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Table 1. 
Clinical Features of Postthrombotic Syndrome
Clinical Features of Postthrombotic Syndrome
Table 2. 
Clinical Scales for the Diagnosis of Postthrombotic Syndrome
Clinical Scales for the Diagnosis of Postthrombotic Syndrome
Table 3. 
Prospective Studies of the Frequency of Postthrombotic Syndrome After Symptomatic DVT
Prospective Studies of the Frequency of Postthrombotic Syndrome After Symptomatic DVT
Table 4. 
Prospective Studies of the Frequency of Postthrombotic Syndrome in Patients Screened for Asymptomatic DVT
Prospective Studies of the Frequency of Postthrombotic Syndrome in Patients Screened for Asymptomatic DVT
Table 5. 
Prospective Studies of the Frequency of Postthrombotic Syndrome After Thrombolysis for Symptomatic DVT*
Prospective Studies of the Frequency of Postthrombotic Syndrome After Thrombolysis for Symptomatic DVT*
Table 6. 
Grades of Recommendations*
Grades of Recommendations*
1.
Prandoni  PLensing  AWCogo  A  et al.  The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;1251- 7
PubMedArticle
2.
Brandjes  DPMBüller  HRHeijboer  H  et al.  Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349759- 762
PubMedArticle
3.
Kahn  SRSolymoss  SLamping  DLAbenhaim  L Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality of life. J Gen Intern Med. 2000;15425- 429
PubMedArticle
4.
Kurz  XKahn  SRAbenhaim  L  et al.  Chronic venous disorders of the leg: epidemiology, outcomes, diagnosis and management: summary of an evidence-based report of the VEINES task force. Int Angiol. 1999;1883- 102
PubMed
5.
Bernardi  EPrandoni  P The post-thrombotic syndrome. Curr Opin Pulm Med. 2000;6335- 342
PubMedArticle
6.
Hopkins  NFWolfe  JH ABC of vascular diseases: deep venous insufficiency and occlusion. BMJ. 1992;304107- 110
PubMedArticle
7.
Ackroyd  JSBrowse  NL The investigation and surgery of the post-thrombotic syndrome. J Cardiovasc Surg (Torino). 1986;275- 16
PubMed
8.
Negus  D The post-thrombotic syndrome. Ann R Coll Surg Engl. 1970;4792- 105
PubMed
9.
Markel  AManzo  RABergelin  ROStrandness  DE  Jr Valvular reflux after deep vein thrombosis: incidence and time of occurrence. J Vasc Surg. 1992;15377- 382
PubMedArticle
10.
Franzeck  UKSchalch  IBollinger  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;771109- 1112
PubMed
11.
Franzeck  UKSchalch  IJäger  KASchneider  EGrimm  JBollinger  A Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zurich study). Circulation. 1996;9374- 79
PubMedArticle
12.
Lindhagen  ABergqvist  DHallböök  TEfsing  HO Venous function five to eight years after clinically suspected deep venous thrombosis. Acta Med Scand. 1985;217389- 395
PubMedArticle
13.
Haenen  JHJanssen  MCvan 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;291071- 1076
PubMedArticle
14.
Prandoni  PVillalta  SBagatella  P  et al.  The clinical course of deep-vein thrombosis: prospective long-term follow-up of 528 symptomatic patients. Haematologica. 1997;82423- 428
PubMed
15.
Beyth  RJCohen  AMLandefeld  CS Long-term outcomes of deep-vein thrombosis. Arch Intern Med. 1995;1551031- 1037
PubMedArticle
16.
McColl  MDEllison  JGreer  IATait  RCWalker  ID Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol. 2000;108272- 274
PubMedArticle
17.
Saarinen  JSisto  TLaunkka  JSalenius  J-PTarkka  M Late sequelae of acute deep venous thrombosis: evaluation five and ten years after. Phlebology. 1995;10106- 109
18.
Browse  NLClemenson  GThomas  ML Is the postphlebitic leg always postphlebitic? relation between phlebographic appearances of deep-vein thrombosis and late sequelae. BMJ. 1980;2811167- 1170
PubMedArticle
19.
Mohr  DNSilverstein  MDHeit  JAPetterson  TMO'Fallon  WMMelton III  LJ The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc. 2000;751249- 1256
PubMedArticle
20.
Meissner  MHCaps  MTZierler  BK  et al.  Determinants of chronic venous disease after acute deep venous thrombosis. J Vasc Surg. 1998;28826- 833
PubMedArticle
21.
Monreal  MMartorell  ACallejas  JM  et al.  Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study. J Intern Med. 1993;233233- 238
PubMedArticle
22.
Lindner  DJEdwards  JMPhinney  ESTaylor  LM  JrPorter  JM Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis. J Vasc Surg. 1986;4436- 442
PubMedArticle
23.
Strandness  DE  JrLanglois  YCramer  MRandlett  AThiele  BL Long-term sequelae of acute venous thrombosis. JAMA. 1983;2501289- 1292
PubMedArticle
24.
Philbrick  JTBecker  DM Calf deep venous thrombosis: a wolf in sheep's clothing? Arch Intern Med. 1988;1482131- 2138
PubMedArticle
25.
Kakkar  VVLawrence  D Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis: a prospective study. Am J Surg. 1985;15054- 63
PubMed
26.
Schulman  SGranqvist  SJuhlin-Dannfelt  ALockner  D Long-term sequelae of calf vein thrombosis treated with heparin or low-dose streptokinase. Acta Med Scand. 1986;219349- 357
PubMedArticle
27.
Masuda  EMKessler  DMKistner  RLEklof  BSato  DT The natural history of calf vein thrombosis: lysis of thrombi and development of reflux. J Vasc Surg. 1998;2867- 74
PubMedArticle
28.
Saarinen  JKallio  TLehto  MHiltunen  SSisto  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;41441- 446
PubMed
29.
Haenen  JHWollersheim  HJanssen  MC  et al.  Evolution of deep venous thrombosis: a 2-year follow-up using duplex ultrasound scan and strain-gauge plethysmography. J Vasc Surg. 2001;34649- 655
PubMedArticle
30.
Meissner  MHCaps  MTBergelin  ROManzo  RAStrandness  DE  Jr Early outcome after isolated calf vein thrombosis. J Vasc Surg. 1997;26749- 756
PubMedArticle
31.
McLafferty  RBMoneta  GLPassman  MABrant  BMTaylor  LM  JrPorter  JM Late clinical and hemodynamic sequelae of isolated calf vein thrombosis. J Vasc Surg. 1998;2750- 57
PubMedArticle
32.
Ginsberg  JSGent  MTurkstra  F  et al.  Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study. Arch Intern Med. 2000;160669- 672
PubMedArticle
33.
Andersen  MWille-Jørgensen  P Late complications of asymptomatic deep venous thrombosis. Eur J Surg. 1991;157527- 530
PubMed
34.
Warwick  DPerez  JVickery  CBannister  G Does total hip arthroplasty predispose to chronic venous insufficiency? J Arthroplasty. 1996;11529- 533
PubMedArticle
35.
McNally  MAMcAlinden  MGO'Connell  BMMollan  RA Postphlebitic syndrome after hip arthroplasty: 43 patients followed at least 5 years. Acta Orthop Scand. 1994;65595- 598
PubMedArticle
36.
Siragusa  SBeltrametti  CBarone  MPiovella  F Clinical course and incidence of post-thrombophlebitic syndrome after profound asymptomatic deep vein thrombosis: results of a transverse epidemiologic study [in Italian]. Minerva Cardioangiol. 1997;4557- 66
PubMed
37.
Heit  JAElliott  CGTrowbridge  AA  et al.  Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;132853- 861
PubMedArticle
38.
Hull  RDPineo  GFStein  PD  et al.  Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med. 2001;135858- 869
PubMedArticle
39.
Davidson  BLLensing  AW Prolonged prophylaxis after joint replacement: another step sideways? Ann Intern Med. 2000;132914- 915
PubMedArticle
40.
Biguzzi  EMozzi  EAlatri  ATaioli  EMoia  MMannucci  PM The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors. Thromb Haemost. 1998;80575- 577
PubMed
41.
Wille-Jorgensen  PJorgensen  TAndersen  MKirchhoff  M Postphlebitic syndrome and general surgery: an epidemiologic investigation. Angiology. 1991;42397- 403
PubMedArticle
42.
Killewich  LABedford  GRBeach  KWStrandness  DE  Jr Spontaneous lysis of deep venous thrombi: rate and outcome. J Vasc Surg. 1989;989- 97
PubMedArticle
43.
Milne  AAStonebridge  PABradbury  AWRuckley  CV Venous function and clinical outcome following deep vein thrombosis. Br J Surg. 1994;81847- 849
PubMedArticle
44.
Porter  JMMoneta  GLInternational Consensus Committee on Chronic Venous Disease, Reporting standards in venous disease: an update. J Vasc Surg. 1995;21635- 645
PubMedArticle
45.
Villalta  SBagatella  PPiccioli  ALensing  AWAPrins  MHPrandoni  P Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome [abstract 158]. Haemostasis. 1994;24(suppl 1)157
46.
Rutherford  RBPadberg  FT  JrComerota  AJKistner  RLMeissner  MHMoneta  GL Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg. 2000;311307- 1312
PubMedArticle
47.
Coon  WWWillis III  PWKeller  JB Venous thromboembolism and other venous disease in the Tecumseh community health study. Circulation. 1973;48839- 846
PubMedArticle
48.
Anderson  FA  JrWheeler  HBGoldberg  RJ  et al.  A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med. 1991;151933- 938
PubMedArticle
49.
Silverstein  MDHeit  JAMohr  DNPetterson  TMO'Fallon  WMMelton III  LJ Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998;158585- 593
PubMedArticle
50.
Heit  JASilverstein  MDMohr  DN  et al.  The epidemiology of venous thromboembolism in the community. Thromb Haemost. 2001;86452- 463
PubMed
51.
Nordström  MLindblad  BBergqvist  DKjellström  T A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med. 1992;232155- 160
PubMedArticle
52.
Heit  JARooke  TWSilverstein  MD  et al.  Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg. 2001;331022- 1027
PubMedArticle
53.
Ginsberg  JSHirsh  JJulian  J  et al.  Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med. 2001;1612105- 2109
PubMedArticle
54.
Johnson  BFManzo  RABergelin  ROStrandness  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;21307- 312
PubMedArticle
55.
AbuRahma  AFStickler  DLRobinson  PA A prospective controlled study of the efficacy of short-term anticoagulation therapy in patients with deep vein thrombosis of the lower extremity. J Vasc Surg. 1998;28630- 637
PubMedArticle
56.
Francis  CWRicotta  JJEvarts  CMMarder  VJ Long-term clinical observations and venous functional abnormalities after asymptomatic venous thrombosis following total hip or knee arthroplasty. Clin Orthop. July1988;232271- 278
PubMed
57.
Mudge  MLeinster  SJHughes  LE A prospective 10-year study of the post-thrombotic syndrome in a surgical population. Ann R Coll Surg Engl. 1988;70249- 252
PubMed
58.
Bergqvist  DJendteg  SJohansen  LPersson  UÖdegaard  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;126454- 457
PubMedArticle
59.
Scott  TELaMorte  WWGorin  DRMenzoian  JO Risk factors for chronic venous insufficiency: a dual case-control study. J Vasc Surg. 1995;22622- 628
PubMedArticle
60.
Hafner  JKuhne  ASchar  B  et al.  Factor V Leiden mutation in postthrombotic and non-postthrombotic venous ulcers. Arch Dermatol. 2001;137599- 603
PubMed
61.
Gaber  YSiemens  HJSchmeller  W Resistance to activated protein C due to factor V Leiden mutation: high prevalence in patients with post-thrombotic leg ulcers. Br J Dermatol. 2001;144546- 548
PubMedArticle
62.
Harrison  MBGraham  IDFriedberg  ELorimer  EOttawa-Carleton Regional Leg Ulcer Team, A regional planning study: assessing the population with leg and foot ulcers. Can Nurse. 2001;9718- 23
PubMed
63.
Bosanquet  N Costs of venous ulcers: from maintenance therapy to investment programmes. Phlebology. 1992;7(suppl 1)44- 46
64.
Van den Oever  RHepp  BDebbaut  BSimon  I Socio-economic impact of chronic venous insufficiency: an underestimated public health problem. Int Angiol. 1998;17161- 167
PubMed
65.
Abenhaim  LKurz  XVEINES Group, The VEINES study (VEnous Insufficiency Epidemiologic and Economic Study): an international cohort study on chronic venous disorders of the leg. Angiology. 1997;4859- 66
PubMedArticle
66.
Phillips  TStanton  BProvan  ALew  R A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. J Am Acad Dermatol. 1994;3149- 53
PubMedArticle
67.
Lamping  DL Measuring health-related quality of life in venous disease: practical and scientific considerations. Angiology. 1997;4851- 57
PubMedArticle
68.
Patrick  DLDeyo  RA Generic and disease-specific measures in assessing health status and quality of life. Med Care. 1989;27(3, suppl)S217- S232
PubMedArticle
69.
Ware  JKosinski  MKeller  SD SF-36 ® Physical and Mental Health Summary Scales: A User's Manual.  Boston, Mass Health Institute, New England Medical Center1994;
70.
O'Donnell  TF  JrBrowse  NLBurnand  KGThomas  ML The socioeconomic effects of an iliofemoral venous thrombosis. J Surg Res. 1977;22483- 488
PubMedArticle
71.
Lamping  DLSchroter  SKurz  XKahn  SRAbenhaim  L Evaluation of outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patient-reported measure of symptoms and quality of life. J Vasc Surg. 2003;37410- 419
PubMedArticle
72.
Kahn  SRHirsch  AShrier  I Effect of post-thrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med. 2002;1621144- 1148
PubMedArticle
73.
Geerts  WHHeit  JAClagett  GP  et al.  Prevention of venous thromboembolism. Chest. 2001;119(suppl 1)132S- 175S
PubMedArticle
74.
Arnold  DMKahn  SRShrier  I Missed opportunities for prevention of venous thromboembolism: an evaluation of the use of thromboprophylaxis guidelines. Chest. 2001;1201964- 1971
PubMedArticle
75.
Goldhaber  SZVisani  LDe Rosa  M Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;3531386- 1389
PubMedArticle
76.
Stratton  MAAnderson  FABussey  HI  et al.  Prevention of venous thromboembolism: adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients. Arch Intern Med. 2000;160334- 340
PubMedArticle
77.
Bratzler  DWRaskob  GEMurray  CKBumpus  LJPiatt  DS Underuse of venous thromboembolism prophylaxis for general surgery patients: physician practices in the community hospital setting. Arch Intern Med. 1998;1581909- 1912
PubMedArticle
78.
Turpie  AGGGallus  ASHoek  JAPentasaccharide Investigators, A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344619- 625
PubMedArticle
79.
Turpie  AGGBauer  KAEriksson  BILassen  MR Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. 2002;3591721- 1726
PubMedArticle
80.
Lassen  MRBauer  KAEriksson  BITurpie  AGG Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002;3591715- 1720
PubMedArticle
81.
Eriksson  BIBauer  KALassen  MRTurpie  AGG Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001;3451298- 1304
PubMedArticle
82.
Bauer  KAEriksson  BILassen  MRTurpie  AGG Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001;3451305- 1310
PubMedArticle
83.
Heit  JAColwell  CWFrancis  CW  et al.  Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study. Arch Intern Med. 2001;1612215- 2221
PubMedArticle
84.
Lee  AAgnelli  GBüller  H  et al.  Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation. 2001;10474- 78
PubMedArticle
85.
Cogo  ABernardi  EPrandoni  P  et al.  Acquired risk factors for deep-vein thrombosis in symptomatic outpatients. Arch Intern Med. 1994;154164- 168
PubMedArticle
86.
Kearon  CGent  MHirsh  J  et al.  A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340901- 907
PubMedArticle
87.
Schulman  S Optimal duration of oral anticoagulant therapy in venous thromboembolism. Thromb Haemost. 1997;78693- 698
PubMed
88.
Couturaud  FKearon  C Treatment of deep vein thrombosis. Semin Vasc Med. 2001;143- 54Article
89.
Wells  PSForster  AJ Thrombolysis in deep vein thrombosis: is there still an indication? Thromb Haemost. 2001;86499- 508
PubMed
90.
Schweizer  JKirch  WKoch  R  et al.  Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000;361336- 1343
PubMedArticle
91.
Elliot  MSImmelman  EJJeffery  P  et al.  A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal venous thrombosis: an interim report of a prospective trial. Br J Surg. 1979;66838- 843
PubMedArticle
92.
Arnesen  HHøiseth  ALy  B Streptokinase of heparin in the treatment of deep vein thrombosis: follow-up results of a prospective study. Acta Med Scand. 1982;21165- 68
PubMedArticle
93.
Turpie  AGLevine  MNHirsh  J  et al.  Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis: results of a randomized trial. Chest. 1990;97(4, suppl)172S- 175S
PubMed
94.
Common  HHSeaman  AJRösch  JPorter  JMDotter  CT Deep vein thrombosis treated with streptokinase or heparin: follow-up of a randomized study. Angiology. 1976;27645- 654
PubMedArticle
95.
Schulman  SLockner  DGranqvist  SBratt  GPaul  CNyman  D A comparative randomized trial of low-dose versus high-dose streptokinase in deep vein thrombosis of the thigh. Thromb Haemost. 1984;51261- 265
PubMed
96.
Goldhaber  SZBuring  JELipnick  RJHennekens  CH Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med. 1984;76393- 397
PubMedArticle
97.
Mewissen  MWSeabrook  GRMeissner  MHCynamon  JLabropoulos  NHaughton  SH Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999;21139- 49
PubMedArticle
98.
Goldhaber  SZMeyerovitz  MFGreen  D  et al.  Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis. Am J Med. 1990;88235- 240
PubMedArticle
99.
O'Donnell  TF  JrRosenthal  DACallow  ADLedig  BL Effect of elastic compression on venous hemodynamics in postphlebitic limbs. JAMA. 1979;2422766- 2768
PubMedArticle
100.
Pierson  SPierson  DSwallow  RJohnson  G  Jr Efficacy of graded elastic compression in the lower leg. JAMA. 1983;249242- 243
PubMedArticle
101.
Jones  NAWebb  PJRees  RIKakkar  VV A physiological study of elastic compression stockings in venous disorders of the leg. Br J Surg. 1980;67569- 572
PubMedArticle
102.
Noyes  LDRice  JCKerstein  MD Hemodynamic assessment of high-compression hosiery in chronic venous disease. Surgery. 1987;102813- 815
PubMed
103.
Evers  EJWuppermann  T Effect of different compression therapies on the reflux in deep veins with a post-thrombotic syndrome. Vasa. 1999;2819- 23
PubMedArticle
104.
Benkö  TCooke  EAMcNally  MAMollan  RAB Graduated compression stockings: knee length or thigh length. Clin Orthop. February2001;383197- 203
PubMedArticle
105.
Kahn  SRElman  ERRodger  MAWells  PS Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicans and patients. J Thromb Haemost. 2003;1500- 506Article
106.
Ginsberg  JSBrill-Edwards  PKowalchuk  GHirsh  J Intermittent compression units for the postphlebitic syndrome: a pilot study. Arch Intern Med. 1989;1491651- 1652
PubMedArticle
107.
Ginsberg  JSMagier  DMacKinnon  BGent  MHirsh  J Intermittent compression units for severe post-phlebitic syndrome: a randomized crossover study. CMAJ. 1999;1601303- 1306
PubMed
108.
Weingarten  MS State-of-the-art treatment of chronic venous disease. Clin Infect Dis. 2001;32949- 954
PubMedArticle
109.
Alguire  PCMathes  BM Chronic venous insufficiency and venous ulceration. J Gen Intern Med. 1997;12374- 383
PubMedArticle
110.
Gilliland  ELWolfe  JHN ABC of vascular diseases: leg ulcers. BMJ. 1991;303776- 779
PubMedArticle
111.
Cullum  NNelson  EAFletcher  AWSheldon  TA Compression for venous leg ulcers. Cochrane Database Syst Rev. 2001;(2)CD000265
112.
Krasner  D Painful venous ulcers: themes and stories about their impact on quality of life. Ostomy Wound Manage. 1998;4438- 49
PubMed
113.
Smith  JJGuest  MGGreenhalgh  RMDavies  AH Measuring the quality of life in patients with venous ulcers. J Vasc Surg. 2000;31642- 649
PubMedArticle
114.
Ruckley  CV Socioeconomic impact of chronic venous insufficiency and leg ulcers. Angiology. 1997;4867- 69
PubMedArticle
115.
Diehm  CTrampisch  HJLange  SSchmidt  C Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet. 1996;347292- 294
PubMedArticle
116.
Pittler  MHErnst  E Horse-chestnut seed extract for chronic venous insufficiency: a criteria-based systematic review. Arch Dermatol. 1998;1341356- 1360
PubMedArticle
117.
Guyatt  GSchuñemann  HCook  DJaeschke  RPauker  SBucher  H Grades of recommendation for antithrombotic agents. Chest. 2001;119(1, suppl)3S- 7S
PubMedArticle
118.
Kahn  SRDucruet  TJohri  Mfor the Venous Thrombosis Outcomes (VETO) Study Investigators, Resource utilisation and loss of productivity during the 4 months following a diagnosis of deep venous thrombosis [abstract]. J Thromb Haemost. 2003;1(7, suppl 1)abstract 181.
Review Article
January 12, 2004

Relationship Between Deep Venous Thrombosis and the Postthrombotic Syndrome

Author Affiliations

From the Department of Medicine, McGill University, Center for Clinical Epidemiology & Community Studies, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec (Dr Kahn); and Department of Medicine, McMaster University, McMaster University Medical Center, Hamilton, Ontario (Dr Ginsberg). The authors have no relevant financial interest in this article.

Arch Intern Med. 2004;164(1):17-26. doi:10.1001/archinte.164.1.17
Abstract

The postthrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). Clinically, PTS is characterized by chronic, persistent pain, swelling, and other signs in the affected limb. Rarely, ulcers may develop. Because of its prevalence, severity, and chronicity, PTS is burdensome and costly. Preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and minimizing the risk of ipsilateral DVT recurrence are likely to reduce the risk of development of PTS. Daily use of compression stockings after DVT might reduce the incidence and severity of PTS, but consistent and convincing data about their effectiveness are not available. Future research should focus on standardizing diagnostic criteria for PTS, identifying patients at high risk for PTS, and rigorously evaluating the role of thrombolysis in preventing PTS and of compression stockings in preventing and treating PTS. In addition, novel therapies should be sought and evaluated.

The postthrombotic syndrome (PTS) is a chronic condition that develops in 20% to 50% of patients within 1 to 2 years of symptomatic deep venous thrombosis (DVT). A severe form, which can include venous ulcers, occurs in one quarter to one third of patients with PTS.1,2 Because of its prevalence and chronicity, PTS is costly to society and is a cause of substantial patient morbidity.

In this article, we critically review the evidence informing current understanding of the pathophysiology, epidemiology, diagnosis, and management of PTS. The burden of PTS from both a patient and a societal perspective is discussed. Using standard criteria to grade the quality of the available evidence, we provide recommendations for the prevention and treatment of PTS. This article also acknowledges controversies in the field and key areas of ongoing and future research.

CLINICAL PRESENTATION AND PATHOPHYSIOLOGY OF PTS

Patients with PTS complain of pain, heaviness, swelling, cramps, itching, or tingling in the affected limb. Typically, symptoms are aggravated by standing or walking and improve with rest and recumbency. On physical examination, edema, telangiectasias, hyperpigmentation, eczema, and varicose collateral veins are often present. In severe cases, lipodermatosclerosis and ulceration may result36 (Table 1).

The pathophysiology of PTS is incompletely understood, but it is thought that the acute thrombus itself, associated mediators of inflammation, and the process of vein recanalization in the weeks after DVT induce damage to venous valves, leading to valvular incompetence (reflux). Valvular incompetence, persistent venous obstruction, or both cause venous hypertension,68 which leads to edema, tissue hypoxia, and, in some cases, skin ulceration.6,7 A number of clinical studies have suggested that valvular reflux in the proximal veins, particularly the popliteal vein, is associated with clinical manifestations of PTS.913 Therefore, preventing valve damage and reducing venous hypertension are likely to be important in preventing PTS.

FACTORS THAT PREDICT THE DEVELOPMENT OF PTS AFTER DVT
Recurrent DVT

The only clearly identified risk factor for PTS is recurrent, ipsilateral DVT, which increases the risk of PTS as much as 6-fold.1,1417 Recurrent DVT probably causes additional damage to already compromised venous valves and further venous outflow obstruction.

Characteristics of the Initial DVT

There is little correlation between the venographic severity of the initial thrombus and subsequent development of PTS.1,18 In some studies, the risk of PTS was higher in patients with proximal rather than distal (calf) DVT,1922 while in others the site of the initial thrombus did not influence the subsequent development of PTS.1,18,2325 In prospective studies, reported rates of PTS after distal DVT have ranged from 20% to 80%.2531 Hence, calf DVT is associated with a significant risk of subsequent PTS.

Asymptomatic DVT

Whether asymptomatic DVT (ie, detected by routine screening) leads to PTS is controversial. One study found that the frequency of PTS 2 to 7 years after hip or knee arthroplasty was similarly low (approximately 5%) in patients whose routine predischarge venogram showed proximal DVT, calf DVT, or no DVT.32 All patients with DVT received 6 to 12 weeks of anticoagulant therapy. Other investigators have also found low rates of PTS after asymptomatic DVT.33,34 Conversely, some groups have shown that as many as 25% to 33% of patients with asymptomatic DVT develop PTS.35,36 Differences in patient selection, study design, and definition of PTS may explain these discrepant results, but if confirmed, this would support the clinical relevance of asymptomatic DVT in studies of thromboprophylaxis37 and would provide a rationale for reducing the risk of such thrombi.38,39

Patient Characteristics

In prospective studies, clinical features such as delay in initiating treatment for DVT; risk factors for thrombosis; family history of thrombosis; protein C, protein S, or antithrombin deficiency; or the presence of the lupus anticoagulant have not been found to increase the risk of developing PTS.1,14 In retrospective studies, factors predictive of PTS were increasing age, female sex, hormone therapy, varicose veins, abdominal surgery, and increased body mass index.40,41

DIAGNOSIS OF PTS

There is no gold standard test for the diagnosis of PTS. In patients with objectively confirmed DVT and a typical clinical presentation, PTS is usually the correct diagnosis. As it usually takes 3 to 6 months after acute DVT for the initial pain and swelling to resolve, a diagnosis of PTS should be deferred until after this time. Objective evidence of venous valvular incompetence by Doppler ultrasound or by plethysmography helps to confirm the diagnosis in symptomatic patients.10,11,20,25,42 However, a diagnosis of PTS should not be made in the absence of clinical symptoms; while most patients with symptomatic PTS have valvular incompetence, many with valvular incompetence do not have PTS.43

Three clinical scales for the diagnosis of PTS are available32,44,45 and have been used in a number of clinical studies. They are presented in detail in Table 2.32,4446

IMPACT OF PTS
Population-Based Studies: Incidence and Prevalence

The prevalence of PTS is influenced by the incidence of DVT. Despite advances in its prevention and treatment, the annual incidence of venous thromboembolism (VTE) (ie, DVT and pulmonary embolism) has not decreased and is 1.0 to 1.6 per 1000 persons per year, with a per-person lifetime incidence of 2% to 5%.4751 Approximately 250 000 new cases of VTE occur in the United States each year.48 The population burden of PTS is difficult to estimate because of varying definitions of PTS and a tendency to undercode chronic conditions. In a recent study, cumulative rates of venous stasis were 7.3% at 1 year, 14.3% at 5 years, 19.7% at 10 years, and 26.8% at 20 years after DVT; the cumulative risk of ulcer was 3.7% by 20 years.19 It is estimated that more than one quarter of the at least 170 000 new cases of venous stasis syndrome per year represent PTS.52

Clinical Studies: Frequency of PTS After DVT

The frequency of PTS after objectively diagnosed DVT is difficult to estimate. Many studies have used surrogate end points such as reflux or abnormal results of venography without consideration of clinical symptoms and signs, and few have used validated PTS scores.

Nonetheless, a few prospective studies have provided key information on the frequency of PTS after symptomatic DVT. In a longitudinal cohort study of patients with a first episode of acute symptomatic DVT, Prandoni et al1 found that the cumulative incidence of PTS was 17.3% after 1 year (severe in 3%), 23% after 2 years, 28% after 5 years (severe in 9%), and 29% after 8 years. In a subsequent trial to evaluate the use of compression stockings to prevent PTS in patients with symptomatic proximal DVT, mild to moderate PTS occurred in 20% of patients assigned to stockings and in 47% of controls, and severe PTS occurred in 11% and 23%, respectively.2 The frequency of PTS in the stockings group was similar to that in the study by Prandoni et al, in which all patients were encouraged to wear compression stockings. In both studies, most cases of PTS occurred within 2 years of DVT. In contrast, in a recent study by Ginsberg and colleagues,53 27% of patients (none of whom used stockings) had developed PTS by 1 year after a first episode of symptomatic proximal DVT, but among patients who were free of PTS 1 year after DVT, only 5% subsequently developed PTS (average follow-up, 55 months). However, the Ginsberg et al study used stricter diagnostic criteria for PTS: in addition to symptoms, objective demonstration of valvular incompetence was required.

In summary, the frequency of PTS after symptomatic DVT ranges from 15% to 50%. In most cases, PTS develops within 1 to 2 years after DVT. Severe PTS occurs in 5% to 10% of patients after DVT. Table 3 provides a synopsis of prospective studies of the frequency of PTS after symptomatic DVT,1,2,10,20,21,23,25,2729,5355 and Table 4, after asymptomatic DVT.3236,53,56,57

Cost of PTS

Although there is little direct-cost information available, PTS undoubtedly incurs high direct costs and indirect costs such as loss of productivity. A Swedish study estimated that the average cost of treating PTS was US $4700, or 75% of the cost of treating the primary DVT.58 Extrapolations can be made from the costs of treating chronic venous insufficiency and venous ulcers, since a proportion of these cases represent PTS.52,5961 In a recent Canadian study, patients with venous ulcers composed 6% of home care clientele but consumed 18% of supply expenditures, and the annual cost of their care was more than $1 million.62 The direct cost of treating chronic venous insufficiency exceeds $300 million per year in the United States,52 with similar costs in Britain, Belgium, France, Germany, Italy, and Spain.4,6365 The indirect costs of PTS are also likely to be significant, since PTS often affects persons of working age. It is estimated that, for leg ulcers, 2 million workdays are lost annually in the United States.66

Impact of PTS on Quality of Life

For chronic conditions such as PTS, assessment of quality of life can provide important information on burden of illness.3,67,68 Despite the availability of easy-to-use, validated measures of generic quality of life,68,69 few studies have quantified the long-term impact of DVT, or of PTS, on quality of life. An early study showed that almost 90% of patients were disabled and unable to work because of leg symptoms 10 or more years after iliofemoral DVT.70 In a study of patients who had DVT 6 to 8 years earlier, those with PTS had poorer health perceptions, worse physical functioning, and more severe role limitations, as measured by the SF-36 Health Survey quality-of-life questionnaire.15 Recently, in the course of conducting the Venous Insufficiency Epidemiologic and Economic Study (VEINES), our group developed and validated the VEINES-QOL/Sym questionnaire, a venous disease–specific quality-of-life measure,71 and showed that by 2 years after DVT, patients with PTS had significantly worse quality of life than those without PTS, and scores worsened with increasing severity of PTS.72

MANAGEMENT OF PTS
Preventing PTS

Thromboprophylaxis. Postthrombotic syndrome can be averted with the use of thromboprophylaxis to prevent DVT in high-risk patients and settings, as recommended in regularly updated consensus guidelines.73 However, audits consistently demonstrate that thromboprophylaxis is underused.7477 Furthermore, existing thromboprophylaxis regimens do not eliminate the risk of VTE.73 New antithrombotic drugs may be more effective than existing regimens in preventing VTE in high-risk patients.7884 Since the publication of the last consensus guidelines in 2001,73 newer classes of drugs such as synthetic pentasaccharides have demonstrated promising results in phase 3 trials of VTE prevention when compared with conventional heparins.7982 Unfortunately, nearly 50% of VTE events occur unpredictably and therefore cannot be prevented with thromboprophylaxis.74,85 Hence, strategies that focus on preventing the development of PTS after DVT are more feasible and more likely to be effective in reducing the burden of PTS than are attempts to prevent the index DVT. Since ipsilateral DVT recurrence is a risk factor for PTS, preventing recurrent DVT by optimizing the intensity and duration of anticoagulation for an initial DVT, taking into account the patient's risk of recurrence and of bleeding,8688 is an important goal.

Role of Thrombolysis. The use of thrombolytic therapy in addition to heparin for the treatment of acute DVT leads to higher rates of vein patency and better preservation of valve function than does the use of heparin alone. However, there is no definitive evidence that thrombolysis leads to lower rates of PTS compared with the use of heparin and warfarin alone89 (Table 5).26,9095 Furthermore, thrombolytic trials or registries of treated patients have tended to ignore long-term outcomes such as PTS.89,9698 Large controlled trials of standard anticoagulation vs catheter-directed thrombolysis, which may be safer and more effective than systemic therapy,97 are required to definitively address this issue.

Elastic Compression Stockings. Graduated elastic compression stockings (ECSs) assist the calf muscle pump, reduce venous hypertension and reflux, and thereby reduce edema and improve tissue microcirculation.99103 Knee-length and thigh-length ECSs have equal physiologic effects, but the former are easier to apply and more comfortable.104

Notwithstanding their physiologic effects, data on the clinical effectiveness of ECSs in preventing PTS are scarce and inconclusive. Evidence supporting their effectiveness comes primarily from the trial by Brandjes et al2 of 194 patients with symptomatic proximal DVT. Patients were randomly allocated to daily use of 30– to 40–mm Hg knee-length ECSs for at least 2 years, or no stocking. Use of ECSs resulted in a decrease from 47% to 20% of mild or moderate PTS, and from 23% to 11% of severe PTS, diagnosed with the scale of Villalta et al45 (see Table 2). As a result of this trial, it has become common clinical practice to prescribe ECSs for patients with DVT, particularly proximal DVT.105 However, a recent randomized trial conducted by Ginsberg and colleagues53 showed no benefit of daily ECSs in preventing or treating PTS. This study used a more specific measure of PTS than that of Brandjes et al2 (see Table 2), and control patients wore sham stockings. Because of the small number of patients with PTS, benefit (or harm) of up to 30% compared with the control group could not be excluded. These results, while not definitive, question the generalizability of the results of the Brandjes et al study, which had unusually high rates of PTS in the control group and dramatic reductions in both relative and absolute risk of PTS in the stocking group.

Stockings are difficult to apply, uncomfortable, and expensive, and require replacement every few months. Because of the uncertainty regarding their value in preventing PTS after DVT, further research on their effectiveness is required.

Treating PTS

Available treatments for established PTS are limited. Regular use of ECSs may improve symptoms and swelling. Severe intractable PTS can be managed with long-term use of an intermittent compression extremity pump.106,107 Postthrombotic venous ulcers are managed with compression therapy, leg elevation, topical dressings, and sometimes surgery.4,108111 Ulcers are often recalcitrant and tend to recur,109 causing pain and suffering to patients112,113 and incurring high costs to society.66,114 The short-term use of "venoactive" medications such as horse chestnut seed extract or hydroxyethyl rutosides appears to be effective in reducing symptoms of chronic venous insufficiency115,116; however, their long-term effectiveness and safety and their value in patients with PTS are unknown. There is no proven role for the long-term use of diuretics to treat PTS-related edema.

RECOMMENDATIONS REGARDING PREVENTION AND TREATMENT OF PTS

The following recommendations for the prevention and treatment of PTS are based on our review of the literature. Levels of evidence, using an adaptation of the categories proposed by Guyatt et al117 in the sixth American College of Chest Physicians consensus conference on antithrombotic therapy (Table 6), are used when appropriate.

General Recommendations

  • Physicians should actively screen patients with DVT for PTS during follow-up.

The diagnosis of PTS should primarily be based on the presence of typical symptoms and signs, since objective evidence of venous valvular incompetence has low specificity for PTS. However, the presence of valvular incompetence helps to confirm the diagnosis of PTS (and rule out other conditions) in symptomatic patients.

Prevention of PTS

  • Prevention of the index DVT will prevent PTS.

  • Prevention of ipsilateral DVT recurrence is likely to decrease the risk of developing PTS and prevent worsening of PTS (grade 1C).

  • In patients with proximal DVT, the risk of developing PTS may be reduced with daily use of knee-length, 30– to 40–mm Hg ECSs (grade 2B).

  • The effects of ECSs after distal DVT and the optimal duration of ECS use are not known.

  • There is no convincing evidence that systemic thrombolysis prevents PTS (grades 2B and 2C). Catheter-directed thrombolysis requires further evaluation in properly designed trials before it is endorsed as being effective in reducing the risk of PTS.

Treatment of PTS

  • Compression stockings may reduce swelling in some patients with PTS and should be tried. Their benefit in this setting is extrapolated from studies of patients with chronic venous disease4 but has not been definitively shown in the setting of PTS.

  • Severe, intractable PTS can be improved with long-term use of an intermittent compression extremity pump (grade 1A). There is no proven role for venoactive medications or diuretics in the management of PTS.

FUTURE DIRECTIONS

Further work needs to be done to increase our understanding of PTS and to test potentially effective preventive and therapeutic interventions. The frequency of PTS in different DVT patient populations (asymptomatic vs symptomatic, proximal vs distal, thrombophilia) should be evaluated in prospective studies of consecutive patients, using a systematic approach to PTS diagnosis. Enumeration of the direct and indirect costs of PTS, identification of key factors that influence costs, and quantification of the impact of PTS on quality of life will allow better estimation of its population burden and more accurate evaluation of the cost-effectiveness of various preventive and therapeutic regimens. Large-scale controlled trials are needed to evaluate the effectiveness, optimal timing, strength, and duration of use of compression stockings in preventing and treating PTS. Multicenter trials of catheter-directed thrombolysis to prevent PTS in patients with extensive proximal DVT are also required. Finally, the value of venoactive agents, diuretics, and anti-inflammatory medications should be studied.

THE VENOUS THROMBOSIS OUTCOMES STUDY

The Venous Thrombosis Outcomes Study is an ongoing Canadian multicenter prospective cohort study being conducted by our group. Its objectives are to estimate the incidence and timing of PTS within 2 years after objectively confirmed DVT and to identify clinical and genetic risk factors that predict its development. Quality of life is being evaluated with the VEINES-QOL/Sym questionnaire,71 and direct and indirect costs of PTS are being quantified by means of data obtained from multiple sources (patient diaries, patient interviews, hospital chart, health insurance databases).118 This study will help to enumerate the patient and societal burden of PTS and will identify key variables that most influence quality of life and costs.

SUMMARY

Because of its prevalence, severity, and chronicity, PTS is costly and burdensome to patients and society. It is likely to become more prevalent, since the incidence of DVT has not decreased. The availability of newer, more effective antithrombotic agents may lead to a reduction in the future incidence of DVT, and thereby PTS, in certain settings. The overall frequency of PTS after symptomatic DVT ranges from 20% to 50%; severe PTS occurs in 5% to 10% of patients with DVT. Preventing ipsilateral DVT recurrence is likely to reduce the risk of PTS. There is no proven role for thrombolysis in preventing PTS. Daily use of graduated compression stockings after DVT may reduce the risk of PTS and may prevent the worsening of established PTS. Prevention of PTS is the key to reducing its morbidity, since, at present, treatment options for PTS are extremely limited.

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Article Information

Corresponding author: Susan R. Kahn MD, MSc, FRCPC, Department of Medicine, McGill University, Center for Clinical Epidemiology & Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste Catherine, Room A-127, Montreal, Quebec, Canada H3T 1E2 (e-mail: susan.kahn@mcgill.ca).

Accepted for publication January 24, 2003.

This work was supported in part by an unrestricted educational grant from Organon-Sanofi Synthelabo. Dr Kahn is a recipient of a Clinical Research Scientist Award from the Fonds de la Recherche en Santé du Québec, Montreal. Dr Ginsberg is a recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario, Toronto, and a Research Chair from the Canadian Institutes of Health Research/AstraZeneca, Ottawa, Ontario.

We thank Joan Sobel, PhD, for her help with development of the tables.

References
1.
Prandoni  PLensing  AWCogo  A  et al.  The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;1251- 7
PubMedArticle
2.
Brandjes  DPMBüller  HRHeijboer  H  et al.  Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349759- 762
PubMedArticle
3.
Kahn  SRSolymoss  SLamping  DLAbenhaim  L Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality of life. J Gen Intern Med. 2000;15425- 429
PubMedArticle
4.
Kurz  XKahn  SRAbenhaim  L  et al.  Chronic venous disorders of the leg: epidemiology, outcomes, diagnosis and management: summary of an evidence-based report of the VEINES task force. Int Angiol. 1999;1883- 102
PubMed
5.
Bernardi  EPrandoni  P The post-thrombotic syndrome. Curr Opin Pulm Med. 2000;6335- 342
PubMedArticle
6.
Hopkins  NFWolfe  JH ABC of vascular diseases: deep venous insufficiency and occlusion. BMJ. 1992;304107- 110
PubMedArticle
7.
Ackroyd  JSBrowse  NL The investigation and surgery of the post-thrombotic syndrome. J Cardiovasc Surg (Torino). 1986;275- 16
PubMed
8.
Negus  D The post-thrombotic syndrome. Ann R Coll Surg Engl. 1970;4792- 105
PubMed
9.
Markel  AManzo  RABergelin  ROStrandness  DE  Jr Valvular reflux after deep vein thrombosis: incidence and time of occurrence. J Vasc Surg. 1992;15377- 382
PubMedArticle
10.
Franzeck  UKSchalch  IBollinger  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;771109- 1112
PubMed
11.
Franzeck  UKSchalch  IJäger  KASchneider  EGrimm  JBollinger  A Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zurich study). Circulation. 1996;9374- 79
PubMedArticle
12.
Lindhagen  ABergqvist  DHallböök  TEfsing  HO Venous function five to eight years after clinically suspected deep venous thrombosis. Acta Med Scand. 1985;217389- 395
PubMedArticle
13.
Haenen  JHJanssen  MCvan 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;291071- 1076
PubMedArticle
14.
Prandoni  PVillalta  SBagatella  P  et al.  The clinical course of deep-vein thrombosis: prospective long-term follow-up of 528 symptomatic patients. Haematologica. 1997;82423- 428
PubMed
15.
Beyth  RJCohen  AMLandefeld  CS Long-term outcomes of deep-vein thrombosis. Arch Intern Med. 1995;1551031- 1037
PubMedArticle
16.
McColl  MDEllison  JGreer  IATait  RCWalker  ID Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol. 2000;108272- 274
PubMedArticle
17.
Saarinen  JSisto  TLaunkka  JSalenius  J-PTarkka  M Late sequelae of acute deep venous thrombosis: evaluation five and ten years after. Phlebology. 1995;10106- 109
18.
Browse  NLClemenson  GThomas  ML Is the postphlebitic leg always postphlebitic? relation between phlebographic appearances of deep-vein thrombosis and late sequelae. BMJ. 1980;2811167- 1170
PubMedArticle
19.
Mohr  DNSilverstein  MDHeit  JAPetterson  TMO'Fallon  WMMelton III  LJ The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc. 2000;751249- 1256
PubMedArticle
20.
Meissner  MHCaps  MTZierler  BK  et al.  Determinants of chronic venous disease after acute deep venous thrombosis. J Vasc Surg. 1998;28826- 833
PubMedArticle
21.
Monreal  MMartorell  ACallejas  JM  et al.  Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study. J Intern Med. 1993;233233- 238
PubMedArticle
22.
Lindner  DJEdwards  JMPhinney  ESTaylor  LM  JrPorter  JM Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis. J Vasc Surg. 1986;4436- 442
PubMedArticle
23.
Strandness  DE  JrLanglois  YCramer  MRandlett  AThiele  BL Long-term sequelae of acute venous thrombosis. JAMA. 1983;2501289- 1292
PubMedArticle
24.
Philbrick  JTBecker  DM Calf deep venous thrombosis: a wolf in sheep's clothing? Arch Intern Med. 1988;1482131- 2138
PubMedArticle
25.
Kakkar  VVLawrence  D Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis: a prospective study. Am J Surg. 1985;15054- 63
PubMed
26.
Schulman  SGranqvist  SJuhlin-Dannfelt  ALockner  D Long-term sequelae of calf vein thrombosis treated with heparin or low-dose streptokinase. Acta Med Scand. 1986;219349- 357
PubMedArticle
27.
Masuda  EMKessler  DMKistner  RLEklof  BSato  DT The natural history of calf vein thrombosis: lysis of thrombi and development of reflux. J Vasc Surg. 1998;2867- 74
PubMedArticle
28.
Saarinen  JKallio  TLehto  MHiltunen  SSisto  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;41441- 446
PubMed
29.
Haenen  JHWollersheim  HJanssen  MC  et al.  Evolution of deep venous thrombosis: a 2-year follow-up using duplex ultrasound scan and strain-gauge plethysmography. J Vasc Surg. 2001;34649- 655
PubMedArticle
30.
Meissner  MHCaps  MTBergelin  ROManzo  RAStrandness  DE  Jr Early outcome after isolated calf vein thrombosis. J Vasc Surg. 1997;26749- 756
PubMedArticle
31.
McLafferty  RBMoneta  GLPassman  MABrant  BMTaylor  LM  JrPorter  JM Late clinical and hemodynamic sequelae of isolated calf vein thrombosis. J Vasc Surg. 1998;2750- 57
PubMedArticle
32.
Ginsberg  JSGent  MTurkstra  F  et al.  Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study. Arch Intern Med. 2000;160669- 672
PubMedArticle
33.
Andersen  MWille-Jørgensen  P Late complications of asymptomatic deep venous thrombosis. Eur J Surg. 1991;157527- 530
PubMed
34.
Warwick  DPerez  JVickery  CBannister  G Does total hip arthroplasty predispose to chronic venous insufficiency? J Arthroplasty. 1996;11529- 533
PubMedArticle
35.
McNally  MAMcAlinden  MGO'Connell  BMMollan  RA Postphlebitic syndrome after hip arthroplasty: 43 patients followed at least 5 years. Acta Orthop Scand. 1994;65595- 598
PubMedArticle
36.
Siragusa  SBeltrametti  CBarone  MPiovella  F Clinical course and incidence of post-thrombophlebitic syndrome after profound asymptomatic deep vein thrombosis: results of a transverse epidemiologic study [in Italian]. Minerva Cardioangiol. 1997;4557- 66
PubMed
37.
Heit  JAElliott  CGTrowbridge  AA  et al.  Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;132853- 861
PubMedArticle
38.
Hull  RDPineo  GFStein  PD  et al.  Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med. 2001;135858- 869
PubMedArticle
39.
Davidson  BLLensing  AW Prolonged prophylaxis after joint replacement: another step sideways? Ann Intern Med. 2000;132914- 915
PubMedArticle
40.
Biguzzi  EMozzi  EAlatri  ATaioli  EMoia  MMannucci  PM The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors. Thromb Haemost. 1998;80575- 577
PubMed
41.
Wille-Jorgensen  PJorgensen  TAndersen  MKirchhoff  M Postphlebitic syndrome and general surgery: an epidemiologic investigation. Angiology. 1991;42397- 403
PubMedArticle
42.
Killewich  LABedford  GRBeach  KWStrandness  DE  Jr Spontaneous lysis of deep venous thrombi: rate and outcome. J Vasc Surg. 1989;989- 97
PubMedArticle
43.
Milne  AAStonebridge  PABradbury  AWRuckley  CV Venous function and clinical outcome following deep vein thrombosis. Br J Surg. 1994;81847- 849
PubMedArticle
44.
Porter  JMMoneta  GLInternational Consensus Committee on Chronic Venous Disease, Reporting standards in venous disease: an update. J Vasc Surg. 1995;21635- 645
PubMedArticle
45.
Villalta  SBagatella  PPiccioli  ALensing  AWAPrins  MHPrandoni  P Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome [abstract 158]. Haemostasis. 1994;24(suppl 1)157
46.
Rutherford  RBPadberg  FT  JrComerota  AJKistner  RLMeissner  MHMoneta  GL Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg. 2000;311307- 1312
PubMedArticle
47.
Coon  WWWillis III  PWKeller  JB Venous thromboembolism and other venous disease in the Tecumseh community health study. Circulation. 1973;48839- 846
PubMedArticle
48.
Anderson  FA  JrWheeler  HBGoldberg  RJ  et al.  A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med. 1991;151933- 938
PubMedArticle
49.
Silverstein  MDHeit  JAMohr  DNPetterson  TMO'Fallon  WMMelton III  LJ Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998;158585- 593
PubMedArticle
50.
Heit  JASilverstein  MDMohr  DN  et al.  The epidemiology of venous thromboembolism in the community. Thromb Haemost. 2001;86452- 463
PubMed
51.
Nordström  MLindblad  BBergqvist  DKjellström  T A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med. 1992;232155- 160
PubMedArticle
52.
Heit  JARooke  TWSilverstein  MD  et al.  Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg. 2001;331022- 1027
PubMedArticle
53.
Ginsberg  JSHirsh  JJulian  J  et al.  Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med. 2001;1612105- 2109
PubMedArticle
54.
Johnson  BFManzo  RABergelin  ROStrandness  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;21307- 312
PubMedArticle
55.
AbuRahma  AFStickler  DLRobinson  PA A prospective controlled study of the efficacy of short-term anticoagulation therapy in patients with deep vein thrombosis of the lower extremity. J Vasc Surg. 1998;28630- 637
PubMedArticle
56.
Francis  CWRicotta  JJEvarts  CMMarder  VJ Long-term clinical observations and venous functional abnormalities after asymptomatic venous thrombosis following total hip or knee arthroplasty. Clin Orthop. July1988;232271- 278
PubMed
57.
Mudge  MLeinster  SJHughes  LE A prospective 10-year study of the post-thrombotic syndrome in a surgical population. Ann R Coll Surg Engl. 1988;70249- 252
PubMed
58.
Bergqvist  DJendteg  SJohansen  LPersson  UÖdegaard  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;126454- 457
PubMedArticle
59.
Scott  TELaMorte  WWGorin  DRMenzoian  JO Risk factors for chronic venous insufficiency: a dual case-control study. J Vasc Surg. 1995;22622- 628
PubMedArticle
60.
Hafner  JKuhne  ASchar  B  et al.  Factor V Leiden mutation in postthrombotic and non-postthrombotic venous ulcers. Arch Dermatol. 2001;137599- 603
PubMed
61.
Gaber  YSiemens  HJSchmeller  W Resistance to activated protein C due to factor V Leiden mutation: high prevalence in patients with post-thrombotic leg ulcers. Br J Dermatol. 2001;144546- 548
PubMedArticle
62.
Harrison  MBGraham  IDFriedberg  ELorimer  EOttawa-Carleton Regional Leg Ulcer Team, A regional planning study: assessing the population with leg and foot ulcers. Can Nurse. 2001;9718- 23
PubMed
63.
Bosanquet  N Costs of venous ulcers: from maintenance therapy to investment programmes. Phlebology. 1992;7(suppl 1)44- 46
64.
Van den Oever  RHepp  BDebbaut  BSimon  I Socio-economic impact of chronic venous insufficiency: an underestimated public health problem. Int Angiol. 1998;17161- 167
PubMed
65.
Abenhaim  LKurz  XVEINES Group, The VEINES study (VEnous Insufficiency Epidemiologic and Economic Study): an international cohort study on chronic venous disorders of the leg. Angiology. 1997;4859- 66
PubMedArticle
66.
Phillips  TStanton  BProvan  ALew  R A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. J Am Acad Dermatol. 1994;3149- 53
PubMedArticle
67.
Lamping  DL Measuring health-related quality of life in venous disease: practical and scientific considerations. Angiology. 1997;4851- 57
PubMedArticle
68.
Patrick  DLDeyo  RA Generic and disease-specific measures in assessing health status and quality of life. Med Care. 1989;27(3, suppl)S217- S232
PubMedArticle
69.
Ware  JKosinski  MKeller  SD SF-36 ® Physical and Mental Health Summary Scales: A User's Manual.  Boston, Mass Health Institute, New England Medical Center1994;
70.
O'Donnell  TF  JrBrowse  NLBurnand  KGThomas  ML The socioeconomic effects of an iliofemoral venous thrombosis. J Surg Res. 1977;22483- 488
PubMedArticle
71.
Lamping  DLSchroter  SKurz  XKahn  SRAbenhaim  L Evaluation of outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patient-reported measure of symptoms and quality of life. J Vasc Surg. 2003;37410- 419
PubMedArticle
72.
Kahn  SRHirsch  AShrier  I Effect of post-thrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med. 2002;1621144- 1148
PubMedArticle
73.
Geerts  WHHeit  JAClagett  GP  et al.  Prevention of venous thromboembolism. Chest. 2001;119(suppl 1)132S- 175S
PubMedArticle
74.
Arnold  DMKahn  SRShrier  I Missed opportunities for prevention of venous thromboembolism: an evaluation of the use of thromboprophylaxis guidelines. Chest. 2001;1201964- 1971
PubMedArticle
75.
Goldhaber  SZVisani  LDe Rosa  M Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;3531386- 1389
PubMedArticle
76.
Stratton  MAAnderson  FABussey  HI  et al.  Prevention of venous thromboembolism: adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients. Arch Intern Med. 2000;160334- 340
PubMedArticle
77.
Bratzler  DWRaskob  GEMurray  CKBumpus  LJPiatt  DS Underuse of venous thromboembolism prophylaxis for general surgery patients: physician practices in the community hospital setting. Arch Intern Med. 1998;1581909- 1912
PubMedArticle
78.
Turpie  AGGGallus  ASHoek  JAPentasaccharide Investigators, A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344619- 625
PubMedArticle
79.
Turpie  AGGBauer  KAEriksson  BILassen  MR Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. 2002;3591721- 1726
PubMedArticle
80.
Lassen  MRBauer  KAEriksson  BITurpie  AGG Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002;3591715- 1720
PubMedArticle
81.
Eriksson  BIBauer  KALassen  MRTurpie  AGG Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001;3451298- 1304
PubMedArticle
82.
Bauer  KAEriksson  BILassen  MRTurpie  AGG Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001;3451305- 1310
PubMedArticle
83.
Heit  JAColwell  CWFrancis  CW  et al.  Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study. Arch Intern Med. 2001;1612215- 2221
PubMedArticle
84.
Lee  AAgnelli  GBüller  H  et al.  Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation. 2001;10474- 78
PubMedArticle
85.
Cogo  ABernardi  EPrandoni  P  et al.  Acquired risk factors for deep-vein thrombosis in symptomatic outpatients. Arch Intern Med. 1994;154164- 168
PubMedArticle
86.
Kearon  CGent  MHirsh  J  et al.  A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340901- 907
PubMedArticle
87.
Schulman  S Optimal duration of oral anticoagulant therapy in venous thromboembolism. Thromb Haemost. 1997;78693- 698
PubMed
88.
Couturaud  FKearon  C Treatment of deep vein thrombosis. Semin Vasc Med. 2001;143- 54Article
89.
Wells  PSForster  AJ Thrombolysis in deep vein thrombosis: is there still an indication? Thromb Haemost. 2001;86499- 508
PubMed
90.
Schweizer  JKirch  WKoch  R  et al.  Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000;361336- 1343
PubMedArticle
91.
Elliot  MSImmelman  EJJeffery  P  et al.  A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal venous thrombosis: an interim report of a prospective trial. Br J Surg. 1979;66838- 843
PubMedArticle
92.
Arnesen  HHøiseth  ALy  B Streptokinase of heparin in the treatment of deep vein thrombosis: follow-up results of a prospective study. Acta Med Scand. 1982;21165- 68
PubMedArticle
93.
Turpie  AGLevine  MNHirsh  J  et al.  Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis: results of a randomized trial. Chest. 1990;97(4, suppl)172S- 175S
PubMed
94.
Common  HHSeaman  AJRösch  JPorter  JMDotter  CT Deep vein thrombosis treated with streptokinase or heparin: follow-up of a randomized study. Angiology. 1976;27645- 654
PubMedArticle
95.
Schulman  SLockner  DGranqvist  SBratt  GPaul  CNyman  D A comparative randomized trial of low-dose versus high-dose streptokinase in deep vein thrombosis of the thigh. Thromb Haemost. 1984;51261- 265
PubMed
96.
Goldhaber  SZBuring  JELipnick  RJHennekens  CH Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med. 1984;76393- 397
PubMedArticle
97.
Mewissen  MWSeabrook  GRMeissner  MHCynamon  JLabropoulos  NHaughton  SH Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999;21139- 49
PubMedArticle
98.
Goldhaber  SZMeyerovitz  MFGreen  D  et al.  Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis. Am J Med. 1990;88235- 240
PubMedArticle
99.
O'Donnell  TF  JrRosenthal  DACallow  ADLedig  BL Effect of elastic compression on venous hemodynamics in postphlebitic limbs. JAMA. 1979;2422766- 2768
PubMedArticle
100.
Pierson  SPierson  DSwallow  RJohnson  G  Jr Efficacy of graded elastic compression in the lower leg. JAMA. 1983;249242- 243
PubMedArticle
101.
Jones  NAWebb  PJRees  RIKakkar  VV A physiological study of elastic compression stockings in venous disorders of the leg. Br J Surg. 1980;67569- 572
PubMedArticle
102.
Noyes  LDRice  JCKerstein  MD Hemodynamic assessment of high-compression hosiery in chronic venous disease. Surgery. 1987;102813- 815
PubMed
103.
Evers  EJWuppermann  T Effect of different compression therapies on the reflux in deep veins with a post-thrombotic syndrome. Vasa. 1999;2819- 23
PubMedArticle
104.
Benkö  TCooke  EAMcNally  MAMollan  RAB Graduated compression stockings: knee length or thigh length. Clin Orthop. February2001;383197- 203
PubMedArticle
105.
Kahn  SRElman  ERRodger  MAWells  PS Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicans and patients. J Thromb Haemost. 2003;1500- 506Article
106.
Ginsberg  JSBrill-Edwards  PKowalchuk  GHirsh  J Intermittent compression units for the postphlebitic syndrome: a pilot study. Arch Intern Med. 1989;1491651- 1652
PubMedArticle
107.
Ginsberg  JSMagier  DMacKinnon  BGent  MHirsh  J Intermittent compression units for severe post-phlebitic syndrome: a randomized crossover study. CMAJ. 1999;1601303- 1306
PubMed
108.
Weingarten  MS State-of-the-art treatment of chronic venous disease. Clin Infect Dis. 2001;32949- 954
PubMedArticle
109.
Alguire  PCMathes  BM Chronic venous insufficiency and venous ulceration. J Gen Intern Med. 1997;12374- 383
PubMedArticle
110.
Gilliland  ELWolfe  JHN ABC of vascular diseases: leg ulcers. BMJ. 1991;303776- 779
PubMedArticle
111.
Cullum  NNelson  EAFletcher  AWSheldon  TA Compression for venous leg ulcers. Cochrane Database Syst Rev. 2001;(2)CD000265
112.
Krasner  D Painful venous ulcers: themes and stories about their impact on quality of life. Ostomy Wound Manage. 1998;4438- 49
PubMed
113.
Smith  JJGuest  MGGreenhalgh  RMDavies  AH Measuring the quality of life in patients with venous ulcers. J Vasc Surg. 2000;31642- 649
PubMedArticle
114.
Ruckley  CV Socioeconomic impact of chronic venous insufficiency and leg ulcers. Angiology. 1997;4867- 69
PubMedArticle
115.
Diehm  CTrampisch  HJLange  SSchmidt  C Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet. 1996;347292- 294
PubMedArticle
116.
Pittler  MHErnst  E Horse-chestnut seed extract for chronic venous insufficiency: a criteria-based systematic review. Arch Dermatol. 1998;1341356- 1360
PubMedArticle
117.
Guyatt  GSchuñemann  HCook  DJaeschke  RPauker  SBucher  H Grades of recommendation for antithrombotic agents. Chest. 2001;119(1, suppl)3S- 7S
PubMedArticle
118.
Kahn  SRDucruet  TJohri  Mfor the Venous Thrombosis Outcomes (VETO) Study Investigators, Resource utilisation and loss of productivity during the 4 months following a diagnosis of deep venous thrombosis [abstract]. J Thromb Haemost. 2003;1(7, suppl 1)abstract 181.
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