Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

Franck Paganelli; Marie Christine Alessi; Pierre Morange; Jean Michel Maixent; Samuel Lévy; Irène Juhan Vague

doi:10.1055/s-0037-1614637

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 82(01): 104-108
DOI: 10.1055/s-0037-1614637

Rapid Communication

Schattauer GmbH

Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

Autoren

Franck Paganelli

¹From the Division of Cardiology, University of Marseille, School of Medicine, France
Marie Christine Alessi

²From the Department of Haematology, University of Marseille, School of Medicine, France
Pierre Morange

²From the Department of Haematology, University of Marseille, School of Medicine, France
Jean Michel Maixent

¹From the Division of Cardiology, University of Marseille, School of Medicine, France
Samuel Lévy

¹From the Division of Cardiology, University of Marseille, School of Medicine, France
Irène Juhan Vague

²From the Department of Haematology, University of Marseille, School of Medicine, France

Abstract

Summary

Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries.

Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance.

Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

Volltext

Referenzen

References
1 The GUSTO Angiographic Investigators The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-22.
2 Califf RM, Topol EJ, Georges BS, Boswick JM, Lee KL, Stump D, Dillon J, Abbotsmith C, Candela RJ, Kerciakes DJ, O’Neil WW, Stack RS. TAMI study group. Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: results of the Thrombolysis and angioplasty in Myocardial Infarction (TAMI) trial. Circulation 1988; 77: 1090-9.
3 Eisenberg P, Sherman L, Jaffe A. Paradox elevation of fibrinopeptide A after streptokinase: Evidence for continued thrombosis despite intense fibrinolysis. J Am Coll Cardiol 1987; 10: 527-9.
4 Owen J, Fiedman K, Grosman B, Wilkins C, Berke A, Powers E. Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity. Blood 1988; 72: 616-20.
5 Gulba DC, Barthel M, Westhoff-Bleck M, Jost S, Rafflenbeul W, Daniel WG, Hecker H, Lichtlen PR. Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy. Circulation 1991; 83: 937-44.
6 Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-7.
7 Vaughan DE, Declerck PJ, Van Houtte E, De Mol M, Collen D. Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo. Thromb Haemost 1992; 68: 60-5.
8 Marsh JJ, Konopka RG, Lang IM, Wang H, Pedersen C, Chiles P, Reilly CF, Moser KM. Suppression of thrombolysis in a canine model of pulmonary embolism. Circulation 1994; 90: 3091-7.
9 Biemond BJ, Levi M, Corinel R, Janse MJ, ten Cate JW, Pannekoek H. Thrombolysis and reocclusion in experimental jugular vein and coronary artery thrombosis. Effects of a plasminogen activator inhibitor type 1 neutralizing monoclonal antibody. Circulation 1995; 91: 1175-81.
10 Carmeliet P, Kieckens L, Schoonjans L, Ream B, van Nuffelen A, Prendergast G, Cole M, Bronson R, Collen D, Mulligan RC. Plasminogen activator inhibitor 1 gene deficient mice. J Clin Invest 1993; 92: 2746-55.
11 Friederich PW, Levi M, Biemond BJ, Charlton P, Templeton D, VanZonneveld AJ, Bevan P, Pannekoek H, Tencate JW. Novel low-molecular-weight inhibitor of PAI-1 (XR5118) promotes endogenous fibrinoly-sis and reduces post thrombolysis thrombus growth in rabbits. Circulation 1997; 96: 916-21.
12 Hamsten A, Wiman B, De Faire U, Blömback M. Increased levels of rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. Lancet 1987; i: 3-9.
13 Juhan-Vague I, Pyke SDM, Alessi MC, Jespersen J, Haverkate F, Thomp-son SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation 1996; 94: 2057-63.
14 Lucore CL, Sobel BE. Interaction of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications. Circulation 1988; 77: 660-9.
15 Munkvad S, Gram J, Jespersen J. Increase of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma after thrombolytic therapy of patients with myocardial infarction. A randomised, placebo controlled study. Fibrinolysis 1992; 6: 45-50.
16 Rapold H, Grimaudo V, Declerk PJ, Kruithof EKO, Bachmann F. Plasma levels of plasminogen activator inhibitor type 1, β-thromboglobulin, and fibrinopeptide A before, during and after treatment of acute myocardial infarction with alteplase. Blood 1991; 78: 1490-5.
17 Hirashima O, Ogawa H, Oshima S, Sakamoto T, Honda Y, Sakata S, Masuda T, Miyao Y, Yasue H. Serial changes of plasma plasminogen activator inhibitor activity in acute myocardial infarction: difference between thrombolytic therapy and direct coronary angioplasty. Am Heart J 1995; 130: 933-9.
18 Goto S, Kawai Y, Handa S, Abe S, Takahashi E, Watanabe K, Hori S, Ikeda Y. Serial changes in plasma concentration of plasminogen activator inhibitor-1 before and serially after thrombolytic therapy for acute myocardial infarction. Coronary care 1993; 82: 280-5.
19 Genser N, Lechleitner P, Maier J, Dienstl F, Artner-Dworzak E, Puschendorf B, Mair J. Rebound increase of plasminogen activatior inhibitor 1 after cessation of thrombolytic treatment for acute myocardial infarction is independent of type of plasminogen activator used. Clin Chem 1998; 44: 209-14.
20 Fujii S, Lucore CL, Hopkins WE, Billadello JJ, Sobel BE. Induction of synthesis of PAI-1 by tissue type plasminogen activator in human hepatic and endothelial cells. Thromb Haemost 1990; 64: 412-20.
21 Sane DC, Stump DC, Topol EJ, Sigmon KN, Kereiakes DJ, Georges BS, Mantell SJ, Macy E, Collen D, Califf RM. Correlation between baseline plasminogen activator inhibitor levels and clinical outcome during therapy with tissue plasminogen activator for acute myocardial infarction. Thromb Haemost 1991; 63: 275-9.
22 Barbash GI, Hod H, Roth A, Miller HI, Rath S, Zahav YH, Modan M, Zivelin A, Laniado S, Seligsohn U. Correlation of baseline plasminogen activator inhibitor activity with patency of the infarct related artery after thrombolytic therapy in acute myocardial infarction. Am J Cardiol 1989; 64: 1231-5.
23 Gray RP, Yudkin JS, Patterson DL. Enzymatic evidence of impaired reper-fusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: a role for plasminogen activator inhibitor. Br Heart J 1993; 70: 530-6.
24 Sakatomo T, Yasue H, Ogawa H, Misumi I, Masuda T. Association of patency of infarcted-related coronary artery with plasma levels of plasminogen activator inhibitor activity in acute myocardial infarction. Am J Cardiol 1992; 70: 271-6.
25 Schneiderman J, Sawdey MS, Keeton MR, Bordin GM, Bernstein EF, Dilley RB, Loskutoff DJ. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci USA 1992; 89: 6998-7002.
26 Chomiki N, Henri M, Alessi MC, Anfosso F, Juhan-Vague I. Plasminogen-activator inhibitor-1 expression in human liver and healthy or athero-sclerotic vessel walls. Thromb Haemost 1994; 72: 44-53.
27 Andreotti F, Roncaglioni MC, Hackett DR, Khan MI, Regan T, Haider AW, Davies GJ, Kluft C, Maseri A. Early coronary reperfusion blunts the pro-coagulant response of plasminogen activator inhibitor-1 and von Wille-brand factor in acute myocardial infarction. J Am Coll Cardiol 1990; 16: 1553-60.
28 Huber K, Beckmann R, Probst P, Rauscha F, Kaindl F, Binder BR. The role of plasminogen activator in failure of thrombolytic therapy with recombinant tissue plasminogen activator. Z Kardiol 1993; 82: 195-200.
29 Aillaud MF, Juhan-Vague I, Alessi MC, Marecal M, Vinson MF, Arnaud C, Vague P, Collen D. Increased PA Inhibitor levels in the postoperative period. No cause effect relation with increased cortisol. Thromb Haemost 1985; 54: 466-8.
30 Huber K, Rosc D, Resch I, Schuster E, Golgar DH, Kaindl F, Binder BR. Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary disease and acute myocardial infarction. Thromb Haemost 1988; 60: 372-6.
31 Panhaloo A, Mohamed-Ali V, Denver B, Goodrick S, Yudkin JS. The influence of acute phase reactants and proinsulin-like molecules on plasmi- nogen activator inhibitor-1 post myocardial infarction. Diabetic Med 1996; 13: S46 (Abstract).
32 Juhan-Vague I, Thompson SG, Jespersen J. Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. Arterioscler Thromb 1993; 13: 1865-73.
33 Simpson AJ, Booth NA, Moore NR, Bennett B. The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. Brit J Haematol 1990; 75: 543-8.
34 Hagood JS, Olman MA, Godoy JA, Rivera KE, Fuller GM. Regulation of type I plasminogen activator inhibitor by fibrin degradation products in rat lung fibroblasts. Blood 1996; 87: 3749-57.
35 Shi GY, Wang SJ, Chang BI, Tasi CF, Lin MT, Chang WC, Wing LYC, Jen CJ, Wu HL. Regulation of plasminogen activator inhibitor activity by plas-min in endothelial cells. Thromb Res 1996; 81: 75-84.
36 Pietila K, Hermens WT, Harmoinen A, Baardman T, Pasternack A, Topol EJ, Simoons ML. Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with myocardial infarction treated with alteplase and streptokinase. Am J Cardiol 1997; 80: 1075-7.
37 Ohtani A, Murakami J, Hiranowakimoto A. T686, a novel inhibitor of plasminogen activator inhibitor-1, inhibits thrombosis without impairment of hemostasis in rats. Eur J Pharmacol 1997; 330: 151-6.