Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Thrombolytic (fibrinolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis

Victor F Tapson, MD
Section Editor
Jess Mandel, MD
Deputy Editors
Geraldine Finlay, MD
Susanna I Lee, MD, PhD


Thrombolytic agents activate plasminogen to form plasmin, resulting in the accelerated lysis of thrombi. As a result, thrombolytic agents have been used in a variety of thrombotic disorders including acute myocardial infarction, stroke, acute pulmonary embolism (PE), and deep vein thrombosis (DVT).

The indications, contraindications, adverse effects, and outcomes of thrombolytic therapy in acute PE and DVT are discussed here. In addition, the types of thrombolytic agents and regimens are reviewed. Alternative treatment modalities and anticoagulation for acute PE and DVT are discussed elsewhere. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults" and "Overview of the treatment of lower extremity deep vein thrombosis (DVT)" and "Venous thromboembolism: Initiation of anticoagulation (first 10 days)".)


Evidence from randomized and retrospective observational studies in patients with acute pulmonary embolism (PE) indicates that thrombolytic therapy leads to early hemodynamic improvement, but at a cost of increased major bleeding. The effect of thrombolytic therapy on mortality and the frequency of recurrent thromboembolism remain questionable. (See 'Outcomes' below.)

Typically, only patients in whom the diagnosis of acute PE has been confirmed should be considered for thrombolytic therapy because the adverse effects can be devastating. For each patient, the indications and potential benefits must be carefully weighed against the risk of adverse events, taking into consideration the patient's values and preferences. (See 'Indications' below.)

Indications — Persistent hypotension or shock (ie, a systolic blood pressure <90 mmHg or a decrease in the systolic blood pressure by ≥40 mmHg from baseline) due to acute PE is the only widely accepted indication for systemic thrombolysis [1]. In most cases, systemic thrombolytic therapy should be considered only after acute PE has been confirmed because the adverse effects of this therapy can be severe. Because a pulmonary arteriogram immediately precedes catheter-based therapy, PE can be confirmed at that time when this procedure is undertaken [2].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 29, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. 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:e419S.
  2. Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35:3033.
  3. Kabrhel C, Jaff MR, Channick RN, et al. A multidisciplinary pulmonary embolism response team. Chest 2013; 144:1738.
  4. Dudzinski DM, Piazza G. Multidisciplinary Pulmonary Embolism Response Teams. Circulation 2016; 133:98.
  5. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149:315.
  6. Dotter CT, Seamon AJ, Rosch J. Streptokinase and heparin in the treatment of acute pulmonary embolism. Vasc Surg 1979; 13:42.
  7. Jerjes-Sanchez C, Ramírez-Rivera A, de Lourdes García M, et al. Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial. J Thromb Thrombolysis 1995; 2:227.
  8. Ly B, Arnesen H, Eie H, Hol R. A controlled clinical trial of streptokinase and heparin in the treatment of major pulmonary embolism. Acta Med Scand 1978; 203:465.
  9. Tibbutt DA, Davies JA, Anderson JA, et al. Comparison by controlled clinical trial of streptokinase and heparin in treatment of life-threatening pulmonay embolism. Br Med J 1974; 1:343.
  10. Urokinase pulmonary embolism trial. Phase 1 results: a cooperative study. JAMA 1970; 214:2163.
  11. Wan S, Quinlan DJ, Agnelli G, Eikelboom JW. Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials. Circulation 2004; 110:744.
  12. Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21:1301.
  13. Dalen JE. The uncertain role of thrombolytic therapy in the treatment of pulmonary embolism. Arch Intern Med 2002; 162:2521.
  14. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 1998; 114:561S.
  15. Goldhaber SZ. Contemporary pulmonary embolism thrombolysis. Chest 1995; 107:45S.
  16. Goldhaber SZ. Modern treatment of pulmonary embolism. Eur Respir J Suppl 2002; 35:22s.
  17. Goldhaber SZ. Echocardiography in the management of pulmonary embolism. Ann Intern Med 2002; 136:691.
  18. Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311:2414.
  19. Koć M, Kostrubiec M, Elikowski W, et al. Outcome of patients with right heart thrombi: the Right Heart Thrombi European Registry. Eur Respir J 2016; 47:869.
  20. Barrios D, Chavant J, Jiménez D, et al. Treatment of Right Heart Thrombi Associated with Acute Pulmonary Embolism. Am J Med 2017; 130:588.
  21. Grifoni S, Olivotto I, Cecchini P, et al. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation 2000; 101:2817.
  22. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370:1402.
  23. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014; 129:479.
  24. Becattini C, Agnelli G, Salvi A, et al. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res 2010; 125:e82.
  25. Engelberger RP, Moschovitis A, Fahrni J, et al. Fixed low-dose ultrasound-assisted catheter-directed thrombolysis for intermediate and high-risk pulmonary embolism. Eur Heart J 2015; 36:597.
  26. Piazza G, Hohlfelder B, Jaff MR, et al. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism. The SEATTLE II Study. J Am Coll Cardiol Intv 2015; 8:1382.
  27. Kuo WT, Banerjee A, Kim PS, et al. Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry. Chest 2015; 148:667.
  28. Konstantinides SV, Vicaut E, Danays T, et al. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol 2017; 69:1536.
  29. Bailén MR, Cuadra JA, Aguayo De Hoyos E. Thrombolysis during cardiopulmonary resuscitation in fulminant pulmonary embolism: a review. Crit Care Med 2001; 29:2211.
  30. Kürkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med 2000; 160:1529.
  31. Sharifi M, Berger J, Beeston P, et al. Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the "PEAPETT" study). Am J Emerg Med 2016; 34:1963.
  32. Abu-Laban RB, Christenson JM, Innes GD, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med 2002; 346:1522.
  33. van der Meer RW, Pattynama PM, van Strijen MJ, et al. Right ventricular dysfunction and pulmonary obstruction index at helical CT: prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology 2005; 235:798.
  34. Papanikolaou J, Spathoulas K, Makris D, Zakynthinos E. Thrombolysis for Massive Pulmonary Embolism in a Patient with Hemorrhagic Shock. Am J Respir Crit Care Med 2016; 194:e15.
  35. Anderson HV, Willerson JT. Thrombolysis in acute myocardial infarction. N Engl J Med 1993; 329:703.
  36. van Zonneveld AJ, Veerman H, Pannekoek H. Autonomous functions of structural domains on human tissue-type plasminogen activator. Proc Natl Acad Sci U S A 1986; 83:4670.
  37. Kalyan NK, Lee SG, Wilhelm J, et al. Structure-function analysis with tissue-type plasminogen activator. Effect of deletion of NH2-terminal domains on its biochemical and biological properties. J Biol Chem 1988; 263:3971.
  38. Marder VJ, Sherry S. Thrombolytic therapy: current status (1). N Engl J Med 1988; 318:1512.
  39. Sharifi M, Bay C, Skrocki L, et al. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol 2013; 111:273.
  40. Levine M, Hirsh J, Weitz J, et al. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest 1990; 98:1473.
  41. Meneveau N, Schiele F, Metz D, et al. Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up. J Am Coll Cardiol 1998; 31:1057.
  42. Lavonas EJ, Drennan IR, Gabrielli A, et al. Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S501.
  43. Fengler BT, Brady WJ. Fibrinolytic therapy in pulmonary embolism: an evidence-based treatment algorithm. Am J Emerg Med 2009; 27:84.
  44. Leeper KV Jr, Popovich J Jr, Lesser BA, et al. Treatment of massive acute pulmonary embolism. The use of low doses of intrapulmonary arterial streptokinase combined with full doses of systemic heparin. Chest 1988; 93:234.
  45. Barberena J. Intraarterial infusion of urokinase in the treatment of acute pulmonary thromboembolism: preliminary observations. AJR Am J Roentgenol 1983; 140:883.
  46. Schwarz F, Stehr H, Zimmermann R, et al. Sustained improvement of pulmonary hemodynamics in patients at rest and during exercise after thrombolytic treatment of massive pulmonary embolism. Circulation 1985; 71:117.
  47. The UKEP study: multicentre clinical trial on two local regimens of urokinase in massive pulmonary embolism. The UKEP Study Research Group. Eur Heart J 1987; 8:2.
  48. Verstraete M, Miller GA, Bounameaux H, et al. Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism. Circulation 1988; 77:353.
  49. Cuculi F, Kobza R, Bergner M, Erne P. Usefulness of aspiration of pulmonary emboli and prolonged local thrombolysis to treat pulmonary embolism. Am J Cardiol 2012; 110:1841.
  50. Tapson VF, Gurbel PA, Witty LA, et al. Pharmacomechanical thrombolysis of experimental pulmonary emboli. Rapid low-dose intraembolic therapy. Chest 1994; 106:1558.
  51. Akin H, Al-Jubouri M, Assi Z, et al. Catheter-directed thrombolytic intervention is effective for patients with massive and submassive pulmonary embolism. Ann Vasc Surg 2014; 28:1589.
  52. McCabe JM, Huang PH, Riedl L, et al. Usefulness and safety of ultrasound-assisted catheter-directed thrombolysis for submassive pulmonary emboli. Am J Cardiol 2015; 115:821.
  53. Tapson VF, Jimenez D. Catheter-Based Approaches for the Treatment of Acute Pulmonary Embolism. Semin Respir Crit Care Med 2017; 38:73.
  54. Fiumara K, Kucher N, Fanikos J, Goldhaber SZ. Predictors of major hemorrhage following fibrinolysis for acute pulmonary embolism. Am J Cardiol 2006; 97:127.
  55. Meyer G, Gisselbrecht M, Diehl JL, et al. Incidence and predictors of major hemorrhagic complications from thrombolytic therapy in patients with massive pulmonary embolism. Am J Med 1998; 105:472.
  56. Sadiq I, Goldhaber SZ, Liu PY, et al. Risk factors for major bleeding in the SEATTLE II trial. Vasc Med 2017; 22:44.
  57. Gore JM. Prevention of severe neurologic events in the thrombolytic era. Chest 1992; 101:124S.
  58. Kanter DS, Mikkola KM, Patel SR, et al. Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors. Chest 1997; 111:1241.
  59. Konstantinides S, Tiede N, Geibel A, et al. Comparison of alteplase versus heparin for resolution of major pulmonary embolism. Am J Cardiol 1998; 82:966.
  60. Sharma GV, Burleson VA, Sasahara AA. Effect of thrombolytic therapy on pulmonary-capillary blood volume in patients with pulmonary embolism. N Engl J Med 1980; 303:842.
  61. Come PC. Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions. Chest 1992; 101:151S.
  62. Sharma GV, Folland ED, McIntyre KM, et al. Longterm hemodynamic benefit of thrombolytic therapy in pulmonary embolic disease (abstract). J Am Coll Cardiol 1990; 15:65A.
  63. Tsang TS, Califf RM, Stebbins AL, et al. Incidence and impact on outcome of streptokinase allergy in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA in Occluded Coronary Arteries. Am J Cardiol 1997; 79:1232.
  64. Squire IB, Lawley W, Fletcher S, et al. Humoral and cellular immune responses up to 7.5 years after administration of streptokinase for acute myocardial infarction. Eur Heart J 1999; 20:1245.
  65. Goldhaber SZ, Buring JE, Lipnick RJ, Hennekens CH. Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med 1984; 76:393.
  66. Rogers LQ, Lutcher CL. Streptokinase therapy for deep vein thrombosis: a comprehensive review of the English literature. Am J Med 1990; 88:389.
  67. O'Meara JJ 3rd, McNutt RA, Evans AT, et al. A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis. N Engl J Med 1994; 330:1864.
  68. Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev 2014; :CD002783.
  69. Enden T, Haig Y, Kløw 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; 379:31.
  70. Ghanima W, Kleven IW, Enden T, et al. Recurrent venous thrombosis, post-thrombotic syndrome and quality of life after catheter-directed thrombolysis in severe proximal deep vein thrombosis. J Thromb Haemost 2011; 9:1261.
  71. Bashir R, Zack CJ, Zhao H, et al. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone to treat lower-extremity proximal deep vein thrombosis. JAMA Intern Med 2014; 174:1494.
  72. Garcia MJ, Lookstein R, Malhotra R, et al. Endovascular Management of Deep Vein Thrombosis with Rheolytic Thrombectomy: Final Report of the Prospective Multicenter PEARL (Peripheral Use of AngioJet Rheolytic Thrombectomy with a Variety of Catheter Lengths) Registry. J Vasc Interv Radiol 2015; 26:777.
  73. Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis. http://www.clinicaltrials.gov/ct2/results?term=NCT00790335 (Accessed on July 07, 2009).
  74. Laiho MK, Oinonen A, Sugano N, et al. Preservation of venous valve function after catheter-directed and systemic thrombolysis for deep venous thrombosis. Eur J Vasc Endovasc Surg 2004; 28:391.
  75. Lee SH, Kim HK, Hwang JK, et al. Efficacy of Retrievable Inferior Vena Cava Filter Placement in the Prevention of Pulmonary Embolism during Catheter-Directed Thrombectomy for Proximal Lower-Extremity Deep Vein Thrombosis. Ann Vasc Surg 2016; 33:181.