Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test

Josune Orbe; Maite Zudaire; Rosario Serrano; Isabel Coma-Canella; Sara Martínez de Sizarrondo; Jose A. Rodríguez; Jose A. Páramo

doi:10.1160/TH07-07-0443

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(02): 382-387
DOI: 10.1160/TH07-07-0443

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test

Josune Orbe

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

,

Maite Zudaire

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

,

Rosario Serrano

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

,

Isabel Coma-Canella

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

,

Sara Martínez de Sizarrondo

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

,

Jose A. Rodríguez

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

,

Jose A. Páramo

¹Atherosclerosis Research Laboratory, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain

› Author Affiliations

Abstract

Summary

Atherosclerosis is the most common pathophysiologic substrate of coronary artery disease (CAD).Whereas plaque progression and arterial remodeling are critical components in chronic CAD, intracoronary thrombosis over plaque disruption is causally related to acute CAD. It was the objective of this study to investigate the differences between prior acute CAD and chronic CAD by a simple global coagulation assay measuring thrombin generation. A cross-sectional study involving 15 healthy controls, 35 patients with chronic stable CAD, and 60 patients after an episode of acute myocardial infarction (AMI) was performed. Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). In each patient the lag phase, velocity index and peak thrombin were obtained from the thrombogram profile. Traditional cardiovascular risk factors were recorded, and the inflammatory markers, fibrinogen and hs-C-reactive protein were determined. Compared with stable CAD patients, showing normal thrombograms, those with previous AMI showed earlier lag phase (p<0.05) and significant increase of both the velocity index (p<0.001) and peak thrombin (p<0.05), indicating faster and higher thrombin generation in the AMI group. Differences in thrombin generation between stable and acute CAD patients remained significant (p<0.001) after adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia). In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value to monitor hypercoagulable/ vulnerable blood and/or guide therapy in CAD.

Keywords

Thrombin - acute myocardial infarction - coronary syndrome

Full Text

References

References
1 Mann KG, Brummel K, Butenas S. What is all that thrombin for?. J Thromb Haemost 2003; 1: 1504-1514.
2 Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood 2005; 106: 2605-2612.
3 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
4 Hemker HC, Al Dieri R, Béguin S. Thrombin generation assays: accruing clinical relevance. Curr Opin Hematol 2004; 11: 170-175.
5 Tripodi A, Martinelli I, Chantarangkul V. et al. The endogenous thrombin potential and the risk of venous thromboembolism. Thromb Res. 2007 Epub ahead of print.
6 Simioni P, Castoldi E, Lunghi B. et al. An underestimated combination of opposites resulting in enhanced thrombotic tendency. Blood 2005; 106: 2363-2365.
7 Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005; 111: 3481-3488.
8 Libby P. Atherosclerosis: Disease biology affecting the coronary vasculature. Am J Cardiol 2006; 98 Suppl 3Q-9Q.
9 Virmani R, Burke AP, Farb A. et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47 (Suppl. 08) C13-C18.
10 Naghavi M, Libby P, Falk E. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-1778.
11 Naghavi M, Falk E, Hecht HS. et al. SHAPE Task Force. From vulnerable plaque to vulnerable patient--Part III: Executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol 2006; 98 2A 2H-15H.
12 Karnicki K, Owen WG, Miller RS. et al. Factors contributing to individual propensity for arterial thrombosis. Arterioscler Thromb Vasc Biol 2002; 22: 1495-1499.
13 Thompson SG, Kienast J, Pyke SD. et al. Haemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332: 635-641.
14 Ardissino D, Merlini PA, Gamba G. et al. Thrombin activity and early outcome in unstable angina pectoris. Circulation 1996; 93: 1634-1639.
15 Lopez Y, Paloma MJ, Rifon J. et al. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res 1999; 93: 71-78.
16 Ardissino D, Merlini PA, Bauer KA. et al. Coagulation activation and long-term outcome in acute coronary syndromes. Blood 2003; 102: 2731-2735.
17 Kalaria VG, Zoreba W, Moss AJ. et al. Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction; the THROMBO Investigators. Am J Cardiol 2000; 85: 1401-1408.
18 Kavsak PA, MacRae AR, Lustig V. et al. The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction. Am Heart J 2006; 152: 118-125.
19 Hron G, Kollars M, Binder BR. et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. J Am Med Assoc 2006; 296: 397-402.
20 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-2652.
21 Brodin E, Borvik T, Sandset PM. et al. Coagulation activation in young survivors of myocardial infarction (MI)-a population-based case-control study. Thromb Haemost 2004; 92: 178-184.
22 Lowe GD, Rumley A, Sweetnam PM. et al. Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic heart disease in the Caerphilly study. Thromb Haemost 2001; 86: 822-827.
23 Morange PE, Bickel C, Nicaud V. et al. Athero-Gene Investigators. Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study. Arterioscler Thromb Vasc Biol 2006; 26: 2793-2799.
24 Merlini PA, Bauer KA, Oltrona L. et al. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90: 61-68.
25 Merlini PA, Ardissino D, Bauer KA. et al. Persistent thrombin generation during heparin therapy in patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol 1997; 17: 1325-1330.
26 Seljeflot I, Hurlen M, Arnesen H. Increased levels of soluble tissue factor during long-term treatment with warfarin in patients after an acute myocardial infarction. J Thromb Haemost 2004; 2: 726-730.
27 Morange PE, Blankenberg S, Alessi MC. et al. ATHEROGENE INVESTIGATORS. Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study. J Thromb Haemost 2007; 5: 475-482
28 Joop K, Berckmans RJ, Nieuwland R. et al. Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms. Thromb Haemost 2001; 85: 810-820.
29 Pereira J, Alfaro G, Goycoolea M. et al. Circulating platelet-derived microparticles in systemic lupus erythematosus. Association with increased thrombin generation and procoagulant state. Thromb Haemost 2006; 95: 94-99.
30 Lacroix R, Sabatier F, Mialhe A. et al. Activation of plasminogen into plasmin at the surface of endothelial microparticles: a mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro. Blood 2007; 110: 2432-2439.
31 Griffin JH, Fernandez JA, Deguchi H. Plasma lipoproteins, haemostasis and thrombosis. Thromb Haemost 2001; 86: 386-394.
32 Khot UN, Khot MB, Bajzer CT. et al. Prevalence of conventional risk factors in patients with coronary heart disease. J Am Med Assoc 2003; 290: 898-904.
33 Bhatt DL, Fox KA, Hacke W. et al. CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354: 1706-1717.
34 Eikelboom JW, Weitz JI, Budaj A. et al. Clopidogrel does not suppress blood markers of coagulation activation in aspirin-treated patients with non-ST elevation acute coronary syndromes. Eur Heart J 2002; 23: 1771-1779.
35 Mak KH, Lee LH, Wong A. et al. Thrombin generation and fibrinolytic activities among patients receiving reduced-dose alteplase plus abciximab or undergoing direct angioplasty plus abciximab for acute myocardial infarction. Am J Cardiol 2002; 89: 930-936.
36 Merlini PA, Repetto A, Andreoli AM. et al. Effect of abciximab on prothrombin activation and thrombin generation in patients with acute myocardial infarction also receiving reteplase. Am J Cardiol 2004; 93: 195-198.
37 Granger CB, Becker R, Tracy RP. et al. Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I Trial. GUSTO-I Haemostasis Substudy Group. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries. J Am Coll Cardiol 1998; 31: 497-505.
38 Kottke-Marchant K, Bahit MC, Granger CB. et al. Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTOIIb haemostasis substudy. Eur Heart J 2002; 23: 1202-1212.