Relationship between high platelet turnover and platelet function in high-risk patients with coronary artery disease on dual antiplatelet therapy

Francesca Cesari; Rossella Marcucci; Roberto Caporale; Rita Paniccia; Eloisa Romano; Gian Franco Gensini; Rosanna Abbate; Anna Maria Gori

doi:10.1160/TH08-01-0002

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(05): 930-935
DOI: 10.1160/TH08-01-0002

Platelets and Blood Cells

Schattauer GmbH

Relationship between high platelet turnover and platelet function in high-risk patients with coronary artery disease on dual antiplatelet therapy

Francesca Cesari

¹Department of Medical and Surgical Critical Care, Thrombosis Centre; Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Rossella Marcucci

¹Department of Medical and Surgical Critical Care, Thrombosis Centre; Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Roberto Caporale

²Central Laboratory, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Rita Paniccia

¹Department of Medical and Surgical Critical Care, Thrombosis Centre; Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Eloisa Romano

¹Department of Medical and Surgical Critical Care, Thrombosis Centre; Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Gian Franco Gensini

³Centro S. Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy

,

Rosanna Abbate

¹Department of Medical and Surgical Critical Care, Thrombosis Centre; Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Anna Maria Gori

¹Department of Medical and Surgical Critical Care, Thrombosis Centre; Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

› Author Affiliations

Abstract

Summary

A high platelet turnover rate produce a population of immature reticulated platelets (RP) that could confer, despite of antiplatelet drugs, a residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. To assess the influence of RP on platelet reactivity in CAD patients on dual antiplatelet therapy we measured RP in 372 patients by using the Sysmex XE-2100 haematology analyzer and platelet function by optical platelet aggregometry (PA) on platelet-rich-plasma induced by 1 mmol arachidonic acid (AA-PA) and 10 μM ADP (ADP-PA). RPR was defined as either AA-PA >20% or ADP-PA >70%. RP were expressed as a percentage of RP of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (higly fluorescent immature platelet fraction; H-IPF). Moderate but significant positive correlations between PA, IPF, H-IPF, and mean platelet volume (MPV) were found. According to tertiles of IPF, H-IPF and MPV, a significant trend for an increase of platelet aggregation by AA and ADP was evidenced. Furthermore, a significant difference for IPF, H-IPF and MPV between patients with and without RPR was observed. A linear regression analysis showed that IPF, H-IPF and MPV significantly affected PA measured by AA and ADP. At multivariate linear regression analysis these associations were confirmed. Moreover, a logistic regression analysis demonstrated that IPF, H-IPF and MPV significantly influenced the risk of RPR, and in the multivariate model these results remained significant. This study indicates that a high rate of platelet turnover is a new mechanism associated with platelet reactivity in high risk CAD patients on dual antiplatelet therapy.

Keywords

Antiplatelet therapy - CAD patients - platelet turnover - platelet reactivity - reticulated platelets

Full Text

References

References
1 Ault KA, Rinder HM, Mitchell J. et al. The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. Am J Clin Pathol 1992; 98: 637-646.
2 Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991; 338: 1409-1411.
3 Nakamura T, Uchiyama S, Yamazaki M. et al. Flow cytometric analysis of reticulated platelets in patients with ischemic stroke. Thromb Res 2002; 106: 171-177.
4 Lakkis N, Dokainish H, Abuzahara M. et al. Reticulated platelets in acute coronary syndrome: a marker of platelet activity. J Am Coll Cardiol 2004; 10: 2087-2098.
5 Gurbel PA, Bliden KP, Guyer K. et al. Platelet reactivity in patients and recurrent events post-stenting. Results of the PREPARE POST-STENTING study. J Am Coll Cardiol 2005; 46: 1820-1826.
6 Marcucci R, Paniccia R, Antonucci E. et al. Usefulness of aspirin resistance after percutaneous coronary intervention for acute myocardial infarction in predicting one-year major adverse coronary events. Am J Cardiol 2006; 98: 1156-1159.
7 Buonamici P, Marcucci R, Migliorini A. et al. Impact of platelet reactivity following clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007; 49: 2312-2317.
8 Bliden KP, Di Chiara J, Tantry US. et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate?. J Am Coll Cardiol 2007; 49: 657-666.
9 Chen WH, Lee PY, Ng W. et al. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary interventions despite clopidogrel pre-treatment. J Am Coll Cardiol 2004; 43: 1122-1126.
10 Cuisset T, Frere C, Quilici J. et al. High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome. J Thromb Haemost 2006; 4: 542-549.
11 Frere C, Cuisset T, Quilici J. et al. ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome. Thromb Haemost 2007; 98: 838-843.
12 Guthikonda S, Lev EI, Patel R. et al. Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin. J Thromb Haemost 2007; 5: 490-496.
13 Braunwald E, Antman EM, Beasley JW. et al. ACC/ AHA Guideline Update for the Management of Patients with Unstable Angina and Non-ST-segment Elevation of Myocardial Infarction-summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol 2002; 40: 1366-1374.
14 Cifkova R, Erdine S, Fagard R. et al. ESH/ESC Hypertension Guidelines Committee Practice guidelines for primary care physicians: 2003 ESH/ESC Hypertension guidelines. J Hypertens 2003; 21: 1779-1786.
15 Report of the expert committee on the diagnosis and classification of diabetes mellitus Diabetes Care 2003; 26: 5-20.
16 Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adult (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421.
17 Perneby C, Wallén NH, Rooney C. et al. Dose- and time-dependent antiplatelet effects of aspirin. Thromb Haemost 2006; 95: 652-658.
18 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961-965.
19 Geisler T, Langer H, Wydymus M. et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 2006; 27: 2420-2425.
20 Marcucci R, Gori AM, Paniccia R. et al. Residual platelet reactivity is associated with clinical and laboratory characteristics in patients with ischemic heart disease undergoing PCI on dual antiplatelet therapy. Atherosclerosis 2007; 195: 217-223.
21 Briggs C, Kunka S, Hart D. et al. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004; 126: 93-99.
22 Kario K, Matsuo T, Nakao K. Cigarette smoking increases the mean platelet volume in the elderly patients with risk factors for atherosclerosis. Clin Lab Haematol 1992; 14: 281-287.
23 Papanas N, Symeonidis G, Maltezos E. et al. Mean platelet volume in patients with type 2 diabetes mellitus. Platelets 2004; 15: 475-478.
24 Abbate R, Boddi M, Prisco D. et al. Ability of whole blood aggregometer to detect platelet hyperaggregability. Am J Clin Pathol 1989; 91: 159-164.
25 Coban E, Ozdogan M, Yazicioglu G. et al. The mean platelet volume in patients with obesity. Int J Clin Pract 2005; 59: 981-982.
26 Nadar S, Blann AD, Lip GY. Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. Ann Med 2004; 36: 552-557.
27 Pathansali R, Smith N, Bath P. Altered megakaryocyte- platelet haemostatic axis in hypercholesterolaemia. Platelets 2001; 12: 292-297.
28 Pizzulli L, Yang A, Martin JF. et al. Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain. Eur Heart J 1998; 19: 80-84.
29 Huczek Z, Kochman J, Filipiak KJ. et al. Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. J Am Coll Cardiol 2005; 46: 284-290.
30 Yang A, Pizzulli L, Luderitz B. Mean platelet volume as a marker of restenosis after percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris. Thromb Res 2006; 117: 371-377.
31 Glud T, Schnidt EB, Kristensen SD. et al. Platelet number and volume during myocardial infarction in relation to infarct size. Acta Med Scand 1986; 220: 401-405.
32 Ylmanaz MB, Akin Y, Biyikoglu SF. et al. Left ventricular thrombosis is associated with increased mean platelet volume in patients with dilated cardiomyopathy and sinus rhytm. Acta Cardiol 2004; 59: 41-45.
33 Sewell R, Ibbotson RM, Phillips R. et al. High mean platelet volume after myocardial infarction: is due to consumption of small platelets?. Br Med J 1984; 289: 1576-1578.
34 Jakubowski JA, Thompson CB, Vaillancourt R. et al. Arachidonic acid metabolism by platelets of differing size. Br J Haematol 1983; 53: 503-511.
35 Martin JF, Trowbridge EA, Salmon GL. et al. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nucler DNA concentration. Thromb Res 1983; 32: 443-460.
36 Tschoepe D, Roesen P, Kauffmann L. et al. Evidence for abnormal platelet glycoprotein expression in diabetes mellitus. Eur J Clin Invest 1990; 20: 166-170.
37 Peng J, Friese P, Wolf RF. et al. Relative reactivity of platelets from thrombopoietin and intereleukin-6 treated dogs. Blood 1996; 87: 4158-4163.
38 Stohlawetz P, Folman CC, von dem Borne AE. et al. Effects of endotoxemia on thrombopoiesis in men. Thromb Haemost 1999; 81: 613-617.