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Drugs & Aging

, Volume 25, Issue 12, pp 1049–1060 | Cite as

Current Issues in Thromboprophylaxis in the Elderly

  • Parminder S. Chaggar
  • Kevin S. Channer
Review Article

Abstract

The elderly are at particularly high risk for arterial and venous thromboembolism, both of which are associated with significant morbidity and mortality in this age group. However, this age group often receives inadequate thromboprophylaxis because of concerns about bleeding risk, which is often over-estimated, denying patients the benefit of proven antithrombotic regimens. Guidelines advocate active and comprehensive thromboprophylactic strategies across all age groups and recent studies have addressed age considerations in both arterial and venous embolic disorders. Pharmacological thromboprophylaxis has repeatedly been shown to have a favourable risk-benefit profile, including in elderly populations. The benefits of thromboprophylaxis have long been recognized in surgical patients and recent studies have confirmed the safety and efficacy of thromboprophylaxis in medical patients, with most trials having included elderly cohorts. Given the difficulties and inconvenience associated with use of current anticoagulants, new drugs are under development and whilst some have been associated with significant adverse effects, others have demonstrated low bleeding risks without the need for coagulation monitoring. Meanwhile, other new agents currently on the market, such as fondaparinux sodium, have gained license for use in orthopaedic and general surgery patients, although clinical experience with these agents in elderly populations is limited. This article discusses the latest developments and current opinions regarding thromboprophylaxis, with particular emphasis on its relevance to the elderly population.

Keywords

Atrial Fibrillation Warfarin Rivaroxaban Enoxaparin Sodium Dabigatran Etexilate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Weill-Engerer S, Meaume S, Lahlou A, et al. Risk factors for deep vein thrombosis in inpatients aged 65 and older: a case-control multicenter study. J Am Geriatr Soc 2004; 52: 1299–304PubMedCrossRefGoogle Scholar
  2. 2.
    Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995; 155: 469–73PubMedCrossRefGoogle Scholar
  3. 3.
    White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: 14–8CrossRefGoogle Scholar
  4. 4.
    Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham Study. Stroke 1996; 27: 1760–4PubMedCrossRefGoogle Scholar
  5. 5.
    Torn M, Bollen WL, van der Meer FJ, et al. Risks of oral anticoagulant therapy with increasing age. Arch Intern Med 2005; 165: 1527–32PubMedCrossRefGoogle Scholar
  6. 6.
    South A, Iveson E, Allgar V, et al. The under use of thromboprophylaxis in older medical in-patients: a regional audit. QJM 2007; 100: 685–9PubMedCrossRefGoogle Scholar
  7. 7.
    Bratzler DW, Raskob GE, Murray CK, et al. Underuse of venous thromboembolism prophylaxis for general surgery patients: physician practices in the community hospital setting. Arch Intern Med 1998; 158: 1909–12PubMedCrossRefGoogle Scholar
  8. 8.
    Smith NL, Psaty BM, Furberg CD, et al. Temporal trends in the use of anticoagulants among older adults with atrial fibrillation. Arch Intern Med 1999; 159: 1574–8PubMedCrossRefGoogle Scholar
  9. 9.
    White RH, McBurnie MA, Manolio T, et al. Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort. Am J Med 1999; 106: 165–71PubMedCrossRefGoogle Scholar
  10. 10.
    Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 338S–400SPubMedCrossRefGoogle Scholar
  11. 11.
    Spyropoulos AC, Jenkins P, Bornikova L. A disease management protocol for outpatient perioperative bridge therapy with enoxaparin in patients requiring temporary interruption of long-term oral anticoagulation. Pharmacotherapy 2004; 24: 649–58PubMedCrossRefGoogle Scholar
  12. 12.
    Hill J, Treasure T. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients having surgery: summary of NICE guidance. BMJ 2007; 334: 1053–4PubMedCrossRefGoogle Scholar
  13. 13.
    Anderson Jr FA, Wheeler HB, Goldberg 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; 151: 933–8PubMedCrossRefGoogle Scholar
  14. 14.
    Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809–15PubMedCrossRefGoogle Scholar
  15. 15.
    Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001; 119: 132S–75SPubMedCrossRefGoogle Scholar
  16. 16.
    White RH, Zhou H, Gage BF. Effect of age on the incidence of venous thromboembolism after major surgery. J Thromb Haemost 2004; 2: 1327–33PubMedCrossRefGoogle Scholar
  17. 17.
    Kniffin Jr WD, Baron JA, Barrett J, et al. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994; 154: 861–6PubMedCrossRefGoogle Scholar
  18. 18.
    Lawall H, Hoffmanns W, Hoffmanns P, et al. Prevalence of deep vein thrombosis (DVT) in non-surgical patients at hospital admission. Thromb Haemost 2007; 98: 765–70PubMedGoogle Scholar
  19. 19.
    Alikhan R, Cohen AT, Combe S, et al. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med 2004; 164: 963–8PubMedCrossRefGoogle Scholar
  20. 20.
    Bosson JL, Labarere J, Sevestre MA, et al. Deep vein thrombosis in elderly patients hospitalized in subacute care facilities: a multicenter cross-sectional study of risk factors, prophylaxis, and prevalence. Arch Intern Med 2003; 163: 2613–8PubMedCrossRefGoogle Scholar
  21. 21.
    Oger E, Bressollette L, Nonent M, et al. High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients. Thromb Haemost 2002; 88: 592–7PubMedGoogle Scholar
  22. 22.
    Heit JA, Silverstein MD, Mohr DN, et al. The epidemiology of venous thromboembolism in the community. Thromb Haemost 2001; 86: 452–63PubMedGoogle Scholar
  23. 23.
    National Institute for Health and Clinical Excellence. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery (Nice clinical guideline no. 46) [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/CG046NICEguideline.pdf [Accessed 2008 Oct 9]
  24. 24.
    Tapson VF, Decousus H, Pini M, et al. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 2007; 132: 936–45PubMedCrossRefGoogle Scholar
  25. 25.
    Kahn SR, Panju A, Geerts W, et al. Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res 2007; 119: 145–55PubMedCrossRefGoogle Scholar
  26. 26.
    Rashid ST, Thursz MR, Razvi NA, et al. Venous thromboprophylaxis in UK medical inpatients. J R Soc Med 2005; 98: 507–12PubMedCrossRefGoogle Scholar
  27. 27.
    Goldhaber SZ, Dunn K, MacDougall RC. 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 2000; 118: 1680–4PubMedCrossRefGoogle Scholar
  28. 28.
    Piazza G, Seddighzadeh A, Goldhaber SZ. Double trouble for 2,609 hospitalized medical patients who developed deep vein thrombosis: prophylaxis omitted more often and pulmonary embolism more frequent. Chest 2007; 132: 554–61PubMedCrossRefGoogle Scholar
  29. 29.
    Burns PJ, Wilsom RG, Cunningham C. Venous thromboembolism prophylaxis used by consultant general surgeons in Scotland. J R Coll Surg Edinb 2001; 46: 329–33PubMedGoogle Scholar
  30. 30.
    Labarere J, Bosson JL, Brion JP, et al. Validation of a clinical guideline on prevention of venous thromboembolism in medical inpatients: a before-and-after study with systematic ultrasound examination. J Intern Med 2004; 256: 338–48PubMedCrossRefGoogle Scholar
  31. 31.
    Tooher R, Middleton P, Pham C, et al. A systematic review of strategies to improve prophylaxis for venous thromboembolism in hospitals. Ann Surg 2005; 241: 397–415PubMedCrossRefGoogle Scholar
  32. 32.
    Sellier E, Labarere J, Bosson JL, et al. Effectiveness of a guideline for venous thromboembolism prophylaxis in elderly post-acute care patients: a multicenter study with systematic ultrasonographic examination. Arch Intern Med 2006; 166: 2065–71PubMedCrossRefGoogle Scholar
  33. 33.
    Kucher N, Koo S, Quiroz R, et al. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med 2005; 352: 969–77PubMedCrossRefGoogle Scholar
  34. 34.
    Dentali F, Douketis JD, Gianni M, et al. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146: 278–88PubMedGoogle Scholar
  35. 35.
    Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006; 332: 325–9PubMedCrossRefGoogle Scholar
  36. 36.
    Leizorovicz A, Cohen AT, Turpie AG, et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110: 874–9PubMedCrossRefGoogle Scholar
  37. 37.
    Samama MM, Cohen AT, Darmon JY, et al. 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 1999; 341: 793–800PubMedCrossRefGoogle Scholar
  38. 38.
    Sherman DG, Albers GW, Bladin C, et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet 2007; 369: 1347–55PubMedCrossRefGoogle Scholar
  39. 39.
    Kamphuisen PW, Agnelli G. What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke? Thromb Res 2007; 119: 265–74PubMedCrossRefGoogle Scholar
  40. 40.
    McGarry LJ, Stokes ME, Thompson D. Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients. Thromb J 2006; 4: 17PubMedCrossRefGoogle Scholar
  41. 41.
    Cohen AT, Turpie AG, Leizorovicz A, et al. Thromboprophylaxis with dalteparin in medical patients: which patients benefit? Vasc Med 2007; 12: 123–7PubMedCrossRefGoogle Scholar
  42. 42.
    Freedman KB, Brookenthal KR, Fitzgerald Jr RH, et al. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg Am 2000; 82-A: 929–38PubMedGoogle Scholar
  43. 43.
    Amaragiri SV, Lees TA. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev 2000; (3): CD001484Google Scholar
  44. 44.
    Handoll HH, Farrar MJ, McBirnie J, et al. Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures. Cochrane Database Syst Rev 2002; (4): CD000305Google Scholar
  45. 45.
    Kierkegaard A, Norgren L. Graduated compression stockings in the prevention of deep vein thrombosis in patients with acute myocardial infarction. Eur Heart J 1993; 14: 1365–8PubMedCrossRefGoogle Scholar
  46. 46.
    Muir KW, Watt A, Baxter G, et al. Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke. QJM 2000; 93: 359–64PubMedCrossRefGoogle Scholar
  47. 47.
    Mazzone C, Chiodo GF, Sandercock P, et al. Physical methods for preventing deep vein thrombosis in stroke. Cochrane Database Syst Rev 2004; (4): CD001922Google Scholar
  48. 48.
    Labarere J, Bosson JL, Sevestre MA, et al. Brief report: graduated compression stocking thromboprophylaxis for elderly inpatients: a propensity analysis. J Gen Intern Med 2006; 21: 1282–7PubMedCrossRefGoogle Scholar
  49. 49.
    Fitzmaurice DA, Murray E. Thromboprophylaxis for adults in hospital. BMJ 2007; 334: 1017–8PubMedCrossRefGoogle Scholar
  50. 50.
    Cayley Jr WE. Preventing deep vein thrombosis in hospital inpatients. BMJ 2007; 335: 147–51PubMedCrossRefGoogle Scholar
  51. 51.
    Agnelli G, Bergqvist D, Cohen AT, et al. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 2005; 92: 1212–20PubMedCrossRefGoogle Scholar
  52. 52.
    Brotman DJ, Jaffer AK, Hurbanek JG, et al. Warfarin prophylaxis and venous thromboembolism in the first 5 days following hip and knee arthroplasty. Thromb Haemost 2004; 92: 1012–7PubMedGoogle Scholar
  53. 53.
    Burnett RS, Clohisy JC, Wright RW, et al. Failure of the American College of Chest Physicians-1A protocol for Lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 2007; 22: 317–24PubMedCrossRefGoogle Scholar
  54. 54.
    González Della Valle A, Serota A, Sorriaux G, et al. Venous thromboembolism is rare with a multimodal prophylaxis protocol after total hip arthroplasty. Clin Orthop Relat Res 2006; 444: 146–53PubMedCrossRefGoogle Scholar
  55. 55.
    Dorr LD, Gendelman V, Maheshwari AV, et al. Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment. J Bone Joint Surg Am 2007; 89: 2648–57PubMedCrossRefGoogle Scholar
  56. 56.
    Beksac B, González Della Valle A, Anderson J, et al. Symptomatic thromboembolism after one-stage bilateral THA with a multimodal prophylaxis protocol. Clin Orthop Relat Res 2007; 463: 114–9PubMedGoogle Scholar
  57. 57.
    Vives MJ, Hozack WJ, Sharkey PF, et al. Fixed minidose versus-adjusted low-dose warfarin after total joint arthroplasty: a randomized prospective study. J Arthroplasty 2001; 16: 1030–7PubMedCrossRefGoogle Scholar
  58. 58.
    Bern MM, Bierbaum B, Wetzner S, et al. Very low dose warfarin as prophylaxis against ultrasound detected deep vein thrombosis following primary hip replacement. Am J Hematol 2002; 71: 69–74PubMedCrossRefGoogle Scholar
  59. 59.
    Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–8PubMedCrossRefGoogle Scholar
  60. 60.
    Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998; 82: 2N–9NPubMedCrossRefGoogle Scholar
  61. 61.
    Lamassa M, Di Carlo A, Pracucci G, et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project). Stroke 2001; 32: 392–8PubMedCrossRefGoogle Scholar
  62. 62.
    Ibrahim SA, Kwoh CK. Underutilization of oral anticoagulant therapy for stroke prevention in elderly patients with heart failure. Am Heart J 2000; 140: 219–20PubMedCrossRefGoogle Scholar
  63. 63.
    Gage BF, Boechler M, Doggette AL, et al. Adverse outcomes and predictors of underuse of antithrombotic therapy in Medicare beneficiaries with chronic atrial fibrillation. Stroke 2000; 31: 822–7PubMedCrossRefGoogle Scholar
  64. 64.
    Fang MC, Stafford RS, Ruskin JN, et al. National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. Arch Intern Med 2004; 164: 55–60PubMedCrossRefGoogle Scholar
  65. 65.
    Cohen N, Almoznino-Sarafian D, Alon I, et al. Warfarin for stroke prevention still underused in atrial fibrillation: patterns of omission. Stroke 2000; 31: 1217–22PubMedCrossRefGoogle Scholar
  66. 66.
    Bungard TJ, Ghali WA, Teo KK, et al. Why do patients with atrial fibrillation not receive warfarin? Arch Intern Med 2000; 160: 41–6PubMedCrossRefGoogle Scholar
  67. 67.
    Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689–96PubMedCrossRefGoogle Scholar
  68. 68.
    Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349: 1019–26PubMedCrossRefGoogle Scholar
  69. 69.
    Lip GY, Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Thromb Res 2006; 118: 321–33PubMedCrossRefGoogle Scholar
  70. 70.
    Fang MC, Go AS, Hylek EM, et al. Age and the risk of warfarin-associated hemorrhage: the Anticoagulation and Risk Factors in Atrial Fibrillation study. J Am Geriatr Soc 2006; 54: 1231–6PubMedCrossRefGoogle Scholar
  71. 71.
    Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857–67PubMedGoogle Scholar
  72. 72.
    Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903–12PubMedCrossRefGoogle Scholar
  73. 73.
    Rash A, Downes T, Portner R, et al. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007; 36: 151–6PubMedCrossRefGoogle Scholar
  74. 74.
    Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493–503PubMedCrossRefGoogle Scholar
  75. 75.
    Garcia D, Hylek E. Stroke prevention in elderly patients with atrial fibrillation. Lancet 2007; 370: 460–1PubMedCrossRefGoogle Scholar
  76. 76.
    National Institute for Health and Clinical Excellence. The management of atrial fibrillation [online]. Available from URL: http://www.nice.org.uk/CG36 [Accessed 2008 Sep 3]
  77. 77.
    Weitz JI. Emerging anticoagulants for the treatment of venous thromboembolism. Thromb Haemost 2006; 96: 274–84PubMedGoogle Scholar
  78. 78.
    Fisher WD, Eriksson BI, Bauer KA, et al. Rivaroxaban for thromboprophylaxis after orthopaedic surgery: pooled analysis of two studies. Thromb Haemost 2007; 97: 931–7PubMedGoogle Scholar
  79. 79.
    Ford GA, Choy AM, Deedwania P, et al. Direct thrombin inhibition and stroke prevention in elderly patients with atrial fibrillation: experience from the SPORTIF III and V Trials. Stroke 2007; 38: 2965–71PubMedCrossRefGoogle Scholar
  80. 80.
    Lee WM, Larrey D, Olsson R, et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf 2005; 28: 351–70PubMedCrossRefGoogle Scholar
  81. 81.
    Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91–9PubMedCrossRefGoogle Scholar
  82. 82.
    Wells PS, Forgie MA, Simms M, et al. The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism. Arch Intern Med 2003; 163: 917–20PubMedCrossRefGoogle Scholar
  83. 83.
    Visser LE, Penning-van Bees BJ, Kasbergen AA, et al. Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants. Thromb Haemost 2002; 88: 705–10PubMedGoogle Scholar
  84. 84.
    Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005; 165: 1095–106PubMedCrossRefGoogle Scholar
  85. 85.
    Zhan C, Correa-de-Araujo R, Bierman AS, et al. Suboptimal prescribing in elderly outpatients: potentially harmful drug-drug and drug-disease combinations. J Am Geriatr Soc 2005; 53: 262–7PubMedCrossRefGoogle Scholar
  86. 86.
    Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 287S–310SPubMedCrossRefGoogle Scholar
  87. 87.
    Gurwitz JH, Field TS, Avorn J, et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med 2000; 109: 87–94PubMedCrossRefGoogle Scholar
  88. 88.
    Fehrman-Ekholm I, Skeppholm L. Renal function in the elderly (>70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance. Scand J Urol Nephrol 2004; 38: 73–7PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Cardiothoracic Transplant CentreWythenshawe HospitalManchesterUK
  2. 2.Department of CardiologyRoyal Hallamshire HospitalSheffieldUK

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