Postthrombotic Syndrome

ABSTRACT

Despite considerable progress in the diagnosis and treatment of deep vein thrombosis (DVT) of the lower extremities, one of every three patients will develop postthrombotic sequelae within 2 years; these sequelae are severe in ~20% of cases and produce considerable socioeconomic consequences. Among factors potentially related to the development of the postthrombotic syndrome (PTS) are older age, obesity, insufficient oral anticoagulant therapy, and recurrent ipsilateral thrombosis. Whether the extent and location of the initial thrombosis are associated with the development of PTS is controversial. Based on recent findings, the lack of vein recanalization within the first 6 months appears to be an important predictor of PTS, whereas the development of transpopliteal venous reflux is not. The diagnosis of PTS can be made on clinical grounds for patients with a history of DVT. The combination of a standardized clinical evaluation with the results of compression ultrasonography and Doppler ultrasound helps diagnose or exclude a previous proximal vein thrombosis. According to the results of recent clinical studies, the prompt administration of adequate compression elastic stockings in patients with symptomatic DVT has the potential to reduce the frequency of late PTS development by half. The management of this condition is demanding and often frustrating. However, when carefully supervised and instructed to wear proper elastic stockings, more than 50% of patients will either remain stable or improve during long-term follow-up. Clinical presentation helps predict the prognosis; the outcome of patients who refer with initially severe manifestations is more favorable than that of patients whose symptoms deteriorate progressively over time.

KEYWORDS

Deep vein thrombosis - postthrombotic syndrome - postphlebitic syndrome - diagnosis - management - elastic stockings

REFERENCES

• 1 Kahn S R, Ginsberg J S. Relationship between deep venous thrombosis and the postthrombotic syndrome.  Arch Intern Med. 2004;  164 17-26
• 2 Bergqvist D, Jendteg S, Johansen L, Persson U, Ödegaard K. 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;  126 454-457
• 3 Bauer G. Roentgenological and clinical study of the sequelae of thrombosis.  Acta Chir Scand. 1942;  86(suppl 74) 1-110
• 4 Gjores J E. The incidence of venous thrombosis and its sequelae in certain districts of Sweden.  Acta Chir Scand. 1956;  206(suppl 1) 1-88
• 5 O'Donnell T F, Browse N L, Burnand K G, Lea Thomas M. The socioeconomic effects of an ilio-femoral venous thrombosis.  J Surg Res. 1977;  22 483-488
• 6 Shull K C, Nicolaides A N, Fernandes J F et al.. Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration.  Arch Surg. 1979;  114 1304-1306
• 7 Strandness D E, Langlois Y, Cramer M, Randlett A, Thiele B L. Long-term sequelae of acute venous thrombosis.  JAMA. 1983;  250 1289-1292
• 8 Widmer L K, Zemp E, Widmer T et al.. Late results in deep vein thrombosis of the lower extremity.  Vasa. 1985;  14 264-268
• 9 Lindner D J, Edwards J M, Phinney E S, Taylor L M, Porter J M. Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis.  J Vasc Surg. 1986;  4 436-442
• 10 Heldal M, Seem E, Snadset P M, Abildgaard U. Deep vein thrombosis: a 7-year follow-up study.  J Intern Med. 1993;  234 71-75
• 11 Lagerstedt C, Olsson C G, Fagher B, Norgren L, Tengborn L. Recurrence and late sequelae after first-time deep vein thrombosis. Relationship to initial signs.  Phlebology. 1993;  8 62-67
• 12 Monreal M, Martorell A, Callejas J M et al.. Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study.  J Intern Med. 1993;  234 233-238
• 13 Eichlisberger R, Frauchiger B, Widmer M T, Widmer L K, Jager K. Late sequelae of deep venous thrombosis: a 13-year follow-up of 223 patients.  Vasa. 1994;  23 234-243
• 14 Beyth R J, Cohen A M, Landefeld C S. Long-term outcomes of deep-vein thrombosis.  Arch Intern Med. 1995;  155 1031-1037
• 15 Johnson B F, Manzo R A, Bergelin R O, Strandness D E. 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;  21 307-313
• 16 Saarinen J, Sisto T, Laurikka J, Salenius J P, Tarkka M. Late sequelae of acute deep venous thrombosis: evaluation five and ten years after.  Phlebology. 1995;  10 106-109
• 17 Franzeck U K, Schalch I, Jäger K A, Schneider E, Grimm J, Bollinger A. Prospective 12-year follow-up study of clinical and haemodynamic sequelae after deep vein thrombosis in low-risk patients (Zürich study).  Circulation. 1996;  93 74-79
• 18 Prandoni P, Lensing A WA, Cogo A et al.. The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med. 1996;  125 1-7
• 19 Brandjes D PM, Büller H R, Heijboer H, Huisman M V, de Rijk M, Jagt H. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.  Lancet. 1997;  349 759-762
• 20 Prandoni P, Villalta S, Bagatella P et al.. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients.  Haematologica. 1997;  82 423-428
• 21 Biguzzi E, Mozzi E, Alatri A, Taioli E, Moia M, Mannucci P M. The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors.  Thromb Haemost. 1998;  80 575-577
• 22 Masuda E M, Kessler D M, Kistner R L, Eklof B, Sato D T. The natural history of calf vein thrombosis: lysis of thrombi and development of reflux.  J Vasc Surg. 1998;  28 67-74
• 23 McLafferty R B, Moneta G L, Passmann M A, Brant B M, Taylor L M, Porter J M. Late clinical and hemodynamic sequelae of isolated calf vein thrombosis.  J Vasc Surg. 1998;  27 50-57
• 24 Haenen J H, Janssen M CH, van Langen H et al.. The postthrombotic syndrome in relation to venous hemodynamics, as measured by means of duplex scanning and strain-gauge plethysmography.  J Vasc Surg. 1999;  29 1071-1076
• 25 Holmström M, Åberg W, Lockner C, Paul C. Long term clinical follow-up in 256 patients with deep-vein thrombosis initially treated with either unfractionated heparin or dalteparin: a retrospective analysis.  Thromb Haemost. 1999;  82 1222-1226
• 26 Saarinen J, Kallio T, Lehto M, Hiltunen S, Sisto T. The occurrence of the post-thrombotic changes after an acute deep venous thrombosis. A prospective two-year follow-up study.  J Cardiovasc Surg (Torino). 2000;  41 441-446
• 27 Mohr D N, Silverstein M D, Heit J A, Petterson T M, O'Fallon M, Melton L J. The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study.  Mayo Clin Proc. 2000;  75 1249-1256
• 28 Ziegler S, Schillinger M, Maca T H, Minar E. Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20 years ago.  Thromb Res. 2001;  101 23-33
• 29 Prandoni P, Lensing A WA, Prins M H et al.. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome. A randomized, controlled trial.  Ann Intern Med. 2004;  141 249-256
• 30 Gabriel F, Labios M, Portoles O et al.. Incidence of post-thrombotic syndrome and its association with various risk factors in a cohort of Spanish patients after one year of follow-up following acute deep venous thrombosis.  Thromb Haemost. 2004;  92 328-336
• 31 Kahn S R, Kearon C, Julian J A et al.. Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis.  J Thromb Haemost. 2005;  3 718-723
• 32 Roumen-Klappe E M, den Heijer M, Janssen M CH, van der Vleuten C, Thien T, Wollersheim H. The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study.  Thromb Haemost. 2005;  94 825-830
• 33 Immelman E J, Jeffrey P C. The postphlebitic syndrome. Pathophysiology, prevention and management.  Clin Chest Med. 1984;  5 537-550
• 34 Raju S. Venous insufficiency of the lower limbs and stasis ulceration.  Ann Surg. 1983;  197 688-697
• 35 Scott T E, LaMorte W W, Gorin D R, Menzoian J O. Risk factors for chronic venous insufficiency: a dual case-control study.  J Vasc Surg. 1995;  22 622-628
• 36 Browse N L, Clemenson G, Lea Thomas M. Is the postphlebitic leg always postphlebitic? Relation between phlebographic appearances of deep-vein thrombosis and late sequelae.  BMJ. 1980;  281 1167-1170
• 37 Kolbach D N, Neumann H A, Prins M H. Definition of the post-thrombotic syndrome, differences between existing classifications.  Eur J Vasc Endovasc Surg. 2005;  30 404-414
• 38 Villalta S, Bagatella P, Piccioli A, Lensing A WA, Prins M H, Prandoni P. Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome.  Haemostasis. 1994;  24(suppl 1) 57a (abst)
• 39 Kahn S R, Hirsch A, Shrier I. Effect of post-thrombotic syndrome on health-related quality of life after deep venous thrombosis.  Arch Intern Med. 2002;  162 1144-1148
• 40 Porter J M, Moneta G L. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease.  J Vasc Surg. 1995;  21 635-645
• 41 Bettmann M A, Paulin S. Leg phlebography: the incidence, nature, and modification of undesirable side effects.  Radiology. 1977;  122 101-104
• 42 Villalta S, Prandoni P, Cogo A et al.. The utility of non-invasive tests for detection of previous proximal-vein thrombosis.  Thromb Haemost. 1995;  73 592-596
• 43 Carter C J. Incidence of post-phlebitic syndrome after streptokinase therapy for deep vein thrombosis.  Am J Med. 1990;  89 697-698
• 44 Shami S K, Shields D A, Scurr J H, Coleridge Smith P D. Leg ulceration in venous disease.  Postgrad Med J. 1992;  68 779-785
• 45 Coleridge Smith P D, Thomas P, Scurr J H, Dormandy J A. Causes of venous ulceration: a new hypothesis.  BMJ. 1988;  296 1726-1727
• 46 Lindhagen A, Bergqvist D, Hallböök T, Efsing H O. Venous function five to eight years after clinically suspected deep venous thrombosis.  Acta Med Scand. 1985;  217 389-395
• 47 Markel A, Manzo R A, Bergelin R O, Strandness D E. Valvular reflux after deep vein thrombosis: incidence and time of occurrence.  J Vasc Surg. 1992;  15 377-384
• 48 Franzeck U K, Schalch I, Bollinger A. On the relationship between changes in the deep veins evaluated by Duplex sonography and the postthrombotic syndrome 12 years after deep vein thrombosis.  Thromb Haemost. 1997;  77 1109-1112
• 49 Singh H, Masuda E M. Comparing short-term outcomes of femoral-popliteal and iliofemoral deep venous thrombosis: early lysis and development of reflux.  Ann Vasc Surg. 2005;  19 74-79
• 50 Haenen J H, Janssen M C, Wollersheim H et al.. The development of postthrombotic syndrome in relationship to venous reflux and calf muscle pump dysfunction at 2 years after the onset of deep venous thrombosis.  J Vasc Surg. 2002;  35 1184-1189
• 51 Prandoni P, Frulla M, Sartor D, Concolato A, Girolami A. Vein abnormalities and the post-thrombotic syndrome.  J Thromb Haemost. 2005;  3 401-402
• 52 Van Dongen C J, Prandoni P, Frulla M, Marchiori A, Prins M H, Hutten B A. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome.  J Thromb Haemost. 2005;  3 939-942
• 53 Ageno W, Piantanida E, Dentali F et al.. Body mass index is associated with the development of the post-thrombotic syndrome.  Thromb Haemost. 2003;  89 305-309
• 54 Hafner J, Bounameaux H, Burg G, Brunner U. Management of venous leg ulcers.  Vasa. 1996;  25 161-167
• 55 Evers E J, Wuppermann T. Effect of different compression therapies on the reflux in deep veins with a post-thrombotic syndrome.  Vasa. 1999;  28 19-23
• 56 Erickson C A, Lanza D J, Karp D L et al.. Healing of venous ulcers in an ambulatory care program: the roles of chronic venous insufficiency and patients compliance.  J Vasc Surg. 1995;  22 629-636
• 57 Milne A A, Ruckley C V. The clinical course of patients following extensive deep venous thrombosis.  Eur J Vasc Surg. 1994;  8 56-59
• 58 Prandoni P, Lensing A WA, Prins M H, Bagatella P, Scudeller A, Girolami A. Which is the outcome of the post-thrombotic syndrome?.  Thromb Haemost. 1999;  82 1196-1197
• 59 Kahn S R, Elman E, Rodger M A, Wells P S. Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicians and patients.  J Thomb Haemost. 2003;  1 500-506
• 60 Kahn S R, Azoulay L, Hirsch A, Haber M, Strulovitch C, Shrier I. Effect of graduated elastic compression stockings on leg symptoms and signs during exercise in patients with deep venous thrombosis: a randomized cross-over trial.  J Thomb Haemost. 2003;  1 494-499
• 61 Colgan M P, Dormandy J A, Jones P W, Schraibman I G, Shanik D G, Young R A. Oxpentifylline treatment of venous ulcers of the leg.  BMJ. 1990;  300 972-975
• 62 Layton A M, Ibbotson S H, Davies J A, Goodfield M J. Randomized trial of oral aspirin for chronic venous leg ulcer.  Lancet. 1994;  344 164-165
• 63 Rudofsky G. Intravenous prostaglandin E1 in the treatment of venous ulcers-a double-blind, placebo-controlled trial.  Vasa. 1989;  28(suppl) 39-43
• 64 Salim A S. Role of sulphydril-containing agents in the management of venous (varicose) ulceration. A new approach.  Clin Exp Dermatol. 1992;  17 427-432
• 65 Salim A S. The role of oxygen-derived free radicals in the management of venous (varicose) ulceration. A new approach.  World J Surg. 1991;  15 264-269
• 66 Coccheri S, Scandotto G, Agnelli G, Aloisi D, Palazzini E, Zamboni V. Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers.  Thromb Haemost. 2002;  87 947-952
• 67 Ginsberg J S, Magier D, Mackinnon B, Gent M, Hirsh J. Intermittent compression units for severe post-phlebitic syndrome: a randomised crossover study.  Can Med Assoc J. 1999;  160 1303-1306
• 68 Burnand K, Clemenson G, Morland M, Jarret P E, Browse N L. Venous lipodermatosclerosis: treatment by fibrinolytic enhancement and elastic compression.  BMJ. 1980;  280 7-11
• 69 de Jongste A B, Jonker J JC, Huisman M V, ten Cate J W, Azar A J. A double blind three center clinical trial on the short-term efficacy of 0-(β-hydroxyethyl)-rutosides in patients with post-thrombotic syndrome.  Thromb Haemost. 1989;  62 826-829
• 70 Frulla M, Marchiori A, Sartor D et al.. Elastic stockings, hydroxyethylrutosides or both for the treatment of post-thrombotic syndrome.  Thromb Haemost. 2005;  93 183-185
• 71 Baste J C, Midy F. Surgery for post-thrombotic syndrome of the lower limbs.  Rev Prat. 1994;  44 781-785
• 72 Gloviczki P, Bergan J J, Rhodes J M 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;  29 489-502
• 73 Perrin M, Hiltbrand B, Bayon J M. Results of valvuloplasty in patients presenting deep venous insufficiency and recurring ulceration.  Ann Vasc Surg. 1999;  13 524-532
• 74 Goldhaber S Z, Buring J E, Lipnick R J, Hennekens C H. Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis.  Am J Med. 1984;  76 393-397
• 75 Rogers L Q, Lutcher C L. Streptokinase therapy for deep vein thrombosis: a comprehensive review of the English literature.  Am J Med. 1990;  88 389-395
• 76 Kakkar V V, Lawrence D. Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis.  Am J Surg. 1985;  150 54-63
• 77 Lensing A WA, Hirsh J. Rationale and results of thrombolytic therapy for deep-vein thrombosis. In: Berstein EF Vascular Diagnosis. St. Louis, MO; Mosby-Year Book 1993: 875-879
• 78 Sidorov J. Streptokinase vs heparin for deep venous thrombosis. Can lytic therapy be justified?.  Arch Intern Med. 1989;  149 1841-1845
• 79 Büller H R, Agnelli G, Hull R D, Hyers T M, Prins M H, Raskob G E. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126(3 Suppl) 4015-4285
• 80 Partsch H, Kaulich M, Mayer W. Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome.  Int Angiol. 2004;  23 206-212
• 81 Milne A A, Ruckley C V. The clinical course of patients following extensive deep venous thrombosis.  Eur J Vasc Surg. 1994;  8 56-59
• 82 Prandoni P, Lensing A WA, Prins M H, Bagatella P, Scudeller A, Girolami A. Which is the outcome of the post-thrombotic syndrome?.  Thromb Haemost. 1999;  82 1196-1197