Management of Pulmonary Embolism: 2010 State-of-the-Art Update

Vascular Disease

Opinion statement

The morbidity and mortality of venous thromboembolism remain underrecognized and underappreciated. Suspected pulmonary embolism should be risk stratified using a validated clinical risk prediction tool; intermediate to high clinical suspicion requires objective diagnostic testing to confirm or refute the diagnosis. Therapy with unfractionated heparin, low molecular weight heparin, or fondaparinux should be initiated while diagnostic testing is pursued. Conversion to vitamin K antagonists requires a minimum of 5 days’ overlap between the parenteral agent and the vitamin K antagonist. Anticoagulation should be continued for a minimum of 3 to 6 months. Longer or even indefinite therapy may be required with a persistent hypercoagulable state. In patients with cancer, low molecular weight heparin monotherapy for the initial 3 to 6 months is preferred. In stable patients with normal biomarkers and a normal echocardiogram, accelerated discharge and outpatient therapy may be considered. In patients with hemodynamic instability, systemic thrombolytic therapy, catheter-directed therapy, or surgical embolectomy may be considered. Cancer screening and/or thrombophilia testing should be pursued only if the findings will directly affect patient therapy or long-term care.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Monreal M, Ruiz J, Olazabal A, et al.: Deep venous thrombosis and the risk of pulmonary embolism: a systematic study. Chest 1992, 102:657–658.CrossRefGoogle Scholar
  2. 2.
    Borst-Krafek B, Fink AM, Lipp C, et al.: Proximal extent of pelvic vein thrombosis and its association with pulmonary embolism. J Vasc Surg 2003, 37:518–522.CrossRefPubMedGoogle Scholar
  3. 3.
    Ghaye B, Willems V, Nchimi A, et al.: Relationship between the extent of deep venous thrombosis and the extent of acute pulmonary embolism as assessed by CT angiography. Br J Radiol 2009, 82:198–203.CrossRefPubMedGoogle Scholar
  4. 4.
    Spencer FA, Emery C, Lessard D, et al.: The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med 2006, 21:722–727.CrossRefPubMedGoogle Scholar
  5. 5.
    Heit JA, Cohen AT, Anderson FA Jr: Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood 2005, 106:267A, Abst 910.Google Scholar
  6. 6.
    Silverstein MD, Heit JA, Mohr DN, et al.: Trends in the incidence of deep venous thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998, 158:585–593.CrossRefPubMedGoogle Scholar
  7. 7.
    Stein PD, Beemath A, Olson RE: Trends in the incidence of pulmonary embolism and deep venous thrombosis in hospitalized patients. Am J Cardiol 2005, 95:1525–1526.CrossRefPubMedGoogle Scholar
  8. 8.
    Goldhaber SZ, Visani L, De Rosa M: Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999, 353:1386–1389.CrossRefPubMedGoogle Scholar
  9. 9.
    Wells PS, Anderson DR, Rodger M, et al.: Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department using a simple clinical model and d-dimer. Ann Intern Med 2001, 135:98–107.PubMedGoogle Scholar
  10. 10.
    Le Gal G, Righini M, Roy PM, et al.: Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006, 144:165–171.PubMedGoogle Scholar
  11. 11.
    Stein PD, Woodard PK, Weg JG, et al.: Diagnostic pathways in acute pulmonary embolism: recommendations from the PIOPED II investigators. Am J Med 2006, 119:1048–1055.CrossRefPubMedGoogle Scholar
  12. 12.
    Barritt DW, Jordan SC: Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet 1960, 1:1309–1312.CrossRefPubMedGoogle Scholar
  13. 13.••
    Kearon C, Kahn SR, Agnelli G, et al.: Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:454S–545S.CrossRefPubMedGoogle Scholar
  14. 14.
    Aujesky D, Obrosky DS, Stone RA, et al.: Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005, 172:1041–1046.CrossRefPubMedGoogle Scholar
  15. 15.
    Aujesky D, Roy P, Le Manach CP, et al.: Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J 2006, 27:476–481.CrossRefPubMedGoogle Scholar
  16. 16.
    Kucher N, Goldhaber SZ: Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation 2003, 108:2191–2194.CrossRefPubMedGoogle Scholar
  17. 17.
    AlMahameed A, Carman TL: Outpatient management of stable acute pulmonary embolism: proposed accelerated pathway for risk stratification. Am J Med 2007, 120:S18–S25.CrossRefPubMedGoogle Scholar
  18. 18.
    Davies CW, Wimperis J, Green ES, et al.: Early discharge of patients with pulmonary embolism: a two-phase observational study. Eur Resp J 2007, 30:708–714.CrossRefGoogle Scholar
  19. 19.
    Donze J, Le Gal G, Fine MJ, et al.: Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism. Thromb Haemost 2008, 100:943–948.PubMedGoogle Scholar
  20. 20.•
    Varga EA, Kerlin BA, Wurster MW: Social and ethical controversies in thrombophilia testing and update in genetic risk factors for venous thromboembolism. Semin Thromb Hemost 2008, 34:549–561.CrossRefPubMedGoogle Scholar
  21. 21.
    Polite BN, Lamont EB: Are venous thromboembolic events associated with subsequent breast and colorectal carcinoma diagnoses in the elderly? A case-control study of Medicare beneficiaries. Cancer 2006, 106:923–930.CrossRefPubMedGoogle Scholar
  22. 22.
    Carrier M, Le Gal G, Wells PS, et al.: Systematic review: Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med 2008, 149:323–333.PubMedGoogle Scholar
  23. 23.
    Carlbom DJ, Davidson BL: Pulmonary embolism in the critically ill. Chest 2007, 132:313–324.CrossRefPubMedGoogle Scholar
  24. 24.
    Holbrook AM, Pereira JA, Labiris R, et al.: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005, 165:1095–1106.CrossRefPubMedGoogle Scholar
  25. 25.
    Büller H, Davidson B, Decousus H, et al.: Fondaparinux or enoxaparin for the initial treatment of symptomatic venous thrombosis. A randomized trial. Ann Intern Med 2004, 140:867–873.PubMedGoogle Scholar
  26. 26.
    Matisse Investigators: Subcutaneous fondaparinux in the initial treatment of pulmonary embolism. N Engl J Med 2003, 349:1695–1702.CrossRefGoogle Scholar
  27. 27.
    Quinlan D, McQuillan A, Eikelboom J: Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism. Ann Intern Med 2004, 140:175–183.PubMedGoogle Scholar
  28. 28.
    Linkins L, Choi P, Douketis J: Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism. A meta-analysis. Ann Intern Med 2003, 139:893–900.PubMedGoogle Scholar
  29. 29.•
    Hirsh J, Bauer KA, Donati MB, et al.: Parenteral anticoagulants. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:141S–159S. This is a comprehensive review of the available parenteral anticoagulants.CrossRefPubMedGoogle Scholar
  30. 30.
    Raschke RA, Reilly BM, Guidry JR, et al.: The weight-based heparin dosing nomogram compared with a standard care nomogram: a randomized, controlled trial. Ann Intern Med 1993, 119:874–881.PubMedGoogle Scholar
  31. 31.
    Kearon C, Ginsberg JS, Julian JA, et al.: Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 2006, 296:935–942.CrossRefPubMedGoogle Scholar
  32. 32.
    Warkentin TE, Mauerer BT, Aster RH: Heparin-induced thrombocytopenia associated with fondaparinux. N Engl J Med 2007, 356:2653–2655.CrossRefPubMedGoogle Scholar
  33. 33.•
    Ansell J, Hirsh J, Hylek E, et al.: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:160S–198S.CrossRefPubMedGoogle Scholar
  34. 34.
    Kovacs MJ, Rodger M, Anderson DR, et al.: Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial. Ann Intern Med 2003, 138:714–719.PubMedGoogle Scholar
  35. 35.
    Deitcher SR: Interpretation of the International Normalized Ratio in patients with liver disease. Lancet 2002, 359:47–48.CrossRefPubMedGoogle Scholar
  36. 36.
    Tripodi A, Breukink-Engbers WGW, van den Besselar AMHP: Oral anticoagulant monitoring by laboratory or near-patient testing: what a clinician should be aware of. Semin Vasc Med 2003, 3:243–254.CrossRefPubMedGoogle Scholar
  37. 37.
    Warkentin TE, Greinacher A, Koster A, et al.: Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:340S–380S.CrossRefPubMedGoogle Scholar
  38. 38.
    Lubenow N, Eichler P, Lietz T, et al.: Lepirudin in patients with heparin-induced thrombocytopenia: results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost 2005, 3:2428–2436.CrossRefPubMedGoogle Scholar
  39. 39.
    Lewis BE, Wallis DE, Leya F, et al.: Argatroban anticoagulation in patients with heparin induced thrombocytopenia. Arch Intern Med 2003, 163:1849–1856.CrossRefPubMedGoogle Scholar
  40. 40.•
    Kiser TH, Burch JC, Klem PM, et al.: Safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia. Pharmacotherapy 2008, 28:1115–1124.CrossRefPubMedGoogle Scholar
  41. 41.
    Tardy B, Venet C, Zeni F, et al.: Short term effect of recombinant tissue plasminogen activator in patients with hemodynamically stable acute pulmonary embolism: results of a meta-analysis involving 464 patients. Thromb Res 2009, 124:672–677.CrossRefPubMedGoogle Scholar
  42. 42.
    Wan S, Quinlan DL, Agnelli G, et al.: Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials. Circulation 2004, 110:744–749.CrossRefPubMedGoogle Scholar
  43. 43.•
    Todd JL, Tapson VF: Thrombolytic therapy for acute pulmonary embolism: a critical appraisal. Chest 2009, 135:1321–1329.CrossRefPubMedGoogle Scholar
  44. 44.
    Kline JA, Hernandez-Nino J, Jones AE: Tenecteplase to treat pulmonary embolism in the emergency department. J Thromb Thrombolysis 2007, 23:101–105.CrossRefPubMedGoogle Scholar
  45. 45.
    Tebbe U, Graf A, Kamke W, et al.: Hemodynamic effects of double bolus reteplase versus alteplase infusion in massive pulmonary embolism. Am Heart J 1999, 138:39–44.CrossRefPubMedGoogle Scholar
  46. 46.
    Tebbe U, Bramlage P, Graf A, et al.: Desmoteplase in acute massive pulmonary thromboembolism. Thromb Haemost 2009, 101:557–562.PubMedGoogle Scholar
  47. 47.
    Goldhaber SZ: Advanced treatment strategies for acute pulmonary embolism, including thrombolysis and embolectomy. J Thromb Haemost 2009, 7(Suppl 1):322–327.CrossRefPubMedGoogle Scholar
  48. 48.
    PREPIC Study Group: 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, 112:416–422.CrossRefGoogle Scholar
  49. 49.
    Hann CL, Streiff MB: The role of vena cava filters in the management of venous thromboembolism. Blood Rev 2005, 19:179–202.CrossRefPubMedGoogle Scholar
  50. 50.
    PREPIC 2: prevention of recurrent pulmonary embolism by vena cava interruption. Available at http://www.clinicaltrials.gov.
  51. 51.•
    Kuo WT, Gould MK, Louie JD, et al.: Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol 2009, 20:1431–1440.CrossRefPubMedGoogle Scholar
  52. 52.
    Goldhaber SZ: Percutaneous mechanical thrombectomy for acute pulmonary embolism. A double-edged sword. Chest 2009, 132:363–365.CrossRefGoogle Scholar
  53. 53.
    Leacche M, Unic D, Goldhaber SZ, et al.: Modern surgical treatment of massive pulmonary embolism: results in 47 consecutive patients after rapid diagnosis and aggressive surgical approach. J Thorac Cardiovasc Surg 2005, 129:1018–1023.CrossRefPubMedGoogle Scholar
  54. 54.
    Kadner A, Schmidli J, Schӧnhoff F, et al.: Excellent outcomes after surgical treatment of massive pulmonary embolism in critically ill patients. J Thorac Cardiovasc Surg 2008, 136:448–451.CrossRefPubMedGoogle Scholar
  55. 55.••
    Gómez-Outes A, Lecumberri R, Pozo C, et al.: New anticoagulants: focus on venous thromboembolism. Curr Vasc Pharmacol 2009, 7:309–329.CrossRefPubMedGoogle Scholar
  56. 56.
    Khoo CW, Tay KH, Shantsila E, et al.: New oral anticoagulants. Int J Clin Pract 2009, 63:630–641.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.University Hospitals Case Medical CenterClevelandUSA

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