérard A, Abenhaim L. The influence of venous thromboembolism on quality of life and severity of chronic venous disease. J Thromb Haemost. 2004;2:2146–51. First citation in articleCrossref MedlineGoogle Scholar

  • 6 Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis. 2009;28(4):465–76. First citation in articleCrossref MedlineGoogle Scholar

  • 7 Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Pathol. 1974;27(7):517–28. First citation in articleCrossref MedlineGoogle Scholar

  • 8 Brooks EG, Trotman W, Wadsworth MP, Taatjes DJ, Evans MF, Ittleman FP, et al. Valves of the deep venous system: An overlooked risk factor. Blood. 2009;114(6):1276–9. First citation in articleCrossref MedlineGoogle Scholar

  • 9 Welsh JD, Hoofnagle MH, Bamezai S, Oxendine M, Lim L, Hall JD, et al. Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis. J Clin Invest. 2019;129(12):5489–500. First citation in articleCrossref MedlineGoogle Scholar

  • 10 Mukhopadhyay S, Johnson TA, Duru N, Buzza MS, Pawar NR, et al. Fibrinolysis and inflammation in venous thrombus resolution. Front Immunol. 2019;10:1–14. First citation in articleCrossref MedlineGoogle Scholar

  • 11 O’Shaushnessy AM, Fitzgerald DE. Natural history of proximal DVT assessed by duplex ultrasound. Int Angiol. 1997;16(1):45–9. First citation in articleMedlineGoogle Scholar

  • 12 Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg. 2002;24(3):209–14. First citation in articleCrossref MedlineGoogle Scholar

  • 13 Johnson BF, Manzo RA, Bergelin RO, Strandness DE Jr. Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up. J Vasc Surg. 1995;21(2):307–12. First citation in articleCrossref MedlineGoogle Scholar

  • 14 Rabinovich A, Kahn SR. How I treat the postthrombotic syndrome. Blood. 2018;131(20):2215–22. First citation in articleCrossref MedlineGoogle Scholar

  • 15 Nawasrah J, Zydek B, Lucks J, Renczes J, Haberichter B, Balaban U, et al. Incidence and severity of postthrombotic syndrome after iliofemoral thrombosis – results of the Iliaca-PTS – Registry. VASA. 2021;50(1):30–7. First citation in articleLinkGoogle Scholar

  • 16 Villalta S, Piccioli A, Lensing A, Prins M, Prandoni P. Assessment of validity and reproducibility of a clinical scale for the post- thrombotic syndrome [Abstract]. Haemostasis. 1994;24(158a). First citation in articleGoogle Scholar

  • 17 Ginsberg JS, Hirsh J, Julian J, Vander Laande Vries M, Magier D, MacKinnon B, et al. Prevention and treatment of post-phlebitic syndrome: results of a 3-part study. Arch Intern Med. 2001;161(17):2105–9. First citation in articleCrossref MedlineGoogle Scholar

  • 18 Wik HS, Enden TR, Ghanima W, Engeseth M, Kahn SR, Sandset PM. Diagnostic scales for the post-thrombotic syndrome. Thromb Res. 2018;164:110–5. First citation in articleCrossref MedlineGoogle Scholar

  • 19 Eklöf B, Rutherford RB, Bergan JJ, Carpentier PH, Gloviczki P, Kistner RL, et al. American Venous Forum International Ad Hoc Committee for Revision of the CEAP Classification. Revision of the CEAP classification for chronic venous disorders: Consensus statement. J Vasc Surg. 2004;40(6):1248–52. First citation in articleCrossref MedlineGoogle Scholar

  • 20 Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearson C. Definitionof post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardisation. J Thromb Haemost. 2009;7:879–83. First citation in articleCrossref MedlineGoogle Scholar

  • 21 Lattimer CR, Kalodiki E, Azzam M, Geroulakos G. Validation of the Villalta scale in assessing post-thrombotic syndrome using clinical, duplex, and hemodynamic comparators. J Vasc Surg Venous Lymphat Disord. 2014;2(1):8–14. First citation in articleCrossref MedlineGoogle Scholar

  • 22 Editor’s Choice – Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2015;49(6):678–737. First citation in articleCrossref MedlineGoogle Scholar

  • 23 Haenen JH, Van Langen H, Janssen MC, Wollersheim H, Van’t Hof MA, Skotnicki SH, et al. Venous duplex scanning of the leg: range, variability and reproducibility. Clin Sci. 1999;96:271–7. First citation in articleCrossrefGoogle Scholar

  • 24 Labropoulos N, Tiongson J, Pryor L, Tassiopoulos AK, Kang SS, Ashraf Mansour M, et al. Definition of venous reflux in lower-extremity veins. J Vasc Surg. 2003;38(4):793–8. First citation in articleCrossref MedlineGoogle Scholar

  • 25 Prandoni P, Lensing AWA, Prins MH, Bernardi E, Marchiori A, Bagatella P, et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med. 2002;137:985–90. First citation in articleCrossrefGoogle Scholar

  • 26 Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, et al. CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012;379(9810):31–8. First citation in articleCrossref MedlineGoogle Scholar

  • 27 Haig Y, Enden T, Grøtta O, Kløw NE, Slagsvold CE, Ghanima W, et al. CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016;3(2):e64–71. First citation in articleCrossref MedlineGoogle Scholar

  • 28 Vedantham S, Goldhaber SZ, Julian J, Kahn SR, Jaff MR, Cohen DJ, et al. ATTRACT Trial Investigators. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med. 2017;377:2240–52. First citation in articleCrossref MedlineGoogle Scholar

  • 29 Comerota AJ, Kearon C, Gu CS, Julian JA, Goldhaber SZ, Kahn SR, et al. ATTRACT Trial Investigators. Endovascular thrombus removal for acute iliofemoral deep vein thrombosis. Circulation. 2019;139(9):1162–73. First citation in articleCrossref MedlineGoogle Scholar

  • 30 Notten P, Ten Cate-Hoek AJ, Arnoldussen CWKP, Strijkers RHW, de Smet AAEA, Tick LW, et al. Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial. Lancet Haematol. 2020;7(1):e40–e49. First citation in articleCrossref MedlineGoogle Scholar

  • 31 Lichtenberg MKW, Stahlhoff S, Młyńczak K, Golicki D, Gagne P, Razavi MK, et al. Endovascular mechanical thrombectomy versus thrombolysis in patients with iliofemoral deep vein thrombosis – a systematic review and meta-analysis. VASA. 2021;50(1):59–67. First citation in articleLinkGoogle Scholar

  • 32 Brandjes DP, Buller HR, Heijboer H, Hulsman MV, de Rijk M, Jagt H. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349:759–62. First citation in articleCrossref MedlineGoogle Scholar

  • 33 Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E, et al.. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med. 2004;141:249–56. First citation in articleCrossref MedlineGoogle Scholar

  • 34 Prandoni P, Noventa F, Quintavalla R, Bova C, Cosmi B, Siragusa S, et al. Canano Investigators. Thigh-length versus below-knee compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial. Blood. 2012;119:1561–65. First citation in articleCrossref MedlineGoogle Scholar

  • 35 Kahn SR, Shapiro S, Wells PS, Rodger MA, Kovacs MJ, Anderson DR, et al. SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo controlled trial. Lancet. 2014;383:880–88. First citation in articleCrossref MedlineGoogle Scholar

  • 36 Mol GC, van de Ree MA, Klok FA, Tegelberg MJ, Sanders FB, Koppen S, et al. One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial. BMJ. 2016;353:i2691–99. First citation in articleCrossref MedlineGoogle Scholar

  • 37 Subbiah R, Aggarwal V, Zhao H, Kolluri R, Chatterjee S, Bashir R. Effect of compression stockings on post thrombotic syndrome in patients with deep vein thrombosis: a meta-analysis of randomised controlled trials. Lancet Haematol. 2016;3(6):e293–e300. First citation in articleCrossref MedlineGoogle Scholar

  • 38 Ten Cate-Hoek AJ, Amin EE, Bouman AC, Meijer K, Tick LW, Middeldorp S, et al. IDEAL DVT investigators. Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial. Lancet Haematol. 2018;5(1):e25–e33. First citation in articleCrossref MedlineGoogle Scholar

  • 39 Dronkers CEA, Mol GC, Maraziti G, van de Ree MA, Huisman MV, Becattini C, et al. Predicting post-thrombotic syndrome with ultrasonographic follow-up after deep vein thrombosis: a systematic review and meta-analysis. Thromb Haemost. 2018;118:1428–38. First citation in articleCrossref MedlineGoogle Scholar

  • 40 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;3:939–42. First citation in articleCrossref MedlineGoogle Scholar

  • 41 Prandoni P, Lensing AW, Prins MH, Pesavento R, Piccioli A, Sartori MT, et al. The impact of residual thrombosis on the long-term outcome of patients with deep venous thrombosis treated with conventional anticoagulation. Semin Thromb Hemost. 2015;41:133–40. First citation in articleCrossref MedlineGoogle Scholar

  • 42 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014;124:1968–75. First citation in articleCrossref MedlineGoogle Scholar

  • 43 Prandoni P, Ageno W, Mumoli N, Zanatta N, Imberti D, Visonà A, et al. Recanalization rate in patients with proximal vein thrombosis treated with the direct oral anticoagulants. Thromb Res. 2017;153:97–100. First citation in articleCrossref MedlineGoogle Scholar

  • 44 Li R, Yuan M, Cheng J, Yu S, Wei W, Fu W, et al. Risk of post-thrombotic syndrome after deep vein thrombosis treated with rivaroxaban versus vitamin-K antagonists: A systematic review and meta-analysis. Thromb Res. 2020;17(196):340–8. First citation in articleCrossrefGoogle Scholar

  • 45 Rabinovich A, Ducruet T, Kahn SR, SOX Trial investigators. Development of a clinical prediction model for the postthrombotic syndrome in a prospective cohort of patients with proximal deep vein thrombosis. J Thromb Haemost. 2018;16:262–70. First citation in articleCrossref MedlineGoogle Scholar

  • 46 Amin EE, van Kuijk SMJ, Joore MA, Prandoni P, Cate HT, Cate-Hoek AJT. Development and validation of a practical two-step prediction model and clinical risk score for post-thrombotic syndrome. Thromb Haemost. 2018;118:1242–49. First citation in articleCrossref MedlineGoogle Scholar

  • 47 Urbanek T, Labropoulos N. Can we predict and prevent the postthrombotic syndrome? VASA. 2021;50(1):11–21. First citation in articleLinkGoogle Scholar

  • 48 Mol GC, van de Ree MA, Klok FA, Tegelberg MJ, Sanders FB, Koppen S, et al. One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial. BMI. 2016;353:i2691. First citation in articleCrossref MedlineGoogle Scholar

  • 49 Klonizakis M, Tew G, Michaels J, Saxton J. Exercise training improves cutaneous microvascular endothelial function in post-surgical varicose vein patients. Microvasc Res. 2009;78:67–70. First citation in articleCrossref MedlineGoogle Scholar

  • 50 Klonizakis M, Tew G, Michaels J, Tew GA, Michaels JA, Saxton JM. Effects of upper limb exercise on lower limb cutaneous microvascular function in post-surgical varicose-vein patients. Eur J Appl Physiol. 2010;109:1221–4. First citation in articleCrossref MedlineGoogle Scholar

  • 51 Caldwell K, Prior SJ, Kampmann M, Zhao L, McEvoy S, Goldberg AP, et al. Upper body exercise increase lower extremity venous blood flow in deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2013;1(2):126–33. First citation in articleCrossref MedlineGoogle Scholar

  • 52 Ramos-González E, Moreno-Lorenzo C, Matarán-Peñarrocha GA, Guisado-Barrilao R, Aguilar-Ferrándiz ME, Castro-Sánchez AM. Comparative study on the effectiveness of myofascial release manual therapy and physical therapy for venous insufficiency in postmenopausal women. Complement Ther Med. 2012;20:291–8. First citation in articleCrossref MedlineGoogle Scholar

  • 53 Uhl JF, Gillot C. Anatomy of the veno-muscular pumps of the lower limb. Phlebology. 2015;30:180–93. First citation in articleCrossref MedlineGoogle Scholar

  • 54 Saggini R, Bellomo RG, Iodice P, Lessiani G. Venous insufficiency and foot dysmorphism: effectiveness of viscoelastic rehabilitation systems on veno-muscle system of the foot and of the calf. Int J Immunopathol Pharmacol. 2009;22(3 Suppl):1–8. First citation in articleCrossref MedlineGoogle Scholar

  • 55 Uhl JF, Chahim M, Allaert FA. Compression versus inner sole for venous patients with foot static disorders: a prospective trial comparing symptoms and quality of life. Phlebology. 2013;27:19–30. First citation in articleGoogle Scholar

  • 56 Partsch H, Blattler W. Compression and walking versus bed rest in the treatment of proximal deep venous thrombosis with low molecular weight heparin. J Vasc Surg. 2000;32(5):861–9. First citation in articleCrossref MedlineGoogle Scholar

  • 57 Tick LW, Middeldorp S, Mostard GJM, Ten Wolde M, van den Heiligenberg SM, van Wissen S, et al. Clinical and economic impact of compression in the acute phase of deep vein thrombosis. J Thromb Haemost. 2018;16:1555–63. First citation in articleCrossrefGoogle Scholar

  • 58 Amin EE, Bistervels IM, Meijer K, Tick LW, Middeldorp S, Mostard G, et al. Reduced incidence of vein occlusion and postthrombotic syndrome after immediate compression for deep vein thrombosis. Blood. 2018;132(21):2298–304. First citation in articleCrossref MedlineGoogle Scholar

  • 59 Holmes CE, Bambace NM, Lewis P, Callas PW, Cushman M. Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome. Vasc Med. 2014;19(1):42–8. First citation in articleCrossref MedlineGoogle Scholar

  • 60 Frank U, Nikol S, Belch J, Boc V, Brodmann M, Carpentier PH, et al.. ESVM Guideline on peripheral arterial disease. VASA. 2019;48(Suppl 102):1–79. First citation in articleAbstractGoogle Scholar

  • 61 Cohen JM, Akl EA, Kahn SR. Pharmacologic and compression therapies for post- thrombotic syndrome: a systematic review of randomized controlled trials. Chest. 2012;141(2):308–20. First citation in articleCrossref MedlineGoogle Scholar

  • 62 Razavi MK, Jaff MR, Miller LE. Safety and Effectiveness of Stent Placement for Iliofemoral Venous Outflow Obstruction: Systematic Review and Meta-Analysis. Circ Cardiovasc Interv. 2015;8(10):e002772. First citation in articleCrossref MedlineGoogle Scholar

  • 63 Garcia MJ, Sterling KM, Kahn SR, Comerota AJ, Jaff MR, Ouriel K, et al. ACCESS PTS Investigators. Ultrasound-accelerated thrombolysis and venoplasty for the treatment of the postthrombotic syndrome: Results of the ACCESS PTS study. J Am Heart Assoc. 2020;9(3):e013398. First citation in articleCrossref MedlineGoogle Scholar

  • 64 Neglen P, Berry MA, Raju S. Endovascular surgery in the treatment of chronic primary and post-thrombotic iliac vein obstruction. Eur J Vasc Endovasc Surg. 2000;20:560–7. First citation in articleCrossref MedlineGoogle Scholar

  • 65 Raju S, Darcey R, Neglen P. Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg. 2010;51:401–9. First citation in articleCrossref MedlineGoogle Scholar

  • 66 Seager MJ, Busuttil A, Dharmarajah B, Davies AH. A systematic review of endovenous stenting in chronic venous disease secondary to iliac vein obstruction. Eur J Vasc Endovasc Surg. 2016;51:100–20. First citation in articleCrossref MedlineGoogle Scholar

  • 67 Vedantham S, Kahn SR, Goldhaber SZ, Comerota AJ, Parpia S, Meleth S, et al. Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel. Vasc Med. 2016;21(4):400–7. First citation in articleCrossref MedlineGoogle Scholar

  • 68 Maleti O, Perrin M. Reconstructive surgery for deep vein reflux in the lower limbs: techniques, results and indication. Eur J Vasc Endovasc Surg. 2011;41:837–48. First citation in articleCrossref MedlineGoogle Scholar

  • 69 Meissner MH, Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, et al., Society for Vascular Surgery; American Venous Forum. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2012;55:1449–62. First citation in articleCrossref MedlineGoogle Scholar

  • 70 Quéré I, Elias A, Maufus M, Elias M, Sevestre MA, Galanaud JP, et al. Unresolved questions on venous thromboembolic disease. Consensus statement of the French Society for Vascular Medicine (SFMV). J Med Vasc. 2019;44(1):28–70. First citation in articleMedlineGoogle Scholar