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High Dose and Short-Term Streptokinase Infusion in Patients with Pulmonary Embolism: Prospective with Seven-Year Follow-Up Trial

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Abstract

Background: High dose and short-term streptokinase infusion has proved to improve survival among few patients with pulmonary embolism and cardiogenic shock, without increasing hemorrhagic complications. However its efficacy and safety in terms of long follow-up and in major number of patients requires to be established.

Methods: Patients with pulmonary embolism proved through high probability V/Q lung scan, suggestive echocardiogram, or deep venous thrombosis were enrolled. All were assigned to receive 1,500,000 IU in one-hour streptokinase infusion. The primary end point was efficacy and safety of streptokinase regimen in terms of pulmonary arterial hypertension, right ventricular dysfunction, perfusion abnormalities, recurrence, mortality and hemorrhagic complications. In long-term follow-up, we assessed functional class, recurrence, chronic pulmonary arterial hypertension, postthrombotic-syndrome and mortality.

Results: A total of 40 consecutive patients (47.3±15.3 years of age) with large or massive pulmonary embolism were enrolled. In 35 patients high dose and short-term streptokinase regimen reversed acute pulmonary arterial hypertension, clinical and echocardiographic evidence of right ventricular dysfunction and improved pulmonary perfusion without increasing hemorrhagic complications. In acute phase 5 patients died, necropsy study performed in 4 patients showed massive pulmonary embolism and right ventricular myocardial infarction, without significant coronary arterial obstruction. Risk factors for mortality and recurrence were: right ventricular global hypokinesis (p<0.0001), 6 hours or over between onset symptoms and streptokinase regimen (p=0.02), severe systolic pulmonary arterial hypertension (p=0.001) right ventricular hypokinesis (p=0.001), hypoxemia (p=0.02) and right ventricular acute myocardial infarction (p<0.0001). Right ventricular hypokinesis (p=0.02) was the only independent risk factor for recurrence. In a seven-year follow-up of the original 35 patients who survived in acute phase, 2 patients were lost and 33 are alive, in functional class I, without recurrence or chronic pulmonary arterial hypertension.

Conclusions: Our report indicates that among properly selected high-risk PE patients, short-term streptokinase infusion is effective and safe.

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References

  1. Hirsh J, Gale GS, McDonald IG, McCarthy RA, Pitt A. Streptokinase therapy in acute major pulmonary embolism: effectiveness and problems. Br Med J 1968;4:729-734.

    PubMed  Google Scholar 

  2. Miller AH, Suton GC, Kerr IH, Gibson R, Honey M. Comparison of streptokinase and heparin treatment of isolated acute massive pulmonary embolism. Br Med J 1971;2:681-684.

    Google Scholar 

  3. Goldhaber SZ, Vaughan DE, Markis JE, Selwyn AP, Meyerovitz MF, Loscalzo J, et al. Acute pulmonary embolism treated with tissue plasminogen activator. Lancet 1986;2:886-889.

    Article  PubMed  Google Scholar 

  4. Verstraete M, Miller GAH, Bounameux H, Charbonier B, Colle JP, Lecorf G, et al. Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism. Circulation 1988;77:353-360.

    Google Scholar 

  5. Goldhaber SZ, Kessler CM, Heit J, Markis J, Sharma GVRK, Dawley D, et al. Randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 1988;2:293-298.

    Article  PubMed  Google Scholar 

  6. Dalla-Volta S, Palla A, Santolicandro A, Giuntini C, Pengo V, Visioli O, 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.

    PubMed  Google Scholar 

  7. Meyer G, Sors H, Charbonier B, Kasper W, Bassand JP, Kerr JH, et al. Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter double-blind trial. J Am Coll Cardiol 1992;19:239-245.

    PubMed  Google Scholar 

  8. Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL, et al. Alteplase versus heparin in acute pulmonary embolism; randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993;341:507-511.

    Article  PubMed  Google Scholar 

  9. Menevau N, Schiele F, Vuillemenot A, Valette B, Grolier G, Bernard Y, et al. Streptokinase vs alteplase in massive pulmonary embolism. A randomized trial assessing right haemodynamics and pulmonary vascular obstruction. Eur Heart J 1997;18: 1141-1148.

    PubMed  Google Scholar 

  10. Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser K, Rauber K, 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.

    PubMed  Google Scholar 

  11. Goldhaber SZ. Thrombolysis for pulmonary embolism. Prog Cardiovasc Dis 1991;34:113-133.

    Article  Google Scholar 

  12. Goldhaber SZ, Kessler CM, Heit JA, Elliot CG, Friedenberg WR, Heiselman DE, et al. Recombinant tissue-type plasminogen activator versus a novel High Dose and Short-Term Streptokinase Infusion 245 dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. J Am Coll Cardiol 1992;20:24-30.

    Google Scholar 

  13. Goldhaber SZ, Agnelli G, Levine MN. Reduced dose bolus alteplase vs conventional alteplase infusion for pulmonary embolism thromboembolism in massive pulmonary embolism: an international multicenter randomized trial. Chest 1994;106:718-723.

    PubMed  Google Scholar 

  14. Sors H, Pacouret G, Azarian R, Meyer G, Charbonnier B, Simmoneau G. Hemodynamic effects of bolus vs 2-h infusion of alteplase in acute massive pulmonary embolism: a randomized controlled multicenter trial. Chest 1994;106:712-717.

    PubMed  Google Scholar 

  15. Meneveau N, Schiele F, Metz D, Valette B, Attali P, Vuillemenot A, et al. Comparative efficacy of a twohour 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;31:1057-1063.

    Article  PubMed  Google Scholar 

  16. Goldhaber SZ. Thrombolysis in pulmonary embolism: a debatable indication. Thromb Haemost 2001;86: 444-451.

    PubMed  Google Scholar 

  17. Jerjes-Sanchez C, Ramirez-Rivera A, Garcia MM, Arriaga-Nava R, Valencia S, Rosado-Buzzo A, et al. Streptokinase and heparin versus heparin alone in massive pulmonary embolism: A randomized controlled trial. J Thromb Thrombolysis 1995;2: 227-229.

    PubMed  Google Scholar 

  18. Taks Force on Pulmonary Embolism, European Society of Cardiology. Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J 2000;21:1301-1334.

    Google Scholar 

  19. Tebbe U, Graf A, Kamke W, Zahn R, Forycki F, Kratzsch G, Günther B. Hemodynamic effects of double-bolus reteplase versus alteplase infusion in massive pulmonary embolism. Am Heart J 1999;138:39-44.

    PubMed  Google Scholar 

  20. Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L. Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J 1997; 134:478-487.

    Google Scholar 

  21. Kasper W, Konstantinides S, Geibel A, Tiede N, Krause T, Just H. Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism. Heart 1997;77:346-349.

    PubMed  Google Scholar 

  22. Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD, 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.

    Article  PubMed  Google Scholar 

  23. For I.Co.P.E.R, 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.

    Article  PubMed  Google Scholar 

  24. Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G, 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.

    PubMed  Google Scholar 

  25. Adams III NJE, Siegel BA, Goldstein UA, Jaffe AS. Elevation of CK-MB following pulmonary embolism. A manifestation of occult right ventricular infarction. Chest 1992;101:1203-1206.

    PubMed  Google Scholar 

  26. Ramirez-Rivera A, Gutierrez-Fajardo P, Jerjes-Sanchez C, Hernandez-Chavez G. Acute right myocardial infarction without significant obstructive coronary lesions secondary to massive pulmonary embolism. Chest 1993;104:80S.

    Google Scholar 

  27. Lualdi JC, Goldhaber SZ. Right ventricular dysfunction after acute pulmonary embolism: pathophysiolgic factors, detection and therapeutic implications. Am Heart J 1995;130:1276-1282.

    Article  PubMed  Google Scholar 

  28. Jerjes-Sanchez C, Ramirez-Rivera A, Ibarra-Perez C. The Dressler syndrome after pulmonary embolism. Am J Cardiol 1996;78:343-345.

    Article  PubMed  Google Scholar 

  29. Mittal SR, Jain S, Maheshwari S. Pulmonary embolism with isolated right ventricular infarction. Indian Heart J 1996;48:704-706.

    PubMed  Google Scholar 

  30. Giannitsis E, Muller-Bardoff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, Katus HA. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation 2000;102:211-217.

    PubMed  Google Scholar 

  31. Arcasoy SM, Kreit JW. Thrombolytic therapy of pulmonary embolism. Chest 1999;115:1695-1707.

    Article  PubMed  Google Scholar 

  32. Mikkola KM, Patel SR, Parker JA, Grodstein F, Goldhaber SZ. Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis. Am Heart J 1997;134:69-72.

    PubMed  Google Scholar 

  33. Kanter DS, Mikkola KM, Patel SR, Parker JA, Goldhaber SZ. Thrombolytic therapy for pulmonary embolism. Chest 1997;111:1241-1245.

    PubMed  Google Scholar 

  34. Solomon SD. Echocardiography in pulmonary embolism. In: Nakano T, Goldhaber SZ, eds. Pulmonary Embolism. Tokyo: Springer-Verlag, 1999:67-79.

    Google Scholar 

  35. Wolfe MW, Lee RT, Feldstein ML, Parker JA, Come PC, Goldhaber SZ. Prognostic significance of right ventricular hypokinesis and perfusion lung scan defects in pulmonary embolism. Am Heart J 1994;127:1371-1374.

    Article  PubMed  Google Scholar 

  36. Miller RL, Das S, Anandaragadan T, Leibowitz DW, Alderson PO, Thomashow B, et al. Association between right ventricular function and perfusion abnormalities in hemodynamically stable patients with acute pulmonary embolism. Chest 1998;113: 665-6670.

    PubMed  Google Scholar 

  37. Nass N, McConnell MV, Goldhaber SZ, Chyu S, Solomon SD. Recovery of regional right ventricular function after thrombolysis for pulmonary embolism. Am J Cardiol 1999;804-806.

  38. Ribeiro A, Lindmarker P, Johnsson H, Juhlin-Dannfelt A, Jorfeldt L. Pulmonary embolism: one year follow-up with echocardiography Doppler and five-year survival analysis. Circulation 1999;99:1325-1330.

    PubMed  Google Scholar 

  39. Sharma GVRK, Folland ED, McIntyre KM, Sasahara AA. Long-term benefit of thrombolytic therapy in patients with pulmonary embolism. Vascular Med 2000;5:91-95.

    Article  Google Scholar 

  40. Jerjes-Sa´nchez C, Ibarra-Pe´rez C, Rami´rez-Rivera A, Padua GA, Gonzalez CVM. Dressler-like syndrome after pulmonary embolism and infarction. Chest 1987;92:115-117.

    PubMed  Google Scholar 

  41. Hamel E, Pacouret G, Vincentelli D, Forissier JF, Peycher P, Pottier JM, et al. Thrombolysis or heparin 246 Jerjes-Sanchez et al. therapy in massive pulmonary embolism with ventricular dilatation: results from a 128-patient monocenter registry. Chest 2001;120:120-125.

    Article  PubMed  Google Scholar 

  42. Goldhaber SZ. Pulmonary embolism thrombolysis improves survival in massive pulmonary embolism. J Thromb Thrombolysis 1995;2:59.

    Google Scholar 

  43. Kearon C. Initial treatment of venous thromboembolism. Thromb Haemost 1999;82:887-891.

    PubMed  Google Scholar 

  44. Goldhaber SZ. The current role of thrombolytic therapy for pulmonary embolism. Sem Vasc Surg 2000;13:217-220.

    Google Scholar 

  45. Goldhaber SZ. A contemporary approach to thrombolytic therapy for pulmonary embolism. Vascular Medicine 2000;5:115-123.

    Article  PubMed  Google Scholar 

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Jerjes-Sanchez, C., Ramirez-Rivera, A., Arriaga-Nava, R. et al. High Dose and Short-Term Streptokinase Infusion in Patients with Pulmonary Embolism: Prospective with Seven-Year Follow-Up Trial. J Thromb Thrombolysis 12, 237–247 (2001). https://doi.org/10.1023/A:1015227125177

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