Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction

Marie-Geneviève Huisse; Emilie Lanoy; Didier Tcheche; Laurent J. Feldman; Annie Bezeaud; Eduardo Anglès-Cano; Murielle Mary-Krause; Dominique de Prost; Marie-Claude Guillin; Gabriel P. Steg

doi:10.1160/TH06-11-0621

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(02): 420-426
DOI: 10.1160/TH06-11-0621

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction

Authors

Marie-Geneviève Huisse

¹AP-HP, Hôpital Bichat, Departments of Haematology and

⁴CIB PhenoGen; University Paris7-Denis Diderot

⁵INSERM U698; University Paris7-Denis Diderot
Emilie Lanoy

³U720 ; University Paris7-Denis Diderot

⁶University Pierre et Marie Curie-Paris 6, Paris, France
Didier Tcheche

²Departments of Cardiology
Laurent J. Feldman

²Departments of Cardiology

⁵INSERM U698; University Paris7-Denis Diderot
Annie Bezeaud

⁴CIB PhenoGen; University Paris7-Denis Diderot

⁵INSERM U698; University Paris7-Denis Diderot
Eduardo Anglès-Cano

⁵INSERM U698; University Paris7-Denis Diderot
Murielle Mary-Krause

³U720 ; University Paris7-Denis Diderot

⁶University Pierre et Marie Curie-Paris 6, Paris, France
Dominique de Prost

⁴CIB PhenoGen; University Paris7-Denis Diderot

⁵INSERM U698; University Paris7-Denis Diderot
Marie-Claude Guillin

¹AP-HP, Hôpital Bichat, Departments of Haematology and

⁴CIB PhenoGen; University Paris7-Denis Diderot

⁵INSERM U698; University Paris7-Denis Diderot
Gabriel P. Steg

²Departments of Cardiology

⁵INSERM U698; University Paris7-Denis Diderot

Abstract

Summary

We tested the hypothesis that selected prothrombotic biomarkers might be associated with early spontaneous coronary recanalization in patients with ST-segment elevation acute myocardial infarction (STEMI). We prospectively enrolled 123 patients with STEMI including 53 patients with spontaneous coronary recanalization (cases) and 70 patients with persistent occlusion (controls) at the time of emergent coronary angiography and before angioplasty. All had received aspirin and heparin. Blood samples were collected immediately before angioplasty to measure soluble P-selectin, circulating microparticles originating from platelets (PMPs), granulocytes (GMPs), endothelial cells (EMPs); tissue factor-associated MP (TF-MP); soluble platelet glycoprotein V (sGPV) and prothrombin F1+2; tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin (PAP). A sub-group of 70 patients (35 cases, 35 controls) was available for flow cytometry analysis of platelet P-selectin and activated GPIIb-IIIa. Baseline clinical characteristics did not differ between groups except for more frequent hypertension and dyslipidemia in controls. Platelet activation markers and PMP did not differ between the two groups. Controls had higher numbers of EMPs and GMPs compared to cases, but the difference was no longer significant when corrected for risk factors. Controls differed from cases by higher plasma levels of sGPV [64 (47–84) ng/ml vs. 53 (44–63) ng/ml] and PAP [114(65–225) ng/ml vs. 88 (51–147) ng/ml].The difference persisted after adjustment for risks factors (p=0.031 and 0.037, respectively). Persistent occlusion of the infarct related artery is associated with some markers related to higher thrombin (sGPV) and plasmin (PAP) production but is not associated with markers of platelet activation.

Keywords

Myocardial infarction - thrombin - soluble glycoproteinV - endothelial injury - plasmin-antiplasmin

Full Text

References

References
1 Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005; 111: 3481-3488.
2 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 29: 101 841-843.
3 Morel O, Toti F, Hugel B. et al. Procoagulant Micro-particles. Disrupting the Vascular Homeostasis Equation? Arterioscler Thromb Vasc Biol 2006; 26: 2594-2604.
4 Juhan-Vague I, Alessi MC. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 1997; 78: 656-660.
5 Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13-20.
6 Steg PG, Himbert D, Benamer H. et al. Conservative management of patients with acute myocardial infarction and spontaneous acute patency of the infarctrelated artery. Am Heart J 1997; 134: 248-252.
7 Brodie BR, Stuckey TD, Hansen C. et al. Benefit of coronary reperfusion before intervention on outcomes after primary angioplasty for acute myocardial infarction. Am J Cardiol 2000; 85: 13-18.
8 The Thrombolysis in Myocardial Infarction(TIMI) trial.. Phase I findings. TIMI Study Group. N Engl J Med 1985; 312: 932-936.
9 Nieuwland R, Berckmans RJ, McGregor S. et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95: 930-935.
10 Key NS, Slungaard A, Dandelet L. et al. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood 1998; 91: 4216-4223.
11 Aleil B, Meyer N, Wolff V. et al. Plasma glycoprotein V levels in the general population: Normal distribution, associated parameters and implications for clinical studies. Thromb Haemost 2006; 96: 505-511.
12 Montes R, Paramo JA, Angles-Cano E. et al. Development and clinical application of a new ELISA as say to determine plasmin-alpha2-antiplasmin complexes in plasma. Br J Haematol 1996; 92: 979-985.
13 Yip HK, Chang LT, Sun CK. et al. Platelet activity is a biomarker of cardiac necrosis and predictive of untoward clinical outcomes in patients with acute myocardial infarction undergoing primary coronary stenting. Circ J 2006; 70: 31-36.
14 Aleil B, Mossard JM, Wiesel ML. et al. Increased plasma levels of soluble platelet glycoprotein V in patients with acute myocardial infarction. J Thromb Haemost 2003; 1: 1846-1847.
15 Morel O, Hugel B, Jesel L. et al. Circulating procoagulant microparticles and soluble GPV in myocardial infarctiontreated by primary percutaneous transluminal coronary angioplasty. A possible role for GPIIb-IIIa antagonists. J Thromb Haemost 2004; 2: 1118-1126.
16 Pernerstorfer T, Eichler HG, Stohlawetz P. et al. Effects of heparin and aspirin on circulatingP-selectin, E-selectin and von Willebrand Factor levels in healthy men. Atherosclerosis 2001; 155: 389-393.
17 McKenzie ME, Malinin AI, Bell CR. et al. Aspirin inhibits surface glycoprotein IIb/IIIa, P-selectin, CD63, and CD107 a receptor expression on human platelets. Blood Coagul Fibrinolysis 2003; 14: 249-253.
18 Serebruany VL, Gurbel PA, Murugesan SR. et al. Depressed plasma platelet-activating factor acetylhydrolase in patients presenting with acute myocardial infarction. Cardiology 1998; 90: 127-130.
19 Bernal-Mizrachi L, Jy W, Jimenez JJ. et al. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J 2003; 145: 962-970.
20 Lip GY, Blann AD, Beevers DG. Prothrombotic factors, endothelial function and left ventricular hypertrophy in isolated systolic hypertension compared with systolic-diastolic hypertension. J Hypertens 1999; 17: 1203-1207.
21 Preston RA, Jy W, Jimenez JJ. et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension 2003; 41: 211-217.
22 Falati S, Liu Q, Gross P. et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197: 1585-1598.
23 Chironi G, Simon A, Hugel B. et al. Circulating leukocyte-derived microparticle spredict subclinical atherosclerosis burden in a symptomatic subjects. Arterioscler Thromb Vasc Biol 2006; 26: 2775-2780.
24 Koga H, Sugiyama S, Kugiyama K. et al. Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2005; 45: 1622-1630.
25 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-2652.
26 Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999; 274: 23111-23118.
27 Suefuji H, Ogawa H, Yasue H. et al. Increased plasma tissue factor levels in acute myocardial infarction. Am Heart J 1997; 134: 253-259.
28 Bonderman D, Teml A, Jakowitsch J. et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood 2002; 99: 2794-2800.
29 Rauch U, Bonderman D, Bohrmann B. et al. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: 170-175.
30 Schwertz H, Tolley ND, Foulks JM. et al. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J Exp Med 2006; 203: 2433-2440.
31 Steppich B, Mattisek C, Sobczyk D. et al. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction. Thromb Haemost 2005; 93: 35-39.
32 Ott I, Malcouvier V, Schomig A. et al. Proteolysis of tissue factor pathway inhibitor-1 by thrombolysis in acute myocardial infarction. Circulation 2002; 105: 279-281.
33 Belaaouaj AA, Li A, Wun TC. Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation. J Biol Chem 2000; 275: 27123-27128.
34 Ravanat C, Freund M, Mangin P. et al. GPV is a marker of in vivo platelet activation--study in arat thrombosismodel. Thromb Haemost 2000; 83: 327-333.
35 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; 15: 1202-1212.
36 Tschöpl M, Tsakiris DA, Marbet GA. et al. Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty. Arterioscler Thromb Vasc Biol 1997; 17: 3208-3214.
37 Rabie T, Strehl A, Ludwig A. et al. Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V. J Biol Chem 2005; 15: 14462-14468.
38 Thogersen AM, Jansson JH, Boman K. et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 1998; 98: 2241-2247.
39 Ridker PM, Brown NJ, Vaughan DE. et al. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. Circulation 2004; 109 (Suppl. 01) IV6-19.
40 Barron HV, Cannon CP, Murphy SA. et al. Association between white blood cell count, epicardial blood flow, myocardial perfusion, and clinical outcomes in the setting of acute myocardial infarction: a thrombolysis in myocardial infarction 10 substudy. Circulation 2000; 102: 2329-2334.
41 Kirtane AJ, Bui A, Murphy SA. et al. Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction. Am J Cardiol 2004; 93: 532-536.
42 Sambola A, Osende J, Hathcock J. et al. Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity. Circulation 2003; 107: 973-977.
43 Yusuf S, Mehta SR, Chrolavicius S. et al. OASIS-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. J Am Med Assoc 2006; 295: 1519-1530.
44 Lincoff AM, Bittl JA, Kleiman NS. et al. REPLACE-1 Investigators. Comparison of bivalirudin versus heparin during percutaneous coronary intervention(the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events[REPLACE]-1 trial). Am J Cardiol 2004; 93: 1092-1096.
45 Stone GW, Bertrand M, Colombo A. et al. Acute Catheterization and Urgent Intervention Triage strategY(ACUITY) trial: study design and rationale. Am Heart J 2004; 148: 764-775.
46 De Luca G, Suryapranata H, Ottervanger JP. et al. Circadian variation in myocardial perfusion and mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty. Am Heart J 2005; 150: 1185-1189.