Anticoagulation in Venous Thromboembolism

Chapter

Abstract

Venous thromboembolism (VTE) is a highly prevalent and potentially dangerous condition. While anticoagulation is the mainstay of therapy, thrombolytic therapy may be utilized in the acute setting for select patients. In this chapter, we review the risk factors for development of VTE and the key decision-making considerations for treatment. We highlight the role of acute therapies, such as thrombolytics, as well as appropriate selection of oral anticoagulants. Key advantages and disadvantages of warfarin and the direct oral anticoagulants are summarized. We review key aspects for chronic anticoagulation management, including the use of formal anticoagulation clinics. Finally, we discuss approaches to VTE recurrence risk stratification and the selection of antithrombotic agents for secondary VTE prevention. Numerous tables and figures outline decision-making steps and provide summary data from pivotal randomized trials in VTE management.

Keywords

Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism Anticoagulation Thrombolysis Thrombosis Shared Decision-Making Thrombophilia 

References

  1. 1.
    Goldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol. 2010;56(1):1–7.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    The Surgeon General’s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Rockville (MD). 2008. https://www.ncbi.nlm.nih.gov/pubmed/20669525.
  3. 3.
    Writing Group M, Mozaffarian D, Benjamin EJ, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–360.CrossRefGoogle Scholar
  4. 4.
    Spyropoulos AC, Hurley JS, Ciesla GN, de Lissovoy G. Management of acute proximal deep vein thrombosis: pharmacoeconomic evaluation of outpatient treatment with enoxaparin vs inpatient treatment with unfractionated heparin. Chest. 2002;122(1):108–14.CrossRefGoogle Scholar
  5. 5.
    De Martino RR, Wallaert JB, Rossi AP, Zbehlik AJ, Suckow B, Walsh DB. A meta-analysis of anticoagulation for calf deep venous thrombosis. J Vasc Surg. 2012;56(1):228–37. e221; discussion 236-227.CrossRefGoogle Scholar
  6. 6.
    Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2014;123(12):1802–9.CrossRefGoogle Scholar
  7. 7.
    Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e419S–94S.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Brandjes DP, Heijboer H, Buller HR, de Rijk M, Jagt H, ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med. 1992;327(21):1485–9.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–52.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–510.CrossRefGoogle Scholar
  11. 11.
    Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287–97.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hokusai VTEI, Buller HR, Decousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406–15.CrossRefGoogle Scholar
  14. 14.
    Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315–52.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Streiff MB, Agnelli G, Connors JM, et al. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis. 2016;41(1):32–67.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Barnes GD, Kanthi Y, Froehlich JB. Venous thromboembolism: predicting recurrence and the need for extended anticoagulation. Vasc Med. 2015;20(2):143–52.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033–69, 3069a-3069k.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788–830.CrossRefPubMedGoogle Scholar
  19. 19.
    Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402–11.CrossRefPubMedGoogle Scholar
  20. 20.
    Bartel B. Systemic thrombolysis for acute pulmonary embolism. Hosp Pract. 2015;43(1):22–7.CrossRefGoogle Scholar
  21. 21.
    Wang C, Zhai Z, Yang Y, et al. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010;137(2):254–62.CrossRefPubMedGoogle Scholar
  22. 22.
    Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M, Investigators M. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” trial). Am J Cardiol. 2013;111(2):273–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Kucher N, Boekstegers P, Muller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479–86.CrossRefPubMedGoogle Scholar
  24. 24.
    Kahn SR, Comerota AJ, Cushman M, et al. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014;130(18):1636–61.CrossRefPubMedGoogle Scholar
  25. 25.
    Enden T, Haig Y, Klow NE, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012;379(9810):31–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Stein PD, Matta F, Keyes DC, Willyerd GL. Impact of vena cava filters on in-hospital case fatality rate from pulmonary embolism. Am J Med. 2012;125(5):478–84.CrossRefPubMedGoogle Scholar
  27. 27.
    Stein PD, Matta F, Sabra MJ. Case fatality rate with vena cava filters in hospitalized stable patients with cancer and pulmonary embolism. Am J Med. 2013;126(9):819–24.CrossRefPubMedGoogle Scholar
  28. 28.
    Stein PD, Matta F. Vena cava filters in unstable elderly patients with acute pulmonary embolism. Am J Med. 2014;127(3):222–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Group PS. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (prevention du Risque d’Embolie Pulmonaire par interruption cave) randomized study. Circulation. 2005;112(3):416–22.CrossRefGoogle Scholar
  30. 30.
    Mismetti P, Laporte S, Pellerin O, et al. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial. JAMA. 2015;313(16):1627–35.CrossRefGoogle Scholar
  31. 31.
    Weinberg I, Abtahian F, Debiasi R, et al. Effect of delayed inferior vena cava filter retrieval after early initiation of anticoagulation. Am J Cardiol. 2014;113(2):389–94.CrossRefGoogle Scholar
  32. 32.
    Kinney TB, Aryafar H, Ray Jr CE, et al. ACR Appropriateness Criteria radiologic management of inferior vena cava filters. Expert panel on interventional radiology. 2012. https://guidelines.gov/summaries/summary/43868. Accessed 1 Dec 2016.
  33. 33.
    Caplin DM, Nikolic B, Kalva SP, et al. Quality improvement guidelines for the performance of inferior vena cava filter placement for the prevention of pulmonary embolism. J Vasc Interv Radiol. 2011;22(11):1499–506.Google Scholar
  34. 34.
    Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7):764–72.CrossRefGoogle Scholar
  35. 35.
    Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86(4):304–14.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484–8.CrossRefGoogle Scholar
  37. 37.
    Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146–53.CrossRefGoogle Scholar
  38. 38.
    Lee AY, Kamphuisen PW, Meyer G, et al. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA. 2015;314(7):677–86.CrossRefGoogle Scholar
  39. 39.
    Posch F, Konigsbrugge O, Zielinski C, Pabinger I, Ay C. Treatment of venous thromboembolism in patients with cancer: a network meta-analysis comparing efficacy and safety of anticoagulants. Thromb Res. 2015;136(3):582–9.CrossRefGoogle Scholar
  40. 40.
    Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125(1):1–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362(9383):523–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A, Eichinger S. The risk of recurrent venous thromboembolism in men and women. N Engl J Med. 2004;350(25):2558–63.CrossRefPubMedGoogle Scholar
  43. 43.
    Kovacs MJ, Kahn SR, Wells PS, et al. Patients with a first symptomatic unprovoked deep vein thrombosis are at higher risk of recurrent venous thromboembolism than patients with a first unprovoked pulmonary embolism. J Thromb Haemost. 2010;8(9):1926–32.CrossRefPubMedGoogle Scholar
  44. 44.
    Streiff MB. Predicting the risk of recurrent venous thromboembolism (VTE). J Thromb Thrombolysis. 2015;39(3):353–66.CrossRefPubMedGoogle Scholar
  45. 45.
    Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ. 2008;179(5):417–26.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121(14):1630–6.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Tosetto A, Iorio A, Marcucci M, et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost. 2012;10(6):1019–25.CrossRefGoogle Scholar
  48. 48.
    Rodger MA, Scarvelis D, Kahn SR, et al. Long-term risk of venous thrombosis after stopping anticoagulants for a first unprovoked event: a multi-national cohort. Thromb Res. 2016;143:152–8.CrossRefGoogle Scholar
  49. 49.
    Marcucci M, Iorio A, Douketis JD, et al. Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna prediction model with pooled individual patient data. J Thromb Haemost. 2015;13:775–81.CrossRefGoogle Scholar
  50. 50.
    Ruiz-Gimenez N, Suarez C, Gonzalez R, et al. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE registry. Thromb Haemost. 2008;100(1):26–31.CrossRefPubMedGoogle Scholar
  51. 51.
    Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003;349(7):631–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003;348(15):1425–34.CrossRefPubMedGoogle Scholar
  53. 53.
    Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368(8):709–18.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699–708.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Weitz JI, Lensing WA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017;376:1211–22.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Carrier M, Rodger MA, Wells PS, Righini M, LEG G. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost. 2011;9(6):1119–25.CrossRefPubMedGoogle Scholar
  57. 57.
    Cosmi B, Legnani C, Cini M, Guazzaloca G, Palareti G. D-dimer and residual vein obstruction as risk factors for recurrence during and after anticoagulation withdrawal in patients with a first episode of provoked deep-vein thrombosis. Thromb Haemost. 2011;105(5):837–45.CrossRefPubMedGoogle Scholar
  58. 58.
    Kearon C, Spencer FA, O’Keeffe D, et al. D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study. Ann Intern Med. 2015;162(1):27–34.CrossRefPubMedGoogle Scholar
  59. 59.
    Timp JF, Lijfering WM, Flinterman LE, et al. Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost. 2015;13(10):1823–32.CrossRefPubMedGoogle Scholar
  60. 60.
    Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366(21):1959–67.CrossRefPubMedGoogle Scholar
  61. 61.
    Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367(21):1979–87.CrossRefPubMedGoogle Scholar
  62. 62.
    Chopra V, Anand S, Hickner A, et al. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet. 2013;382(9889):311–25.CrossRefPubMedGoogle Scholar
  63. 63.
    Chopra V, Ratz D, Kuhn L, Lopus T, Lee A, Krein S. Peripherally inserted central catheter-related deep vein thrombosis: contemporary patterns and predictors. J Thromb Haemost. 2014;12(6):847–54.CrossRefPubMedGoogle Scholar
  64. 64.
    Chopra V, Flanders SA, Saint S, et al. The Michigan appropriateness guide for intravenous catheters (MAGIC): results from a multispecialty panel using the RAND/UCLA appropriateness method. Ann Intern Med. 2015;163(6 Suppl):S1–40.CrossRefPubMedGoogle Scholar
  65. 65.
    Ageno W, Beyer-Westendorf J, Garcia DA, Lazo-Langner A, McBane RD, Paciaroni M. Guidance for the management of venous thrombosis in unusual sites. J Thromb Thrombolysis. 2016;41(1):129–43.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Dentali F, Gianni M, Crowther MA, Ageno W. Natural history of cerebral vein thrombosis: a systematic review. Blood. 2006;108(4):1129–34.CrossRefPubMedGoogle Scholar
  67. 67.
    Ageno W, Riva N, Schulman S, et al. Long-term clinical outcomes of splanchnic vein thrombosis: results of an international registry. JAMA Intern Med. 2015;175(9):1474–80.CrossRefPubMedGoogle Scholar
  68. 68.
    Group CVOS. Natural history and clinical management of central retinal vein occlusion. The central vein occlusion study group. Arch Ophthalmol. 1997;115(4):486–91.CrossRefGoogle Scholar
  69. 69.
    Decousus H, Quere I, Presles E, et al. Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study. Ann Intern Med. 2010;152(4):218–24.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Decousus H, Prandoni P, Mismetti P, et al. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. N Engl J Med. 2010;363(13):1222–32.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Amin AN, Varker H, Princic N, Lin J, Thompson S, Johnston S. Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med. 2012;7:231–8.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534–44.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Cardiovascular MedicineFrankel Cardiovascular Center at the University of MichiganAnn ArborUSA
  2. 2.Anticoagulation Service, Faculty Group Practice: Pharmacy Innovations and PartnershipsUniversity of MichiganAnn ArborUSA

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