Activation Markers of Coagulation and Fibrinolysis: Alterations and Predictive Value in Acute Coronary Syndromes

Hans Martin Hoffmeister; Wolfgang Heller; Ludger Seipel

doi:10.1055/s-0037-1615559

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(S 01): 76-79
DOI: 10.1055/s-0037-1615559

Commentaries

Schattauer GmbH

Activation Markers of Coagulation and Fibrinolysis: Alterations and Predictive Value in Acute Coronary Syndromes

Hans Martin Hoffmeister

¹From the Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Tübingen, Germany

,

Wolfgang Heller

¹From the Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Tübingen, Germany

,

Ludger Seipel

¹From the Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Tübingen, Germany

› Author Affiliations

Abstract

Summary

Several alterations of the coagulation, of the fibrinolysis and of inflammation are known in patients with acute coronary syndromes. To extent current knowledge of the pathopysiology and to optimize therapeutical strategies, the new molecular markers can be used in clinical studies. Furthermore, several studies were undertaken to assess the prognostic value of activation markers of these systems for patients with unstable angina pectoris and acute myocardial infarction with or without thrombolytic therapy. The majority of studies focussed on markers of thrombin activation, fibrinogen, fibrin degradation products and t-PA and its main inhibitor PAI-1. While there are stimulating results from larger studies, the value for prognosis for the individual patient still is limited by the overlap of patients with good versus a poor outcome.

Key words

Fibrinolysis - coagulation - inflammation - activation marker - acute coronary syndromes

Full Text

References

References
1 Marder VJ. What does the »dimer test« test?. Circulation 1990; 82: 1514-5.
2 Hoffmeister HM, Jur M, Wendel HP, Heller W, Seipel L. Alterations of the coagulation, the fibrinolytic and the kallikrein-kinin system in the acute and post-acute phase in patients with unstable angina pectoris. Circulation 1995; 91: 2520-7.
3 Hoffmeister HM, Ruf M, Wendel HP, Heller W, Seipel L. Streptokinase-induced activation of the kallikrein-kinin system and of the contact phase in patients with acute myocardial infarction. Cardiovasc Pharmacol 1998; 31: 764-72.
4 Hoffmeister HM, Szabo S, Kastner C, Beyer ME, Helber U, Kazmaier S, Wendel HP, Heller W, Seipel L. Thrombolytic therapy in acute myocardial infarction. Comparison of procoagulant effects of streptokinase and alte-plase regimens with focus on the kallikrein system and plasmin. Circulation 1998; 98: 2527-33.
5 Hoffmeister HM, Ruf M, Wendel HP, Heller W. Alterations of the kallikrein system in patients with acute myocardial syndromes in comparison with patients with stable angina pectoris. Pharm Pharmacol Lett 1993; 3 (Suppl) 72-4.
6 Miche E, Baller D, Gleichmann U, Mannebach H, Schmidt H, Prohaska W. Fibrinogen und Leukozytenzahl bei koronarer Herzkrankheit. Korrelation zum angiographischen und klinischen Schweregrad. Z Kardiol 1995; 84: 92-8.
7 Hoffmeister HM, Jur M, Heller W, Seipel L. Korrelation zwischen moleku-laren Schadigungsmarkern und der Gerinnung bei Patienten mit instabiler Angina pectoris. Z Kardiol 1997; 86: 68.
8 Hamm CW, Heeschen C, Goldmann B, Vahanian A, Adgey J, Miguel CM, Rutsch W, Berger J, Kootstra J, Simoons ML. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. N Engl J Med 1999; 340: 1623-9.
9 Merlini PA, Bauer KA, Oltrona L, Ardissino D, Cattaneo M, Belli C, Mannucci PM, Rosenberg RD. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90: 61-8.
10 Merlini PA, Bauer KA, Oltrona L, Ardissino D, Spinola A, Cattaneo M, Broccolino M, Mannucci PM, Rosenberg RD. Thrombin generation and activity during thrombolysis and concomitant heparin therapy in patients with acute myocardial infarction. J Am Coll Cardiol 1995; 25: 203-9.
11 Hoffmeister HM, Jur M, Heller W, Seipel L. Hyperkoagulabilitat bei akutem koronaren Syndrom: Beeinflussung durch eine PTCA als Akut-intervention. In: Heinle H, Schulte H, Kaffernik H. Arteriosklerose; Stuttgart: W. Kohlhammer; 1995: 141-5.
12 Hoffmeister HM, Jur M, Heller W, Seipel L. Lack of impact of angioplasty on the time course of elevated coagulation and fibrinolysis parameters in unstable angina pectoris. Fibrinolysis & Proteolysis 1997; 11: 221-7.
13 Gulba DC, Westhoff-Bleck M, Jost S, Rafflenbeul W, Daniel WG, Hecker H, Lichtlen PR. Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Circulation 1991; 83: 937-44.
14 Scharfstein J, Abendschein DR, Eisenberg PR, George D, Cannon CP, Becker RC, Sobel B, Cupples LA, Braunwald E. Usefulness of fibrinoge-nolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. Am J Cardiol 1996; 78: 503-10.
15 Rapold HJ, Kuemmerli H, Weiss M, Baur H, Haeberli A. Monitoring of fibrin generation during thrombolytic therapy in acute myocardial infarction with recombinant tissue-type plasminoge activator. Circulation 1989; 79: 980-9.
16 Hoffmeister HM, Jur M, Ruf-Lehmann M, Helber U, Heller W, Seipel L. Endothelial tissue-type plasminogen activator release in coronary heart disease. J Am Coll Cardiol 1998; 31: 547-51.
17 Munkvad S, Gram J, Jespersen J. A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction. Eur Heart J 1990; 11: 525-8.
18 Juhan Vague I, Pyke S, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation 1996; 94: 2057-63.
19 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de, Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
20 Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New Engl J Med 1997; 336: 973-9.
21 Zalewski A, Shi Y, Nardone D, Bravette B, Weinstock P, Fischmann D, Wilson P, Goldberg S, Levin DC, Bjornsson TD. Evidence for reduced fibrinolytic activity in unstable angina at rest. Circulation 1991; 83: 1685-91.
22 Moss AJ, Goldstein RE, Marder VJ, Sparks CE, Oakes D, Greenberg H, Weiss HJ, Zareba W, Brown MW, Liang Ch, Lichstein E, Little WC, Gillespie JA, Voorhees LV, Krone RJ, Bodenheimer MM, Hochman J, Dwyer EM, Arora R, Marcus FI, Watelet LF, Case RB. Thrombogenic factors and recurrent coronary events. Circulation 1999; 99: 2517-22.
23 Hoffmeister HM, Jur M, Ruf M, Heller W, Seipel L. Inhibitors of the hemostasis and related systems in patients with acute myocardial infarction or unstable angina pectoris. Fibrinolysis 1995; 9 (Suppl. I) 104-8.
24 Lucore CL, Sobel BE. Interactions of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications. Circulation 1988; 77: 660-9.
25 Yasuda M, Takeuchi K, Hiruma M, Iida H, Tahara A, Itagane H, Toda I, Akioka K, Teragaki M, Oku H, Kanayama Y, Takeda T, Kolb WP, Tamerius JD. The complement system in ischemic heart disease. Circulation 1990; 81: 156-63.
26 Vaziri ND, Kennedy SC, Kennedy D, Gonzales E. Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris. Am J Med 1992; 93: 651-7.
27 Entman ML, Ballantyne CM. Inflammation in acute coronary syndromes. Circulation 1993; 22: 800-3.
28 Agostoni A, Gardinali M, Frangi D, Cafaro C, Conciato L, Sponzilli C, Salvioni A, Cugno M, Cicardi M. Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. Circulation 1994; 90: 2666-70.
29 Jur M, Heller W, Hoffmeister HM, Seipel L. Komplementsystem, Kreatin-kinase und Leukozytenaktivierung bei Patienten mit instabiler Angina pectoris Symptomatik. In: Heinle H, Schulte HJ, Kaffarnik H. Arteriosklerose Stuttgart: W. Kohlhammer 1995; 351-4.
30 Neumann FJ, Marx N, Gawaz M, Brand K, Ott I, Rokitta C, Sticherling C, Meint C, May A, Schomig A. Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets. Circulation 1997; 95: 2387-94.
31 Helber U, Buttcher E, Beyer ME, Hoffmeister HM. Expression des Ad-häsionsmoleküls MAC-1 auf Granulozyten bei Patienten mit instabiler Angina pectoris. Relation zu (tPA. In: Heinle H, Schulte HJ, Siegel G. Adhäsionmoleküle, Zytokine und Apoptose bei der Gefäßumgestaltung Stuttgart: W. Kohlhammer 1997; 78-82.
32 Mazzone A, De Servi S, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, Bramucci E, Angoli L, Marsico F, Specchia G, Notario A. Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 1993; 358-63.
33 Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. oduction of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997; 349: 462-6.
34 Tracy RP, Lemaitre RN, Psaty BM. et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol. (in press).
35 Capron L. Chlamydia in coronary plaques – hidden culprit or harmless hobo?. Nature Med 1996; 2: 856-7.
36 Epstein SE, Speir E, Zhou YF, Guetta E, Leon M, Finkel T. The role of infection in restenosis and atherosclerosis: focus on cytomegalovirus. Lancet 1996; 348: 13-7.
37 Gupta S, Leatham EW. The relation between Chlamydia pneumoniae and atherosclerosis. Heart 1997; 77: 7-8.
38 Kol A, Sperti G, Shani J, SchulhoffN van de Greef W, Landini MP, La Placa M, Maseri A, Crea F. Cytomegalovirus replication is not cause of instability in unstable angina. Circulation 1995; 91: 1910-3.
39 Mendall MA, Goggin PM, Molineaux N, Levy J, Toosy T, Strachan D, Camm AJ, Northfield TC. Relation of Helicobacter pylori infection and coronary heart disease. Br Heart J 1994; 71: 437-9.
40 Whincup PH, Mendall MA, Perry IJ, Strachan DP, Walker M. Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. Heart 1996; 75: 568-72.
41 Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994; 331: 417-24.
42 Liuzzo G, Biasucci LM, Rebuzzi AG, Gallimore R, Caligiuri G, Lanza GA, Quaranta G, Monaco C, Pepys MB, Maseri A. Plasma protein acute-phase response in unstable angina is not induced by ischemic injury. Circulation 1996; 94: 2373-80.
43 Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. Circulation 1997; 96: 4204-10.
44 Morrow DA, Rifai N, Antman EM, Weiner DL, McCabe CH, Cannon CP, Braunwald E. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. J Am Coll Cardiol 1998; 31: 1460-5.