Download PDF
Semin Thromb Hemost 2007; 33(8): 821-828
DOI: 10.1055/s-2007-1000371
© Thieme Medical Publishers

Thrombolysis for Pulmonary Embolism and Venous Thrombosis: Is It Worthwhile?

Renée A. Douma1 , Pieter W. Kamphuisen1
  • 1Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Further Information

Publication History

Publication Date:
04 January 2008 (online)

    Permissions and Reprints

ABSTRACT

Venous thromboembolism is a frequently occurring and potentially fatal disease characterized by short-term and long-term sequelae. Conventional treatment consists of heparin and vitamin K antagonists, but there is an ongoing controversy if more aggressive therapy, such as thrombolytic drugs, should be used in selected patients to achieve faster clot lysis in pursuit of better clinical outcome. A review of the literature shows that thrombolytic therapy is not recommended in the treatment of venous thrombosis. Although in deep vein thrombosis systemically administered and catheter-directed thrombolysis both offer advantages in improving vein patency and reducing the postthrombotic syndrome (PTS), prevention of severe PTS remains unproved while the bleeding risk is high. In pulmonary embolism (PE), thrombolytic therapy is generally recommended for patients with massive PE and hemodynamic instability, despite scarce and inconclusive evidence. There is no evidence that thrombolysis has a benefit over standard anticoagulant treatment in normotensive patients with acute PE, but more research is needed to better identify the subgroup of patients with nonmassive PE in whom the risk-benefit ratio is most favorable. Until this group is defined and the benefit of thrombolytic therapy is demonstrated, thrombolytic therapy should only be considered in patients with signs of massive PE and hemodynamic shock.

KEYWORDS

Venous thromboembolism - pulmonary embolism - deep venous thrombosis - thrombolytic therapy - risk stratification

REFERENCES

  • 1 White RHCommentEndCommentBody . The epidemiology of venous thromboembolism.  Circulation. 2003;  107(Suppl 1) 4-8
    PubMedGoogle Scholar
  • 2 Kahn S R. Frequency and determinants of the postthrombotic syndrome after venous thromboembolism.  Curr Opin Pulm Med. 2006;  12 299-303
    CrossrefPubMedGoogle Scholar
  • 3 Lindner D J, Edwards J M, Phinney E S, Taylor Jr L M, Porter J M. Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis.  J Vasc Surg. 1986;  4 436-442
    CrossrefPubMedGoogle Scholar
  • 4 Buller H R, Cohen A T, Davidson B et al.. Idraparinux versus standard therapy for venous thromboembolic disease.  N Engl J Med. 2007;  357 1094-1104
    CrossrefPubMedGoogle Scholar
  • 5 Wells P S, Forster A J. Thrombolysis in deep vein thrombosis: is there still an indication?.  Thromb Haemost. 2001;  86 499-508
    PubMedGoogle Scholar
  • 6 Watson L I, Armon M P. Thrombolysis for acute deep vein thrombosis.  Cochrane Database Syst Rev. 2004;  4 CD002783
    PubMedGoogle Scholar
  • 7 Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial.  Eur J Vasc Endovasc Surg. 2002;  24 209-214
    CrossrefPubMedGoogle Scholar
  • 8 Mewissen M W, Seabrook G R, Meissner M H, Cynamon J, Labropoulos N, Haughton S H. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry.  Radiology. 1999;  211 39-49
    CrossrefPubMedGoogle Scholar
  • 9 Alesh I, Kayali F, Stein P D. Catheter-directed thrombolysis (intrathrombus injection) in treatment of deep venous thrombosis: a systematic review.  Catheter Cardiovasc Interv. 2007;  70 143-148
    PubMedGoogle Scholar
  • 10 Douketis J D, Kearon C, Bates S, Duku E K, Ginsberg J S. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.  JAMA. 1998;  279 458-462
    CrossrefPubMedGoogle Scholar
  • 11 Carson J L, Kelley M A, Duff A et al.. The clinical course of pulmonary embolism.  N Engl J Med. 1992;  326 1240-1245
    CrossrefPubMedGoogle Scholar
  • 12 Goldhaber S Z, 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
  • 13 Barritt D W, Jordan S C. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial.  Lancet. 1960;  1 1309-1312
    PubMedGoogle Scholar
  • 14 Dalla-Volta S, Palla A, Santolicandro A et al.. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2.  J Am Coll Cardiol. 1992;  20 520-526
    CrossrefPubMedGoogle Scholar
  • 15 Goldhaber S Z, Haire W D, Feldstein M L et al.. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion.  Lancet. 1993;  341 507-511
    CrossrefPubMedGoogle Scholar
  • 16 Verstraete M, Miller G A, Bounameaux H et al.. Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism.  Circulation. 1988;  77 353-360
    CrossrefPubMedGoogle Scholar
  • 17 Obermaier R, Kroger J C, Benz S et al.. Successful catheter-guided local thrombolysis in acute pulmonary embolism in the early postoperative period after pancreatic head resection. [In French].  Chirurg. 2002;  73 945-949
    CrossrefPubMedGoogle Scholar
  • 18 Kelly P, Carroll N, Grant C, Barrett C, Kocka V. Successful treatment of massive pulmonary embolism with prolonged catheter-directed thrombolysis.  Heart Vessels. 2006;  21 124-126
    CrossrefPubMedGoogle Scholar
  • 19 Task Force. on Pulmonary Embolism, European Society of Cardiology . Guidelines on diagnosis and management of acute pulmonary embolism.  Eur Heart J. 2000;  21 211301-211336
    PubMedGoogle Scholar
  • 20 Kasper W, Konstantinides S, Geibel A et al.. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry.  J Am Coll Cardiol. 1997;  30 1165-1171
    CrossrefPubMedGoogle Scholar
  • 21 Konstantinides S, Geibel A, Olschewski M et al.. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry.  Circulation. 1997;  96 882-888
    CrossrefPubMedGoogle Scholar
  • 22 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 2817-2822
    CrossrefPubMedGoogle Scholar
  • 23 Wan S, Quinlan D J, Agnelli G, Eikelboom J W. 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
  • 24 Dalen J E, Alpert J S, Hirsh J. Thrombolytic therapy for pulmonary embolism: is it effective? Is it safe? When is it indicated?.  Arch Intern Med. 1997;  157 2250-2556
    PubMedGoogle Scholar
  • 25 Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism.  Cochrane Database Syst Rev. 2006;  2 CD004437
    PubMedGoogle Scholar
  • 26 Buller H R, Agnelli G, Hull R D, Hyers T M, Prins M H, Raskob G E. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126(Suppl) 401S-428S
    CrossrefPubMedGoogle Scholar
  • 27 Serra-Prat M, Jovell A J, Aymerich M. Efficacy and safety of thrombolytic therapy in pulmonary embolism: meta-analysis of randomized controlled trials. [In Spanish].  Med Clin (Barc). 1999;  112 685-689
    PubMedGoogle Scholar
  • 28 Thabut G, Thabut D, Myers R P et al.. Thrombolytic therapy of pulmonary embolism: a meta-analysis.  J Am Coll Cardiol. 2002;  40 1660-1667
    CrossrefPubMedGoogle Scholar
  • 29 Agnelli G, Becattini C, Kirschstein T. Thrombolysis vs heparin in the treatment of pulmonary embolism: a clinical outcome-based meta-analysis.  Arch Intern Med. 2002;  162 2537-2541
    CrossrefPubMedGoogle Scholar
  • 30 Kucher N, Rossi E, De Rosa M, Goldhaber S Z. Massive pulmonary embolism.  Circulation. 2006;  113 577-582
    CrossrefPubMedGoogle Scholar
  • 31 Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.  N Engl J Med. 2002;  347 1143-1150
    CrossrefPubMedGoogle Scholar
  • 32 Kucher N, Rossi E, De Rosa M, Goldhaber S Z. Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher.  Arch Intern Med. 2005;  165 1777-1781
    CrossrefPubMedGoogle Scholar
  • 33 Gibson N S, Sohne M, Buller H R. Prognostic value of echocardiography and spiral computed tomography in patients with pulmonary embolism.  Curr Opin Pulm Med. 2005;  11 380-384
    CrossrefPubMedGoogle Scholar
  • 34 van der Meer R W, Pattynama P M, Van Strijen M J 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;  235 798-803
    CrossrefPubMedGoogle Scholar
  • 35 Schoepf U J, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber S Z. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism.  Circulation. 2004;  110 3276-3280
    CrossrefPubMedGoogle Scholar
  • 36 Sohne M, Ten Wolde M, Buller H R. Biomarkers in pulmonary embolism.  Curr Opin Cardiol. 2004;  19 558-562
    CrossrefPubMedGoogle Scholar
  • 37 Becattini C, Vedovati M C, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis.  Circulation. 2007;  116 427-433
    CrossrefPubMedGoogle Scholar
  • 38 Kruger S, Graf J, Merx M W et al.. Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism.  Am Heart J. 2004;  147 60-65
    CrossrefPubMedGoogle Scholar
  • 39 Binder L, Pieske B, Olschewski M et al.. N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism.  Circulation. 2005;  112 1573-1579
    CrossrefPubMedGoogle Scholar
  • 40 Kostrubiec M, Pruszczyk P, Bochowicz A et al.. Biomarker-based risk assessment model in acute pulmonary embolism.  Eur Heart J. 2005;  26 2166-2172
    CrossrefPubMedGoogle Scholar
  • 41 Pruszczyk P, Kostrubiec M, Bochowicz A et al.. N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism.  Eur Respir J. 2003;  22 649-653
    CrossrefPubMedGoogle Scholar
  • 42 Tulevski I I, Ten Wolde M, van Veldhuisen D J et al.. Combined utility of brain natriuretic peptide and cardiac troponin T may improve rapid triage and risk stratification in normotensive patients with pulmonary embolism.  Int J Cardiol. 2007;  116 161-166
    CrossrefPubMedGoogle Scholar
  • 43 Kucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess O M. Incremental prognostic value of troponin I and echocardiography in patients with acute pulmonary embolism.  Eur Heart J. 2003;  24 1651-1656
    CrossrefPubMedGoogle Scholar
  • 44 Scridon T, Scridon C, Skali H, Alvarez A, Goldhaber S Z, Solomon S D. Prognostic significance of troponin elevation and right ventricular enlargement in acute pulmonary embolism.  Am J Cardiol. 2005;  96 303-315
    CrossrefPubMedGoogle Scholar
  • 45 Konstantinides S. Thrombolysis in submassive pulmonary embolism? Yes.  J Thromb Haemost. 2003;  1 1127-1129
    CrossrefPubMedGoogle Scholar
  • 46 Goldhaber S Z. Thrombolytic therapy for patients with pulmonary embolism who are hemodynamically stable but have right ventricular dysfunction: pro.  Arch Intern Med. 2005;  165 2197-2199
    CrossrefPubMedGoogle Scholar
  • 47 Dalen J E. Thrombolysis in submassive pulmonary embolism? No.  J Thromb Haemost. 2003;  1 1130-1132
    CrossrefPubMedGoogle Scholar
  • 48 Thabut G, Logeart D. Thrombolysis for pulmonary embolism in patients with right ventricular dysfunction: con.  Arch Intern Med. 2005;  165 2200-2203
    CrossrefPubMedGoogle Scholar
  • 49 Ten Wolde M, Tulevski I I, Mulder J W et al.. Brain natriuretic peptide as a predictor of adverse outcome in patients with pulmonary embolism.  Circulation. 2003;  107 2082-2084
    CrossrefPubMedGoogle Scholar

Renée A DoumaM.D. 

Department of Vascular Medicine, F4-143, Academic Medical Center

Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Email: r.a.douma@amc.uva.nl