Review

Thrombolysis in Acute Pulmonary Thromboembolism

Authors: Priyanka A. Vyas, MD, Anthony A. Donato, MD

Abstract

Acute pulmonary embolism (PE) is a common clinical condition with presentations that may vary from asymptomatic subsegmental emboli to massive vascular obstruction and shock with high risk of death. Identifying patients at highest risk for death is critical to select those who would benefit most from thrombolytic therapy. New and evolving clinical prediction models, serum tests, and imaging modalities are being used to improve our ability to identify potential thrombolytic candidates. We review the evolution of the present guidelines on the management of PE, specifically regarding the evolving role of thrombolytics; outcomes following thrombolytic therapy, including mortality, hemorrhage, hemodynamic improvement, and prevention of chronic thromboembolic pulmonary hypertension; and our strategy for risk stratification of pulmonary embolism.

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References

1. Anderson FA Jr, 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: 933–938.
 
2. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585–593.
 
3. White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (23 suppl 1): 14–18.
 
4. 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.
 
5. Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21: 1301–1336.
 
6. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008; 29: 2276–2315.
 
7. 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: 1788–1830.
 
8. 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–494S.
 
9. Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 2002; 121: 877–905.
 
10. Goldhaber SZ, Haire WD, Feldstein ML, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993; 341: 507–511.
 
11. de Groot MR, Oostdijk AH, Engelage AH, et al. Changes in perfusion scintigraphy in the first days of heparin therapy in patients with acute pulmonary embolism. Eur J Nucl Med 2000; 27: 1481–1486.
 
12. Parker JA, Markis JE, Palla A, et al. Pulmonary perfusion after rt-PA therapy for acute embolism: early improvement assessed with segmental perfusion scanning. Radiology 1988; 166: 441–445.
 
13. 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.
 
14. Daniels LB, Parker JA, Patel SR, et al. Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. Am J Cardiol 1997; 80: 184–188.
 
15. Wan S, Quinlan DJ, 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.
 
16. Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, et al. Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J 1997; 134: 479–487.
 
17. 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.
 
18. Konstantinides S, Geibel A, Heusel G, et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347: 1143–1150.
 
19. 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.
 
20. Nijkeuter M, Hovens MMC, Davidson BL, et al. Resolution of thromboemboli in patients View Full Text | PubMed | CrossRef
 
21. Kline JA, Steuerwald MT, Marchick MR, et al. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009; 136: 1202–1210.
 
22. Pengo V, Lensing AWA, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350: 2257–2264.
 
23. Dalen JE. Thrombolysis in submassive pulmonary embolism? No. J Thromb Haemost 2003; 1: 1130–1132.
 
24. Konstantinides S. Thrombolysis in submassive pulmonary embolism? Yes. J Thromb Haemost 2003; 1: 1127–1129.
 
25. Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995; 108: 978–981.
 
26. Sanchez O, Trinquart L, Caille V, et al. Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study. Am J Respir Crit Care Med 2010; 181: 168–173.
 
27. Otero R, Trujillo-Santos J, Cayuela A, et al. Haemodynamically unstable pulmonary embolism in the RIETE Registry: systolic blood pressure or shock index? Eur Respir J 2007; 30: 1111–1116.
 
28. 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.
 
29. Mikkola KM, Patel SR, Parker JA, et al. Attenuation over 24 hours of the efficacy of thrombolysis of pulmonary embolism among patients with cancer. Am Heart J 1997; 134: 603–607.
 
30. Maleux G, Marchal P, Palmers M, et al. Catheter-directed thrombolytic 2293–2300.
 
31. Liu CY, Jain V, Shields AF, et al. Efficacy and safety of reteplase for central venous catheter occlusion in patients with cancer. J Vasc Interv Radiol 2004; 15 (1 Pt 1): 39–44.
 
32. Aujesky D, Roy P-M, Guy M, et al. Prognostic value of D-dimer in patients with pulmonary embolism. Thromb Haemost 2006; 96: 478–482.
 
33. Bruinstroop E, van de Ree MA, Huisman MV. The use of D-dimer in specific clinical conditions: a narrative review. Eur J Intern Med 2009; 20: 441–446.
 
34. Lankeit M, Konstantinides S. Mortality risk assessment and the role of thrombolysis in pulmonary embolism. Crit Care Clin 2011; 27: 953–967.
 
35. Klok FA, Mos ICM, Huisman MV. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. Am J Respir Crit Care Med 2008; 178: 425–430.
 
36. Sanchez O, Trinquart L, Colombet I, et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J2008; 29: 1569–1577.
 
37. 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.
 
38. Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116: 427–433.
 
39. Geibel A, Zehender M, Kasper W, et al. Prognostic value of the ECG on admission in patients with acute major pulmonary embolism. Eur Respir J 2005; 25: 843–848.
 
40. Sanchez O, Planquette B, Meyer G. Update on acute pulmonary embolism. Eur Respir Rev2009; 18: 137–147.
 
41. Goldhaber SZ. Echocardiography in the management of pulmonary embolism. Ann Intern Med 2002; 136: 691–700.
 
42. ten Wolde M, Söhne M, Quak E, et al. Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism. Arch Intern Med 2004; 164: 1685–1689.
 
43. Kucher N, Rossi E, De Rosa M, et al. 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.
 
44. Frémont B, Pacouret G, Jacobi D, et al. Prognostic value of echocardiographic right/left ventricular end-diastolic diameter ratio in patients with acute pulmonary embolism: results from a monocenter registry of 1,416 patients. Chest 2008; 133: 358–362.
 
45. Kucher N, Wallmann D, Carone A, et al. Incremental prognostic value of troponin I and echocardiography in patients with acute pulmonary embolism. Eur Heart J 2003; 24: 1651–1656.
 
46. Schoepf UJ, Kucher N, Kipfmueller F, et al. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism. Circulation 2004; 110: 3276–3280.
 
47. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol 2004; 44: 671–719.
 
48. Kaczyñska A, Pelsers MMAL, Bochowicz A, et al. Plasma heart-type fatty acid binding protein is superior to troponin and myoglobin for rapid risk stratification in acute pulmonary embolism. Clin Chim Acta 2006; 371: 117–123.
 
49. 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: 254–262.