Incidence and cost burden of post-thrombotic syndrome

  • Aneel A. Ashrani
  • John A. Heit


Post-thrombotic syndrome (PTS) is a long-term complication of deep-vein thrombosis (DVT), manifesting as swelling, pain, edema, venous ectasia, and skin induration of the affected limb. PTS has been estimated to affect 23–60% of individuals with DVT, frequently occurring within 2 years of the DVT episode. Symptomatic DVT, post-operative asymptomatic DVT, and recurrent DVT are all risk factors for the development of PTS. Treatment of PTS is often ineffective and treatment-related costs represent a healthcare burden. Therefore, prevention of DVT is essential to reduce PTS, and thus improve outcomes and reduce overall healthcare costs. Although recommended by guidelines, appropriate DVT prophylaxis remains considerably underused. This review evaluates the incidence, risk factors, and economic impact of PTS. Increasing the awareness of PTS, and the methods to prevent this complication may help reduce its incidence, improve long-term outcomes in patients, and decrease resulting costs associated with treatment.


Anticoagulant therapy Deep-vein thrombosis Post-thrombotic syndrome Venous leg ulcers 



The authors received editorial support in the preparation of this manuscript, funded by sanofi-aventis, NJ, USA. The authors are fully responsible for content and editorial decisions for this manuscript.


  1. 1.
    Kahn SR, Solymoss S, Lamping DL et al (2000) Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality of life. J Gen Intern Med 15:425–429. doi: 10.1046/j.1525-1497.2000.06419.x CrossRefPubMedGoogle Scholar
  2. 2.
    Kahn SR, Hirsch A, Shrier I (2002) Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 162:1144–1148. doi: 10.1001/archinte.162.10.1144 CrossRefPubMedGoogle Scholar
  3. 3.
    Kahn SR, M’Lan CE, Lamping DL et al (2004) The influence of venous thromboembolism on quality of life and severity of chronic venous disease. J Thromb Haemost 2:2146–2151. doi: 10.1111/j.1538-7836.2004.00957.x CrossRefPubMedGoogle Scholar
  4. 4.
    Heit JA, Rooke TW, Silverstein MD, Mohr DN et al (2001) Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg 33:1022–1027. doi: 10.1067/mva.2001.113308 CrossRefPubMedGoogle Scholar
  5. 5.
    Prandoni P, Lensing AW, Cogo A et al (1996) The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 125:1–7PubMedGoogle Scholar
  6. 6.
    Prandoni P, Lensing AW, Prins MH et al (2004) Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med 141:249–256PubMedGoogle Scholar
  7. 7.
    Brandjes DP, Büller HR, Heijboer H et al (1997) Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 349:759–762. doi: 10.1016/S0140-6736(96)12215-7 CrossRefPubMedGoogle Scholar
  8. 8.
    Franzeck UK, Schalch I, Jäger KA et al (1996) Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zürich study). Circulation 93:74–79PubMedGoogle Scholar
  9. 9.
    Stain M, Schönauer V, Minar E et al (2005) The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease. J Thromb Haemost 3:2671–2676. doi: 10.1111/j.1538-7836.2005.01648.x CrossRefPubMedGoogle Scholar
  10. 10.
    Mudge M, Leinster SJ, Hughes LE (1988) A prospective 10-year study of the post-thrombotic syndrome in a surgical population. Ann R Coll Surg Engl 70:249–252PubMedGoogle Scholar
  11. 11.
    Schulman S, Lindmarker P, Holmström M et al (2006) Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. J Thromb Haemost 4:734–742. doi: 10.1111/j.1538-7836.2006.01795.x CrossRefPubMedGoogle Scholar
  12. 12.
    Mohr DN, Silverstein MD, Heit JA et al (2000) The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc 75:1249–1256CrossRefPubMedGoogle Scholar
  13. 13.
    Bergan JJ, Schmid-Schonbein GW, Smith PD et al (2006) Chronic venous disease. N Engl J Med 355:488–498. doi: 10.1056/NEJMra055289 CrossRefPubMedGoogle Scholar
  14. 14.
    Kahn SR, Ginsberg JS (2002) The post-thrombotic syndrome: current knowledge, controversies, and directions for future research. Blood Rev 16:155–165. doi: 10.1016/S0268-960X(02)00008-5 CrossRefPubMedGoogle Scholar
  15. 15.
    Lynch TG, Dalsing MC, Ouriel K et al (1999) Developments in diagnosis and classification of venous disorders: non-invasive diagnosis. Cardiovasc Surg 7:160–178. doi: 10.1016/S0967-2109(98)00007-6 CrossRefPubMedGoogle Scholar
  16. 16.
    Nicolaides AN, Hussein MK, Szendro G et al (1993) The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 17:414–419. doi: 10.1067/mva.1993.37694 CrossRefPubMedGoogle Scholar
  17. 17.
    Payne SP, London NJ, Newland CJ et al (1996) Ambulatory venous pressure: correlation with skin condition and role in identifying surgically correctible disease. Eur J Vasc Endovasc Surg 11:195–200. doi: 10.1016/S1078-5884(96)80051-7 CrossRefPubMedGoogle Scholar
  18. 18.
    Welkie JF, Comerota AJ, Katz ML et al (1992) Hemodynamic deterioration in chronic venous disease. J Vasc Surg 16:733–740. doi: 10.1067/mva.1992.40619 CrossRefPubMedGoogle Scholar
  19. 19.
    LeSiege CJ, McKean SC, Persson AV (1992) Importance of valvular incompetence after acute deep venous thrombosis. J Cardiovasc Surg (Torino) 33:710–714Google Scholar
  20. 20.
    Markel A, Manzo RA, Bergelin RO et al (1992) Valvular reflux after deep vein thrombosis: incidence and time of occurrence. J Vasc Surg 15:377–382. doi: 10.1067/mva.1992.32970 CrossRefPubMedGoogle Scholar
  21. 21.
    Milne AA, Stonebridge PA, Bradbury AW et al (1994) Venous function and clinical outcome following deep vein thrombosis. Br J Surg 81:847–849. doi: 10.1002/bjs.1800810618 CrossRefPubMedGoogle Scholar
  22. 22.
    van Bemmelen PS, Bedford G, Beach K et al (1991) Status of the valves in the superficial and deep venous system in chronic venous disease. Surgery 109:730–734PubMedGoogle Scholar
  23. 23.
    Hopkins NF, Wolfe JH (1992) ABC of vascular diseases. Deep venous insufficiency and occlusion. BMJ 304:107–110CrossRefPubMedGoogle Scholar
  24. 24.
    Villalta S, Bagatella P, Piccioli A et al (1994) Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome. Haemostasis 24(Suppl 1):158aGoogle Scholar
  25. 25.
    Widmer L, Da Silva A, Madar G (1981) Varikosis und chronisch venose Insuffizienz [Varicosis and chronic venous insufficiency]. In: Widmer LK, Stähelin HB, Nissen C, da Silva A (eds) Venen-, Arterien-, Krankheiten, koronare Herzkrankheit bei Berufstatigen. Easier Srudie. Verlag Hans Huber, Bern, pp 1–111Google Scholar
  26. 26.
    Ginsberg JS, Turkstra F, Buller HR et al (2000) Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study. Arch Intern Med 160:669–672. doi: 10.1001/archinte.160.5.669 CrossRefPubMedGoogle Scholar
  27. 27.
    Porter JM, Moneta GL (1995) Reporting standards in venous disease: an update. International Consensus Committee on chronic venous disease. J Vasc Surg 21:635–645. doi: 10.1016/S0741-5214(95)70195-8 CrossRefPubMedGoogle Scholar
  28. 28.
    Rutherford RB, Padberg FT Jr, Comerota AJ et al (2000) Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg 31:1307–1312. doi: 10.1016/S0741-5214(00)90143-5 CrossRefPubMedGoogle Scholar
  29. 29.
    Kahn SR, Desmarais S, Ducruet T et al (2006) Comparison of the Villalta and Ginsberg clinical scales to diagnose the post-thrombotic syndrome: correlation with patient-reported disease burden and venous valvular reflux. J Thromb Haemost 4:907–908. doi: 10.1111/j.1538-7836.2006.01824.x CrossRefPubMedGoogle Scholar
  30. 30.
    Kolbach DN, Neumann HA, Prins MH (2005) Definition of the post-thrombotic syndrome, differences between existing classifications. Eur J Vasc Endovasc Surg 30:404–414. doi: 10.1016/j.ejvs.2005.06.006 CrossRefPubMedGoogle Scholar
  31. 31.
    Bernardi E, Prandoni P (2000) The post-thrombotic syndrome. Curr Opin Pulm Med 6:335–342. doi: 10.1097/00063198-200007000-00015 CrossRefPubMedGoogle Scholar
  32. 32.
    Kahn SR, Shbaklo H, Lamping DL et al (2008) Determinants of health-related quality of life during the 2 years following deep venous thrombosis. J Thromb Haemost 6:1105–1112. doi: 10.1111/j.1538-7836.2008.03002.x CrossRefPubMedGoogle Scholar
  33. 33.
    Ginsberg JS, Hirsh J, Julian J et al (2001) Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med 161:2105–2109. doi: 10.1001/archinte.161.17.2105 CrossRefPubMedGoogle Scholar
  34. 34.
    Wille-Jørgensen P, Jørgensen T, Andersen M et al (1991) Postphlebitic syndrome and general surgery: an epidemiologic investigation. Angiology 42:397–403. doi: 10.1177/000331979104200507 CrossRefPubMedGoogle Scholar
  35. 35.
    Asbeutah AM, Riha AZ, Cameron JD et al (2004) Five-year outcome study of deep vein thrombosis in the lower limbs. J Vasc Surg 40:1184–1189. doi: 10.1016/j.jvs.2004.10.025 CrossRefPubMedGoogle Scholar
  36. 36.
    Ashrani AA, Heit JA, Lahr BD et al (2006) Role of venous outflow obstruction and venous valvular incompetence as mechanisms for venous stasis syndrome following deep vein thrombosis: a population-based cohort study. Blood 108: Abstr. 1495Google Scholar
  37. 37.
    Wille-Jørgensen P, Jorgensen LN, Crawford M (2005) Asymptomatic postoperative deep vein thrombosis and the development of postthrombotic syndrome. A systematic review and meta-analysis. Thromb Haemost 93:236–241PubMedGoogle Scholar
  38. 38.
    Kahn SR, Kearon C, Julian JA et al (2005) Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis. J Thromb Haemost 3:718–723. doi: 10.1111/j.1538-7836.2005.01216.x CrossRefPubMedGoogle Scholar
  39. 39.
    van Dongen CJ, Prandoni P, Frulla M et al (2005) Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 3:939–942. doi: 10.1111/j.1538-7836.2005.01333.x CrossRefPubMedGoogle Scholar
  40. 40.
    Lindner DJ, Edwards JM, Phinney ES et al (1986) Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis. J Vasc Surg 4:436–442. doi: 10.1067/mva.1986.avs0040436 CrossRefPubMedGoogle Scholar
  41. 41.
    Monreal M, Martorell A, Callejas JM et al (1993) Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study. J Intern Med 233:233–238CrossRefPubMedGoogle Scholar
  42. 42.
    Johnson BF, Manzo RA, Bergelin RO et al (1996) The site of residual abnormalities in the leg veins in long-term follow-up after deep vein thrombosis and their relationship to the development of the post-thrombotic syndrome. Int Angiol 15:14–19PubMedGoogle Scholar
  43. 43.
    Prandoni P, Frulla M, Sartor D et al (2005) Vein abnormalities and the post-thrombotic syndrome. J Thromb Haemost 3:401–402. doi: 10.1111/j.1538-7836.2004.01106.x CrossRefPubMedGoogle Scholar
  44. 44.
    Roumen-Klappe EM, den Heijer M, Janssen MC et al (2005) The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study. Thromb Haemost 94:825–830PubMedGoogle Scholar
  45. 45.
    Kahn SR, Elman EA, Bornais C et al (2005) Post-thrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults. Thromb Haemost 93:499–502PubMedGoogle Scholar
  46. 46.
    Yamaki T, Nozaki M, Sakurai H et al (2007) High peak reflux velocity in the proximal deep veins is a strong predictor of advanced post-thrombotic sequelae. J Thromb Haemost 5:305–312. doi: 10.1111/j.1538-7836.2007.02345.x CrossRefPubMedGoogle Scholar
  47. 47.
    Nelzén O, Bergqvist D, Lindhagen A (1991) Leg ulcer etiology—a cross sectional population study. J Vasc Surg 14:557–564. doi: 10.1067/mva.1991.30144 CrossRefPubMedGoogle Scholar
  48. 48.
    Biguzzi E, Mozzi E, Alatri A et al (1998) The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors. Thromb Haemost 80:575–577PubMedGoogle Scholar
  49. 49.
    Scott TE, LaMorte WW, Gorin DR et al (1995) Risk factors for chronic venous insufficiency: a dual case-control study. J Vasc Surg 22:622–628. doi: 10.1016/S0741-5214(95)70050-1 CrossRefPubMedGoogle Scholar
  50. 50.
    Ageno W, Piantanida E, Dentali F et al (2003) Body mass index is associated with the development of the post-thrombotic syndrome. Thromb Haemost 89:305–309PubMedGoogle Scholar
  51. 51.
    Ashrani AA, Heit JA, Rooke TW et al (2007) Impact of venous thromboembolism, venous stasis syndrome, venous outflow obstruction and venous valvular incompetence on quality of life and activities of daily living: a population-based case-control study. Presented at XXIst congress of the international society on thrombosis and haemostasis, Geneva, 6–12 July 2007 P-S-574Google Scholar
  52. 52.
    Kahn SR, Lamping DL, Ducruet T et al (2006) VEINES-QOL/Sym questionnaire was a reliable and valid disease-specific quality of life measure for deep venous thrombosis. J Clin Epidemiol 59:1049–1056PubMedGoogle Scholar
  53. 53.
    Lamping DL, Schroter S, Kurz X et al (2003) 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 37:410–419. doi: 10.1067/mva.2003.152 CrossRefPubMedGoogle Scholar
  54. 54.
    Bergqvist D, Jendteg S, Johansen L et al (1997) 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 126:454–457PubMedGoogle Scholar
  55. 55.
    Caprini JA, Botteman MF, Stephens JM et al (2003) Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States. Value Health 6:59–74. doi: 10.1046/j.1524-4733.2003.00204.x CrossRefPubMedGoogle Scholar
  56. 56.
    MacDougall DA, Feliu AL, Boccuzzi SJ et al (2006) Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health Syst Pharm 63(20 Suppl 6):S5–S15. doi: 10.2146/ajhp060388 CrossRefPubMedGoogle Scholar
  57. 57.
    Ramacciotti E, Gomes M, de Aguiar ET et al (2006) A cost analysis of the treatment of patients with post-thrombotic syndrome in Brazil. Thromb Res 118:699–704. doi: 10.1016/j.thromres.2005.12.005 CrossRefPubMedGoogle Scholar
  58. 58.
    Olin JW, Beusterien KM, Childs MB et al (1999) Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med 4:1–7PubMedGoogle Scholar
  59. 59.
    Phillips T, Stanton B, Provan A et al (1994) A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. J Am Acad Dermatol 31:49–53CrossRefPubMedGoogle Scholar
  60. 60.
    Kearon C, Kahn SR, Agnelli G et al (2008) Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl):454S–545S. doi: 10.1378/chest.08-0658 CrossRefPubMedGoogle Scholar
  61. 61.
    Ginsberg JS, Magier D, Mackinnon B et al (1999) Intermittent compression units for severe post-phlebitic syndrome: a randomized crossover study. CMAJ 160:1303–1306PubMedGoogle Scholar
  62. 62.
    Ginsberg JS (2004) Routine stocking therapy after deep venous thrombosis: a clinical dilemma. Ann Intern Med 141:314–315PubMedGoogle Scholar
  63. 63.
    O’Donnell MJ, McRae S, Kahn SR et al (2008) Evaluation of a venous-return assist device to treat severe post-thrombotic syndrome (VENOPTS). A randomized controlled trial. Thromb Haemost 99:623–629PubMedGoogle Scholar
  64. 64.
    Barwell JR, Taylor M, Deacon J et al (2000) Surgical correction of isolated superficial venous reflux reduces long-term recurrence rate in chronic venous leg ulcers. Eur J Vasc Endovasc Surg 20:363–368PubMedGoogle Scholar
  65. 65.
    Zamboni P, Cisno C, Marchetti F et al (2003) Minimally invasive surgical management of primary venous ulcers vs. compression treatment: a randomized clinical trial. Eur J Vasc Endovasc Surg 25:313–318. doi: 10.1053/ejvs.2002.1871 CrossRefPubMedGoogle Scholar
  66. 66.
    Barwell JR, Davies CE, Deacon J et al (2004) Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet 363:1854–1859. doi: 10.1016/S0140-6736(04)16353-8 CrossRefPubMedGoogle Scholar
  67. 67.
    Christenson JT (2007) Postthrombotic or non-postthrombotic severe venous insufficiency: impact of removal of superficial venous reflux with or without subcutaneous fasciotomy. J Vasc Surg 46:316–321. doi: 10.1016/j.jvs.2007.03.046 CrossRefPubMedGoogle Scholar
  68. 68.
    Falanga V (1998) Apligraf treatment of venous ulcers and other chronic wounds. J Dermatol 25:812–817PubMedGoogle Scholar
  69. 69.
    Jaschke E, Zabernigg A, Gattringer C (1999) Recombinant human granulocyte-macrophage colony-stimulating factor applied locally in low doses enhances healing and prevents recurrence of chronic venous ulcers. Int J Dermatol 38:380–386. doi: 10.1046/j.1365-4362.1999.00665.x CrossRefPubMedGoogle Scholar
  70. 70.
    McGuckin M, Waterman R, Brooks J et al (2002) Validation of venous leg ulcer guidelines in the United States and United Kingdom. Am J Surg 183:132–137. doi: 10.1016/S0002-9610(01)00856-X CrossRefPubMedGoogle Scholar
  71. 71.
    Heit JA, Cohen AT, Anderson FA et al (2005) Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood 106: Abstr. 910, p 267aGoogle Scholar
  72. 72.
    Goldhaber SZ, Dunn K, MacDougall RC (2000) New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest 118:1680–1684. doi: 10.1378/chest.118.6.1680 CrossRefPubMedGoogle Scholar
  73. 73.
    Kakkos SK, Daskalopoulou SS, Daskalopoulos ME et al (2006) Review on the value of graduated elastic compression stockings after deep vein thrombosis. Thromb Haemost 96:441–445PubMedGoogle Scholar
  74. 74.
    Partsch H, Kaulich M, Mayer W (2004) Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. Int Angiol 23:206–212PubMedGoogle Scholar
  75. 75.
    Wells PS, Forster AJ (2001) Thrombolysis in deep vein thrombosis: is there still an indication? Thromb Haemost 86:499–508PubMedGoogle Scholar
  76. 76.
    Johansson E, Ericson K, Zetterquist S (1976) Streptokinase treatment of deep venous thrombosis of the lower extremity. Clinical, phlebographic and plethysmographic evaluation of early and late results. Acta Med Scand 199:89–94PubMedGoogle Scholar
  77. 77.
    Arnesen H, Heilo A, Jakobsen E et al (1978) A prospective study of streptokinase and heparin in the treatment of deep vein thrombosis. Acta Med Scand 203:457–463PubMedGoogle Scholar
  78. 78.
    Turpie AG, Levine MN, Hirsh J et al (1990) Tissue plasminogen activator rt-PA vs heparin in deep vein thrombosis. Results of a randomized trial. Chest 97(4 Suppl):172S–175S. doi: 10.1378/chest.97.4.172S CrossRefPubMedGoogle Scholar
  79. 79.
    Comerota AJ, Throm RC, Mathias SD et al (2000) Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life. J Vasc Surg 32:130–137. doi: 10.1067/mva.2000.105664 CrossRefPubMedGoogle Scholar
  80. 80.
    AbuRahma AF, Perkins SE, Wulu JT et al (2001) Iliofemoral deep vein thrombosis: conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. Ann Surg 233:752–760. doi: 10.1097/00000658-200106000-00004 CrossRefPubMedGoogle Scholar
  81. 81.
    Bjarnason H, Kruse JR, Asinger DA et al (1997) Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 8:405–418. doi: 10.1016/S1051-0443(97)70581-5 CrossRefPubMedGoogle Scholar
  82. 82.
    Elsharawy M, Elzayat E (2002) Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg 24:209–214. doi: 10.1053/ejvs.2002.1665 CrossRefPubMedGoogle Scholar
  83. 83.
    Mewissen MW, Seabrook GR, Meissner MH et al (1999) Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology 211:39–49PubMedGoogle Scholar
  84. 84.
    Geerts WH, Bergqvist D, Pineo GF et al (2008) Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl):381S–453S. doi: 10.1378/chest.08-0656 CrossRefPubMedGoogle Scholar
  85. 85.
    Hull RD, Pineo GF, Francis C et al (2000) Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators. Arch Intern Med 160:2199–2207. doi: 10.1001/archinte.160.14.2199 CrossRefPubMedGoogle Scholar
  86. 86.
    Fitzgerald RH Jr, Spiro TE, Trowbridge AA et al (2001) Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg Am 83-A:900–906PubMedGoogle Scholar
  87. 87.
    Kleber FX, Witt C, Vogel G et al (2003) Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am Heart J 145:614–621. doi: 10.1067/mhj.2003.189 CrossRefPubMedGoogle Scholar
  88. 88.
    Samama MM, Cohen AT, Darmon JY et al (1999) A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 341:793–800. doi: 10.1056/NEJM199909093411103 CrossRefPubMedGoogle Scholar
  89. 89.
    Leizorovicz A, Cohen AT, Turpie AG et al (2004) Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 110:874–879. doi: 10.1161/01.CIR.0000138928.83266.24 CrossRefPubMedGoogle Scholar
  90. 90.
    Mismetti P, Laporte-Simitsidis S et al (2000) Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 83:14–19PubMedGoogle Scholar
  91. 91.
    Mismetti P, Laporte S, Darmon JY et al (2001) Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 88:913–930. doi: 10.1046/j.0007-1323.2001.01800.x CrossRefPubMedGoogle Scholar
  92. 92.
    Mismetti P, Laporte S, Zufferey P et al (2004) Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis. J Thromb Haemost 2:1058–1070. doi: 10.1111/j.1538-7836.2004.00757.x CrossRefPubMedGoogle Scholar
  93. 93.
    Cohen AT, Davidson BL, Gallus AS et al (2006) Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 332:325–329. doi: 10.1136/bmj.38733.466748.7C CrossRefPubMedGoogle Scholar
  94. 94.
    Turpie AG, Bauer KA, Eriksson BI et al (2002) Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 162:1833–1840. doi: 10.1001/archinte.162.16.1833 CrossRefPubMedGoogle Scholar
  95. 95.
    Botteman MF, Caprini J, Stephens JM et al (2002) Results of an economic model to assess the cost-effectiveness of enoxaparin, a low-molecular-weight heparin, versus warfarin for the prophylaxis of deep vein thrombosis and associated long-term complications in total hip replacement surgery in the United States. Clin Ther 24:1960–1986. doi: 10.1016/S0149-2918(02)80091-1 CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Hematology, Department of Internal Medicine, Stabile 6-60Mayo ClinicRochesterUSA
  2. 2.Divisions of Cardiovascular Medicine and Hematology Research, Department of Internal MedicineMayo ClinicRochesterUSA

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