Platelet Reactivity in Acute Coronary Syndromes: Evidence for Differences in Platelet Behaviour between Unstable Angina and Myocardial Infarction

Anthony Mathur; Monique S. C. Robinson; James Cotton; John F. Martin; Jorge D. Erusalimsky

doi:10.1055/s-0037-1615952

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(06): 989-994
DOI: 10.1055/s-0037-1615952

Review Article

Schattauer GmbH

Platelet Reactivity in Acute Coronary Syndromes: Evidence for Differences in Platelet Behaviour between Unstable Angina and Myocardial Infarction

Authors

Anthony Mathur
Monique S. C. Robinson

¹Haemostasis Research Unit, Department of Haematology, University College London, London, UK
James Cotton
John F. Martin
Jorge D. Erusalimsky

Abstract

Summary

Previous work has shown that P-selectin and mean platelet volume, two markers associated with platelet reactivity, are elevated in acute coronary syndromes. This study investigated the possibility that these markers may define unstable angina (UA) and acute myocardial infarction (MI) as two separate conditions based on platelet behaviour. Mean platelet volume (MPV) was higher in UA patients (n = 15) than in those diagnosed with MI (n = 15) (10.7 ± 0.25 fL, vs. 9.8 ± 0.27 fL, P = 0.005). Platelet count was lower in UA than in MI (215 ± 13 × 10⁹/L vs. 271 ± 20 × 10⁹/L, P = 0.03). The percentage of platelets expressing P-selectin was higher in MI than in UA (9.1 ± 1.9% vs. 4.2 ± 0.85%, P = 0.03). This parameter was positively correlated with MPV in UA (r = 0.5, P = 0.04) but negatively correlated in MI (r = -0.6, P = 0.01), with no correlation for ACS as a whole (r = –0.32, P = 0.1). Our results suggest that in MI there is an acute process of generalised platelet activation that is unrelated to changes in MPV, whereas in UA there is an ongoing process of platelet consumption that leads to an increase in platelet size to compensate for a persistent decrease in platelet count. This study suggests that there is a fundamental difference in platelet biology between these two diseases.

Key words

Platelets - P-selectin - mean platelet volume - unstable angina - myocardial infarction

Full Text

References

References
1 Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM. Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications. Circulation 1989; 80: 198-205.
2 Gurbel PA, Kereiakes DJ, Dalesandro MR, Bahr RD, O’Connor CM, Serebruany VL. Role of soluble and platelet-bound P-selectin in discriminating cardiac from noncardiac chest pain at presentation in the emergency department. Am Heart J 2000; 139: 320-8.
3 Ault KA, Cannon CP, Mitchell J, McCahan J, Tracy RP, Novotny WF, Reimann JD, Braunwald E. Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol 1999; 33: 634-9.
4 Becker RC, Tracy RP, Bovill EG, Mann KG, Ault K. The clinical use of flow cytometry for assessing platelet activation in acute coronary syndromes. TIMI-III Thrombosis and Anticoagulation Group. Coron Artery Dis 1994; 5: 339-45.
5 Itoh T, Nakai K, Ono M, Hiramori K. Can the risk for acute cardiac events in acute coronary syndrome be indicated by platelet membrane activation marker P-selectin?. Coron Artery Dis 1995; 6: 645-50.
6 Martin JF, Plumb J, Kilbey RS, Kishk YT. Changes in volume and density of platelets in myocardial infarction. Br Med J (Clin Res Ed) 1983; 287: 456-9.
7 Pizzulli L, Yang A, Martin JF, Luderitz B. Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain. Eur Heart J 1998; 19: 80-4.
8 Hsu-Lin S, Berman CL, Furie BC, August D, Furie B. A platelet membrane protein expressed during platelet activation and secretion. Studies using a monoclonal antibody specific for thrombin-activated platelets. J Biol Chem 1984; 259: 9121-6.
9 Ushiyama S, Laue TM, Moore KL, Erickson HP, McEver RP. Structural and functional characterization of monomeric soluble P-selectin and comparison with membrane P-selectin. J Biol Chem 1993; 268: 15229-37.
10 Ikeda H, Nakayama H, Oda T, Kuwano K, Muraishi A, Sugi K, Koga Y, Toshima H. Soluble form of P-selectin in patients with acute myocardial infarction. Coron Artery Dis 1994; 5: 515-8.
11 Ikeda H, Takajo Y, Ichiki K, Ueno T, Maki S, Noda T, Sugi K, Imaizumi T. Increased soluble form of P-selectin in patients with unstable angina. Circulation 1995; 92: 1693-6.
12 Shimomura H, Ogawa H, Arai H, Moriyama Y, Takazoe K, Hirai N, Kaikita K, Hirashima O, Misumi K, Soejima H, Nishiyama K, Yasue H. Serial changes in plasma levels of soluble P-selectin in patients with acute myocardial infarction. Am J Cardiol 1998; 81: 397-400.
13 Martin J. The relationship between megakaryocyte ploidy and platelet volume. Blood Cells 1989; 15: 108-21.
14 Erusalimsky JD, Martin JF. The regulation of megakaryocyte polyploidization and its implications for coronary artery occlusion. Eur J. Clin Invest 1993; 23: 1-9.
15 Cameron HA, Phillips R, Ibbotson RM, Carson PH. Platelet size in myocardial infarction. Br Med J (Clin Res Ed) 1983; 287: 449-51.
16 Hendra TJ, Oswald GA, Yudkin JS. Increased mean platelet volume after acute myocardial infarction relates to diabetes and to cardiac failure. Diabetes Res Clin Pract 1988; 5: 63-9.
17 Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991; 338: 1409-1411.
18 Brown AS, Hong Y, de Belder A, Beacon H, Beeso J, Sherwood R, Edmonds M, Martin JF, Erusalimsky JD. Megakaryocyte ploidy and platelet changes in human diabetes and atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17: 802-7.
19 Braunwald E. Unstable angina. A classification. Circulation 1989; 80: 410-4.
20 Antman EM, and Braunwald E. Acute myocardial infarction. In: Braunwald E.. ed Heart Disease: a textbook of cardiovascular medicine. Philadelphia: W B Saunders; 1997: 1210.
21 Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998; 279: 1643-50.
22 Kishk YT, Trowbridge EA, Martin JF. Platelet volume subpopulations in acute myocardial infarction: an investigation of their homogeneity for smoking, infarct size and site. Clin Sci 1985; 68: 419-25.
23 Trowbridge EA, Martin JF. The platelet volume distribution: a signature of the prethrombotic state in coronary heart disease?. Thromb Haemost 1987; 58: 714-7.
24 Behrens WE. Mediterranean macrothrombocytopenia. Blood 1975; 46: 199-208.
25 Martin JF, Trowbridge EA, Salmon G, Plumb J. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res 1983; 32: 443-60.
26 Corash L, Chen HY, Levin J, Baker G, Lu H, Mok Y. Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume. Blood 1987; 70: 177-85.
27 Levin J, Bessman JD. The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age. J Lab Clin Med 1983; 101: 295-307.
28 Martin JF, Daniel TD, Trowbridge EA. Acute and chronic changes in platelet volume and count after cardiopulmonary bypass induced thrombocytopenia in man. Thromb Haemost 1987; 57: 55-8.
29 Kaushansky K. Thrombopoietin: the primary regulator of platelet production. Blood 1995; 86: 419-31.
30 Rentrop KP. Thrombi in acute coronary syndromes: revisited and revised. Circulation 2000; 101: 1619-26.
31 Kjeldsen SE, Weder AB, Egan B, Neubig R, Zweifler AJ, Julius S. Effect of circulating epinephrine on platelet function and hematocrit. Hypertension 1995; 25: 1096-105.
32 Kristensen SD, Bath PM, Martin JF. Differences in bleeding time, aspirin sensitivity and adrenaline between acute myocardial infarction and unstable angina. Cardiovasc Res 1990; 24: 19-23.
33 Stubbs PJ, Laycock J, Alaghband-Zadeh J, Carter G, Noble MIM. Circulating stress hormone and insulin concentrations in acute coronary syndromes: Identification of insulin resistance on admission. Clin Sci 1999; 96: 589-95.
34 Lefer AM, Weyrich AS, Buerke M. Role of selectins, a new family of adhesion molecules, in ischaemia-reperfusion injury. Cardiovasc Res 1994; 28: 289-94.
35 Fitzgerald DJ, Catella F, Roy L, FitzGerald GA. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988; 77: 142-50.
36 Gurbel PA, Serebruany VL, Shustov AR, Bahr RD, Carpo C, Ohman EM, Topol EJ. Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary Arteries. J Am Coll Cardiol 1998; 31: 1466-73.
37 Moser M, Nordt MD, Peter K, Ruef J, Kohler B, Schmittner M, Smalling R, Kubler W, Bode C. Platelet function during and after thrombolytic therapy for acute myocardial infarction with reteplase, alteplase, or streptokinase. Circulation 1999; 100: 1858-64.
38 Nidorf SM, Sturm M, Strophair J, Kendrew PJ, Taylor RR. Whole blood aggregation, thromboxane release and the lyso derivative of platelet activating factor in myocardial infarction and unstable angina. Cardiovasc Res 1989; 23: 273-8.
39 Nomura S, Kagawa H, Ozaki Y, Nagahama M, Yoshimura C, Fukuhara S. Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies. Thromb Res 1999; 95: 205-13.
40 Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99: 2192-217.
41 Giles H, Smith RE, Martin JF. Platelet glycoprotein IIb-IIIa and size are increased in acute myocardial infarction. Eur J. Clin Invest 1994; 24: 69-72.