Persistent enhanced platelet activation in patients with acute myocardial infarction and coronary microvascular obstruction: clinical implications

Cristina Aurigemma; Giancarla Scalone; Fabrizio Tomai; Luca Altamura; Giovanni De Persio; Alessandra Stazi; Gaetano A. Lanza; Filippo Crea

doi:10.1160/TH13-02-0166

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(01): 122-130
DOI: 10.1160/TH13-02-0166

Platelets and Blood Cells

Schattauer GmbH

Persistent enhanced platelet activation in patients with acute myocardial infarction and coronary microvascular obstruction: clinical implications

Authors

Cristina Aurigemma

¹Università Cattolica del Sacro Cuore, Roma, Italy
Giancarla Scalone

¹Università Cattolica del Sacro Cuore, Roma, Italy
Fabrizio Tomai

²Euopean Hospital e Aurelia Hospital, Roma, Italy
Luca Altamura

²Euopean Hospital e Aurelia Hospital, Roma, Italy
Giovanni De Persio

²Euopean Hospital e Aurelia Hospital, Roma, Italy
Alessandra Stazi

¹Università Cattolica del Sacro Cuore, Roma, Italy
Gaetano A. Lanza

¹Università Cattolica del Sacro Cuore, Roma, Italy
Filippo Crea

¹Università Cattolica del Sacro Cuore, Roma, Italy

Abstract

Summary

About 30% of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing recanalisation of the infarct-related coronary artery do not achieve valid myocardial reperfusion (no-reflow phenomenon or coronary microvascular obstruction [MVO]). The mechanisms of MVO are incompletely understood. In this study we investigated the role platelet activation in the pathogenesis of coronary MVO in STEMI patients. We enrolled 48 STEMI patients (age 56.2 ± 11 years; 31 men), treated by primary percutaneous coronary intervention (PCI) followed by double anti-platelet treatment, and 20 control patients with stable coronary artery disease (CAD) on single antiplatelet treatment (age 57.5 ± 6 years, 12 men). STEMI patients were divided into two groups: 35 patients with complete myocardial reperfusion (MR) and 13 patients with coronary MVO despite successful PCI. Platelet activation was assessed on admission and at one-month follow-up by measuring platelet receptor expression and monocyteplatelet aggregates (MPAs). Platelet receptor expression, platelet receptor conformational change for fibrinogen binding availability and MPA formation were increased in STEMI patients with MVO compared to both STEMI patients with MR and stable CAD patients, both on admission and at one-month follow-up (p<0.05 for all). Among STEMI patients, platelet activation is greater in those who display coronary MVO, compared to those with MR, after successful PCI, both on admission and one month after STEMI, suggesting that enhanced platelet activation might be involved in the pathogenesis of MVO. The persistence of enhanced platelet activation despite double classical anti-platelet therapy suggests that new anti-platelet strategies should be considered in patients with coronary MVO.

Keywords

Microvascular obstruction - platelet aggregation - monocyte-platelet aggregates - adenosine - primary PCI

Full Text

References

References
1 Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 2001; 22: 729-739
2 Niccoli G, Kharbanda RK, Crea F. et al. No-reflow: again prevention is better than treatment. Eur Heart J 2010; 31: 2449-2455.
3 Ito H, Tomooka T, Sakai N. et al. Lack of myocardial perfusion immediately after successful thrombolysis: a predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation 1992; 85: 1699-1705.
4 Ito H, Maruyama A, Iwakura K. et al. Clinical implications of the ‘no reflow’ phenomenon: a predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 1996; 93: 223-228.
5 Patrono C, Baigent C, Hirsh J. et al. American College of Chest Physicians. Antiplatelet drugs: American College of Chest Phisicians Evidence-Based Clinical Practice Guidelines. Chest 2008; 33 (06) Suppl 1995-2335.
6 Michelson AD. Flow cytometry: a clinical test of platelet function. Blood 1996; 87: 4925-4936.
7 Furman MI, Barnard MR, Krueger LA. et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol 2001; 38: 1002-1006.
8 Lanza GA, Aurigemma C, Fattorossi A. et al. Changes in platelet receptor expression and leukocyte-platelet aggregate formation following exercise in cardiac Síndrome X. J Thromb Haemost 2006; 4: 1623-1625.
9 Aurigemma C, Fattorossi A, Sestito A. et al. Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise. Thromb Res 2007; 120: 901-909.
10 Aurigemma C, Scalone G, Fattorossi A. et al. Adenosine inhibition of adenosine diphosphate and thrombin-induced monocyte-platelet aggregates in cardiac syndrome X. Thromb Res 2009; 124: 116-120.
11 Scalone G, Coviello I, Barone L. et al. Brief low-workload myocardial ischaemia induces protection against exercise-related increase of platelet reactivity in patients with coronary artery disease. Heart 2010; 96: 263-268.
12 Van’t Hof AWJ, Liem A, Suryapranata H. et al. Angiographic Assessment of Myocardial Reperfusion in Patients Treated With Primary Angioplasty for Acute Myocardial Infarction: Myocardial Blush Grade. Circulation 1998; 97: 2302-2306.
13 Fitzgerald DJ, Roy L, Catella F. et al. Platelet activation in unstable coronary disease. N Engl J Med 1986; 315: 983-989.
14 Goto S, Saka H, Goto M. et al. Enhanced shear-induced platelet aggregation in acute coronary myocardial infarction. Circulation 1999; 99: 608-613.
15 Swahn E, Wallentin L. Platelet reactivity in unstable coronary disease. Thromb Haemost 1987; 57: 302-305.
16 Feng T, Yundai C, Lian C. et al. Assessment of coronary plaque characteristics by optical coherence tomography in patients with diabetes mellitus complicated with unstable angina pectoris. Atherosclerosis 2010; 213: 482-485.
17 Ott I, Neumann F-J, Gawaz M. et al. Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation 1996; 94: 1239-1246.
18 Geisler T, Kapp M, Gohring-Frischholz K. et al. Residual platelet activity is increased in clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary disease. Heart 2008; 94: 743-747.
19 Scalone G, Coviello I, Barone L. et al. Evidence of increased platelet reactivity in the first six months after acute ST segment elevation myocardial infarction. Thromb Res 2011; 128: 174-178.
20 Michelson AD, Barnard MR, Krueger LA. et al. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation 2001; 104: 1533-1537.
21 Danenberg HD, Kantak N, Grad E. et al. C-reactive protein promotes mono-cyte-platelet aggregation: an additional link to the inflammatory-thrombotic intricacy. Eur J Haematol 2007; 78: 246-252.
22 McGregor L, Martin J, McGregor JL. Platelet-leukocyte aggregates and derived microparticles in inflammation, vascular remodelling and thrombosis. Front Biosci 2006; 11: 830-837.
23 Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002; 105: 2130-2132.
24 Botto N, Sbrana S, Trianni G. et al. An increased platelet-leukocytes interaction at the culprit site of coronary artery occlusion in acute myocardial infarction: a pathogenic role for “no-reflow” phenomenon?. Int J Cardiol 2007; 12: 123-130.
25 Charron T, Jaffe R, Segev A. et al. Effects of distal embolisation on the timing of platelet and inflammatory cell activation in interventional coronary no-reflow. Thromb Res 2010; 126: 50-55.
26 Ramjane K, Han L, Jin C. The diagnosis and treatment of the no-reflow phenomenon in patients with myocardial infarction undergoing percutaneous coronary intervention. Exp Clin Cardiol 2008; 13: 121-128.
27 Michaels AD, Gibson CM, Barron HV. Microvascular dysfunction in acute myocardial infarction: focus on the role of platelet and inflammatory mediators in the no-reflow phenomenon. Am J Cardiol 2000; 85: 50-60.
28 Taniyama Y, Ito H, Iwakura K. et al. Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol 1997; 30: 1193-1199.
29 Wilson RF, Laxson DD, Lesser JR. et al. Intense microvascular constriction after angioplasty of acute thrombotic coronary arterial lesions. Lancet 1989; 1: 807-811.
30 Henriques JP, Haasdijk AP, Zijlstra F. Zwolle Myocardial Infarction Study Group. Outcome of primary angioplasty for acute myocardial infarction during routine duty hours versus during off-hours. J Am Coll Cardiol 2003; 41: 2138-2142.
31 Zijlstra F, Patel A, Jones M. et al. Clinical characteristics and outcome of patients with early (2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. Eur Heart J 2002; 23: 550-557.