Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Post-thrombotic (postphlebitic) syndrome

INTRODUCTION

Post-thrombotic syndrome is the development of symptoms and signs of chronic venous insufficiency following deep vein thrombosis (DVT) and is an all too common, burdensome, and costly complication [1]. The term “post-thrombotic” replaces the prior terminology "postphlebitic” syndrome [2]. A combination of reflux due to valvular incompetence, and venous hypertension due to thrombotic obstruction, is thought to contribute to post-thrombotic syndrome [3,4]. Symptoms and signs of chronic venous insufficiency may include pain, vein dilation, edema, skin pigmentation, and venous ulcers.

Prevention of DVT through prophylaxis, timely recognition and treatment of DVT, and prevention of recurrent DVT will continue to have the greatest impact on reducing the overall burden of post-thrombotic syndrome [5]. The treatment of lower extremity DVT is discussed separately. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)".)

PATHOPHYSIOLOGY

Post-thrombotic syndrome develops as a consequence of long-standing venous hypertension [5]. A combination of reflux due to valvular incompetence, and venous hypertension due to thrombotic obstruction, is thought to contribute to post-thrombotic syndrome [3,4]. One study identified a high peak reflux velocity in the deep proximal veins as an independent predictor of post-thrombotic syndrome [6]. Increased venous pressures are transmitted to the capillary beds, promoting transudation of fluid and large molecules, resulting in tissue edema, subcutaneous fibrosis, and, finally, tissue hypoxia and ulceration [7-9]. (See "Pathophysiology of chronic venous disease".)

Acute DVT causes obstruction of venous outflow, which can be partial or complete. Increased levels of inflammatory cytokines or adhesion molecules, such as interleukin-6 and intercellular adhesion molecule-1 have also been linked with the development of post-thrombotic syndrome, suggesting that inflammation may play a role in the pathophysiology of post-thrombotic syndrome [10-12]. The inflammatory response to acute thrombosis and the process of recanalization directly damages venous valves.

Reflux occurs early, progressively increasing from 17 percent of patients at one week to 69 percent of patients at one year following the diagnosis of DVT [13]. The degree of initial vein occlusion correlates with the likelihood of developing reflux [13]. Reflux in the more proximal lower extremity veins may be particularly important to the development of post-thrombotic syndrome. However, popliteal valve incompetence has also been found to increase the risk of post-thrombotic syndrome, particularly when combined with residual vein thrombosis [14,15]. (See 'Risk factors' below.)

                    

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2014. | This topic last updated: Jul 15, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Kahn SR, Partsch H, Vedantham S, et al. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 7:879.
  2. Porter JM, Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg 1995; 21:635.
  3. Franzeck UK, Schalch I, Jäger KA, et al. Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zürich study). Circulation 1996; 93:74.
  4. Bergan JJ, Schmid-Schönbein GW, Smith PD, et al. Chronic venous disease. N Engl J Med 2006; 355:488.
  5. Prandoni P, Kahn SR. Post-thrombotic syndrome: prevalence, prognostication and need for progress. Br J Haematol 2009; 145:286.
  6. Yamaki T, Nozaki M, Sakurai H, et al. High peak reflux velocity in the proximal deep veins is a strong predictor of advanced post-thrombotic sequelae. J Thromb Haemost 2007; 5:305.
  7. Nicolaides AN, Hussein MK, Szendro G, et al. The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 1993; 17:414.
  8. Araki CT, Back TL, Padberg FT, et al. The significance of calf muscle pump function in venous ulceration. J Vasc Surg 1994; 20:872.
  9. Welkie JF, Comerota AJ, Katz ML, et al. Hemodynamic deterioration in chronic venous disease. J Vasc Surg 1992; 16:733.
  10. Roumen-Klappe EM, Janssen MC, Van Rossum J, et al. Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study. J Thromb Haemost 2009; 7:582.
  11. Shbaklo H, Holcroft CA, Kahn SR. Levels of inflammatory markers and the development of the post-thrombotic syndrome. Thromb Haemost 2009; 101:505.
  12. Kahn SR, Shbaklo H, Shapiro S, et al. Effectiveness of compression stockings to prevent the post-thrombotic syndrome (the SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial. BMC Cardiovasc Disord 2007; 7:21.
  13. Markel A, Manzo RA, Bergelin RO, Strandness DE Jr. Valvular reflux after deep vein thrombosis: incidence and time of occurrence. J Vasc Surg 1992; 15:377.
  14. Prandoni P, Frulla M, Sartor D, et al. Vein abnormalities and the post-thrombotic syndrome. J Thromb Haemost 2005; 3:401.
  15. Roumen-Klappe EM, den Heijer M, Janssen MC, et al. The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study. Thromb Haemost 2005; 94:825.
  16. Meissner MH, Zierler BK, Bergelin RO, et al. Coagulation, fibrinolysis, and recanalization after acute deep venous thrombosis. J Vasc Surg 2002; 35:278.
  17. Killewich LA, Macko RF, Cox K, et al. Regression of proximal deep venous thrombosis is associated with fibrinolytic enhancement. J Vasc Surg 1997; 26:861.
  18. Singh H, Masuda EM. Comparing short-term outcomes of femoral-popliteal and iliofemoral deep venous thrombosis: early lysis and development of reflux. Ann Vasc Surg 2005; 19:74.
  19. O'shaughnessy AM, Fitzgerald DE. The patterns and distribution of residual abnormalities between the individual proximal venous segments after an acute deep vein thrombosis. J Vasc Surg 2001; 33:379.
  20. Meissner MH, Manzo RA, Bergelin RO, et al. Deep venous insufficiency: the relationship between lysis and subsequent reflux. J Vasc Surg 1993; 18:596.
  21. van Ramshorst B, van Bemmelen PS, Hoeneveld H, et al. Thrombus regression in deep venous thrombosis. Quantification of spontaneous thrombolysis with duplex scanning. Circulation 1992; 86:414.
  22. Meissner MH, Caps MT, Zierler BK, et al. Determinants of chronic venous disease after acute deep venous thrombosis. J Vasc Surg 1998; 28:826.
  23. Markel A, Meissner M, Manzo RA, et al. Deep venous thrombosis: rate of spontaneous lysis and thrombus extension. Int Angiol 2003; 22:376.
  24. Tick LW, Doggen CJ, Rosendaal FR, et al. Predictors of the post-thrombotic syndrome with non-invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis. J Thromb Haemost 2010; 8:2685.
  25. Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis 2009; 28:465.
  26. Baldwin MJ, Moore HM, Rudarakanchana N, et al. Post-thrombotic syndrome: a clinical review. J Thromb Haemost 2013; 11:795.
  27. Kahn SR, Kearon C, Julian JA, et al. Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis. J Thromb Haemost 2005; 3:718.
  28. Partsch H, Kaulich M, Mayer W. Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. Int Angiol 2004; 23:206.
  29. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125:1.
  30. Tick LW, Kramer MH, Rosendaal FR, et al. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost 2008; 6:2075.
  31. Kahn SR, Shrier I, Julian JA, et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149:698.
  32. 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.
  33. 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; 101:23.
  34. Asbeutah AM, Riha AZ, Cameron JD, McGrath BP. Five-year outcome study of deep vein thrombosis in the lower limbs. J Vasc Surg 2004; 40:1184.
  35. van Rij AM, Hill G, Krysa J, et al. Prospective study of natural history of deep vein thrombosis: early predictors of poor late outcomes. Ann Vasc Surg 2013; 27:924.
  36. Kahn SR. The post-thrombotic syndrome: progress and pitfalls. Br J Haematol 2006; 134:357.
  37. van Dongen CJ, Prandoni P, Frulla M, et al. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005; 3:939.
  38. Prandoni P, Lensing AW, Prins MH, et al. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med 2004; 141:249.
  39. Ageno W, Piantanida E, Dentali F, et al. Body mass index is associated with the development of the post-thrombotic syndrome. Thromb Haemost 2003; 89:305.
  40. Galanaud JP, Holcroft CA, Rodger MA, et al. Comparison of the Villalta post-thrombotic syndrome score in the ipsilateral vs. contralateral leg after a first unprovoked deep vein thrombosis. J Thromb Haemost 2012; 10:1036.
  41. Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002; 162:1144.
  42. Spiezia L, Campello E, Giolo E, et al. Thrombophilia and the risk of post-thrombotic syndrome: retrospective cohort observation. J Thromb Haemost 2010; 8:211.
  43. Labropoulos N, Jen J, Jen H, et al. Recurrent deep vein thrombosis: long-term incidence and natural history. Ann Surg 2010; 251:749.
  44. Labropoulos N, Gasparis AP, Tassiopoulos AK. Prospective evaluation of the clinical deterioration in post-thrombotic limbs. J Vasc Surg 2009; 50:826.
  45. Labropoulos N, Gasparis AP, Pefanis D, et al. Secondary chronic venous disease progresses faster than primary. J Vasc Surg 2009; 49:704.
  46. Ginsberg JS, Hirsh J, Julian J, et al. Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med 2001; 161:2105.
  47. Wille-Jørgensen P, Jorgensen LN, Crawford M. Asymptomatic postoperative deep vein thrombosis and the development of postthrombotic syndrome. A systematic review and meta-analysis. Thromb Haemost 2005; 93:236.
  48. Strandness DE Jr, Langlois Y, Cramer M, et al. Long-term sequelae of acute venous thrombosis. JAMA 1983; 250:1289.
  49. 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; 21:307.
  50. van Ramshorst B, van Bemmelen PS, Hoeneveld H, Eikelboom BC. The development of valvular incompetence after deep vein thrombosis: a follow-up study with duplex scanning. J Vasc Surg 1994; 19:1059.
  51. McEnroe CS, O'Donnell TF Jr, Mackey WC. Correlation of clinical findings with venous hemodynamics in 386 patients with chronic venous insufficiency. Am J Surg 1988; 156:148.
  52. Sethia KK, Darke SG. Long saphenous incompetence as a cause of venous ulceration. Br J Surg 1984; 71:754.
  53. Labropoulos N, Leon M, Geroulakos G, et al. Venous hemodynamic abnormalities in patients with leg ulceration. Am J Surg 1995; 169:572.
  54. Philbrick JT, Becker DM. Calf deep venous thrombosis. A wolf in sheep's clothing? Arch Intern Med 1988; 148:2131.
  55. McLafferty RB, Moneta GL, Passman MA, et al. Late clinical and hemodynamic sequelae of isolated calf vein thrombosis. J Vasc Surg 1998; 27:50.
  56. Chitsike RS, Rodger MA, Kovacs MJ, et al. Risk of post-thrombotic syndrome after subtherapeutic warfarin anticoagulation for a first unprovoked deep vein thrombosis: results from the REVERSE study. J Thromb Haemost 2012; 10:2039.
  57. Hull RD, Liang J, Townshend G. Long-term low-molecular-weight heparin and the post-thrombotic syndrome: a systematic review. Am J Med 2011; 124:756.
  58. González-Fajardo JA, Martin-Pedrosa M, Castrodeza J, et al. Effect of the anticoagulant therapy in the incidence of post-thrombotic syndrome and recurrent thromboembolism: Comparative study of enoxaparin versus coumarin. J Vasc Surg 2008; 48:953.
  59. Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366:1959.
  60. Enden T, Haig Y, Kløw NE, et al. 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; 379:31.
  61. Henke PK, Comerota AJ. An update on etiology, prevention, and therapy of postthrombotic syndrome. J Vasc Surg 2011; 53:500.
  62. Verhovsek M, Douketis JD, Yi Q, et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 2008; 149:481.
  63. Cosmi B, Legnani C, Tosetto A, et al. Sex, age and normal post-anticoagulation D-dimer as risk factors for recurrence after idiopathic venous thromboembolism in the Prolong study extension. J Thromb Haemost 2010; 8:1933.
  64. Latella J, Desmarais S, Miron MJ, et al. Relation between D-dimer level, venous valvular reflux and the development of post-thrombotic syndrome after deep vein thrombosis. J Thromb Haemost 2010; 8:2169.
  65. Villalta S, Prandoni P, Cogo A, et al. The utility of non-invasive tests for detection of previous proximal-vein thrombosis. Thromb Haemost 1995; 73:592.
  66. Kahn SR. How I treat postthrombotic syndrome. Blood 2009; 114:4624.
  67. Cohen JM, Akl EA, Kahn SR. Pharmacologic and compression therapies for postthrombotic syndrome: a systematic review of randomized controlled trials. Chest 2012; 141:308.
  68. Kahn SR, Shrier I, Shapiro S, et al. Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial. CMAJ 2011; 183:37.
  69. Lattimer CR, Azzam M, Kalodiki E, et al. Compression stockings significantly improve hemodynamic performance in post-thrombotic syndrome irrespective of class or length. J Vasc Surg 2013; 58:158.
  70. Holmes CE, Bambace NM, Lewis P, et al. Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome. Vasc Med 2014; 19:42.
  71. Ginsberg JS, Magier D, Mackinnon B, et al. Intermittent compression units for severe post-phlebitic syndrome: a randomized crossover study. CMAJ 1999; 160:1303.
  72. Levi M. A long-awaited small step forward in the management of the post-thrombotic syndrome. Thromb Haemost 2008; 99:463.
  73. Gloviczki P, Bergan JJ, Rhodes JM, et al. Mid-term results of endoscopic perforator vein interruption for chronic venous insufficiency: lessons learned from the North American subfascial endoscopic perforator surgery registry. The North American Study Group. J Vasc Surg 1999; 29:489.
  74. Perrin M, Hiltbrand B, Bayon JM. Results of valvuloplasty in patients presenting deep venous insufficiency and recurring ulceration. Ann Vasc Surg 1999; 13:524.
  75. Meissner MH, Gloviczki P, Comerota AJ, et al. 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.
  76. Casey ET, Murad MH, Zumaeta-Garcia M, et al. Treatment of acute iliofemoral deep vein thrombosis. J Vasc Surg 2012; 55:1463.
  77. Nayak L, Hildebolt CF, Vedantham S. Postthrombotic syndrome: feasibility of a strategy of imaging-guided endovascular intervention. J Vasc Interv Radiol 2012; 23:1165.
  78. Khanna AK, Singh S. Postthrombotic syndrome: surgical possibilities. Thrombosis 2012; 2012:520604.
  79. Hartung O, Otero A, Boufi M, et al. Mid-term results of endovascular treatment for symptomatic chronic nonmalignant iliocaval venous occlusive disease. J Vasc Surg 2005; 42:1138.
  80. Raju S, Fredericks RK, Neglèn PN, Bass JD. Durability of venous valve reconstruction techniques for "primary" and postthrombotic reflux. J Vasc Surg 1996; 23:357.
  81. Raju S, Neglén P, Doolittle J, Meydrech EF. Axillary vein transfer in trabeculated postthrombotic veins. J Vasc Surg 1999; 29:1050.
  82. Bry JD, Muto PA, O'Donnell TF, Isaacson LA. The clinical and hemodynamic results after axillary-to-popliteal vein valve transplantation. J Vasc Surg 1995; 21:110.
  83. Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Intern Med 2004; 164:17.
  84. Bergqvist D, Jendteg S, Johansen L, et al. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med 1997; 126:454.
  85. Kahn SR, Shbaklo H, Lamping DL, et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost 2008; 6:1105.
  86. Ashrani AA, Silverstein MD, Rooke TW, et al. Impact of venous thromboembolism, venous stasis syndrome, venous outflow obstruction and venous valvular incompetence on quality of life and activities of daily living: a nested case-control study. Vasc Med 2010; 15:387.