Cross validation of the Multiple Electrode Aggregometry

Jolanta M. Siller-Matula; Ghazaleh Gouya; Michael Wolzt; Bernd Jilma

doi:10.1160/TH08-10-0669

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(02): 397-403
DOI: 10.1160/TH08-10-0669

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Cross validation of the Multiple Electrode Aggregometry

A prospective trial in healthy volunteers

Authors

Jolanta M. Siller-Matula

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria
Ghazaleh Gouya

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria
Michael Wolzt

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria
Bernd Jilma

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria

Abstract

Summary

Several test systems exist for assessment of platelet function in patients under clopidogrel or aspirin therapy. The objective was to cross-validate the Multiple Electrode Aggregometry (MEA) with three other methods used for determining platelet reactivity under treatment with clopidogrel and aspirin. Platelet function was assessed by the MEA, Vasodilator Stimulated Phosphoprotein (VASP) phosphorylation assay, Platelet Function Analyzer-100 (PFA-100) and the Cone and Platelet Analyzer. Measurements were performed in blood from nine healthy volunteers at baseline, 2, 4, 6 and 72 hours after clopidogrel and aspirin loading. The apparent effect size for clopidogrel and aspirin was greatest for the MEA: treatment induced a 19-fold difference in the arachidonic acid-induced platelet aggregation and an 11-fold difference in the adenosine diphosphate-induced platelet aggregation before/after treatment. For comparison, aspirin and clopidogrel induced only 2.0– to 2.6 -fold changes in other tests (VASP assay, Cone and Platelet Analyzer and PFA-100). Maximal effects were seen 2 hours after aspirin loading and shorter than 72 hours after clopidogrel loading. In conclusion, aspirin and clopidogrel produce stronger signals in the MEA compared to several other methods.

Keywords

Antiplatelet - aspirin - clopidogrel - platelet function - Multiplate Analyzer

Full Text

References

References
1 Gurbel PA, O’Connor CM, Cummings CC. et al. Clopidogrel: the future choice for preventing platelet activation during coronary stenting?. Pharmacol Res 1999; 40: 107-111.
2 Siller-Matula J, Schror K, Wojta J. et al. Thienopyridines in cardiovascular disease: focus on clopidogrel resistance. Thromb Haemost 2007; 97: 385-393.
3 Sibbing D, von Beckerath O, Schomig A. et al. Impact of body mass index on platelet aggregation after administration of a high loading dose of 600 mg of clopidogrel before percutaneous coronary intervention. Am J Cardiol 2007; 100: 203-205.
4 Pamukcu B, Oflaz H, Oncul A. et al. The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events. J Thromb Thrombolysis 2006; 22: 103-110.
5 Cattaneo M. Resistance to antiplatelet drugs: molecular mechanisms and laboratory detection. J Thromb Haemost 2007; 05 (Suppl. 01) 230-237
6 Blindt R, Stellbrink K, de Taeye A. et al. The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis. Thromb Haemost 2007; 98: 1329-1334.
7 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.
8 Bonello L, Paganelli F, Arpin-Bornet M. et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 05: 1630-1636.
9 Matetzky S, Shenkman B, Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
10 Gurbel PA, Becker RC, Mann KG. et al. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007; 50: 1822-1834.
11 Varon D, Lider O, Dardik R. et al. Inhibition of integrin-mediated platelet aggregation, fibrinogen-binding, and interactions with extracellular matrix by nonpeptidic mimetics of Arg-Gly-Asp. Thromb Haemost 1993; 70: 1030-1036.
12 Savion N, Varon D. Impact--the cone and plate(let) analyzer: testing platelet function and anti-platelet drug response. Pathophysiol Haemost Thromb 2006; 35: 83-88.
13 Frossard M, Fuchs I, Leitner JM. et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation 2004; 110: 1392-1397.
14 Fuchs I, Frossard M, Spiel A. et al. Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS. J Thromb Haemost 2006; 04: 2547-2552.
15 Campo G, Valgimigli M, Gemmati D. et al. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY Study. J Am Coll Cardiol 2006; 48: 2178-2185.
16 Jilma B. Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired platelet dysfunction. J Lab Clin Med 2001; 138: 152-163.
17 Sibbing D, Braun S, Jawansky S. et al. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment. Thromb Haemost 2008; 99: 121-126.
18 Siller-Matula JM, Panzer S, Jilma B. Reproducibility and standardised reporting of the vasodilator-stimulated phosphoprotein phosphorylation assay. Platelets 2008; 19: 551-554.
19 Siller-Matula J, Lang I, Christ G. et al. Calcium channel blockers reduce the antiplatelet effect of clopidogrel. J Am Coll Cardiol 2008; 52: 1557-1563.
20 Aleil B, Ravanat C, Cazenave JP. et al. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost 2005; 03: 85-92.
21 Toth O, Calatzis A, Penz S. et al. Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood. Thromb Haemost 2006; 96: 781-788.
22 Mueller T, Dieplinger B, Poelz W. et al. Utility of whole blood impedance aggregometry for the assessment of clopidogrel action using the novel Multiplate(R) analyzer-comparison with two flow cytometric methods. Thromb Res 2007; 121: 249-258.
23 Jilma-Stohlawetz P, Hergovich N, Homoncik M. et al. Impaired platelet function among platelet donors. Thromb Haemost 2001; 86: 880-886.
24 Kotzailias N, Elwischger K, Sycha T. et al. Clopidogrel-induced platelet inhibition cannot be detected by the platelet function analyzer-100 system in stroke patients. J Stroke Cerebrovasc Dis 2007; 16: 199-202.
25 Panzer S, Eichelberger B, Koren D. et al. Monitoring survival and function of transfused platelets in Bernard-Soulier syndrome by flow cytometry and a cone and plate(let) analyzer (Impact-R). Transfusion 2007; 47: 103-106.
26 Morrison A, Hornsey VS, Prowse CV. et al. Use of the DiaMed Impact R to test platelet function in stored platelet concentrates. Vox Sang 2007; 93: 166-172.
27 Geiger J, Teichmann L, Grossmann R. et al. Monitoring of clopidogrel action: comparison of methods. Clin Chem 2005; 51: 957-965.
28 Jakubowski JA, Payne CD, Li YG. et al. A comparison of the antiplatelet effects of prasugrel and highdose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry. Thromb Haemost 2008; 99: 215-222.
29 Buerke M, Pittroff W, Meyer J. et al. Aspirin therapy: optimized platelet inhibition with different loading and maintenance doses. Am Heart J 1995; 130: 465-472.
30 Johnson A, Dovlatova N, Heptinstall S. Multiple electrode aggregometry and P2Y(12) antagonists. Thromb Haemost 2008; 99: 1127-1129.
31 Breugelmans J, Vertessen F, Mertens G. et al. Multiplate whole blood impedance aggregometry: A recent experience. Thromb Haemost 2008; 100: 725-726.
32 Shenkman B, Matetzky S, Fefer P. et al. Variable responsiveness to clopidogrel and aspirin among patients with acute coronary syndrome as assessed by platelet function tests. Thromb Res 2007; 122: 336-345.
33 Poulsen TS, Mickley H, Korsholm L. et al. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy. Thromb Res 2007; 120: 161-172.
34 Lordkipanidze M, Pharand C, Schampaert E. et al. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 2007; 28: 1702-1708.
35 Gurbel PA, Bliden KP, Samara W. et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J Am Coll Cardiol 2005; 46: 1827-1832.
36 Karon BS, Wockenfus A, Scott R. et al. Aspirin responsiveness in healthy volunteers measured with multiple assay platforms. Clin Chem 2008; 54: 1060-1065.