Evaluation of the platelet count drop method for assessment of platelet function in comparison with "gold standard" light transmission aggregometry (original) (raw)

Abstract

Introduction: Hyporesponsiveness to antiplatelet agents has been linked to an increased risk of major adverse cardiovascular events. However, light transmission aggregometry (LTA), the gold standard methodology for assessing platelet function, requires expertise and is labour-intensive, which render its use in clinical settings impractical. We assessed whether platelet count drop (PCD), a technique widely available in any haematology laboratory, could replace LTA in testing for inhibition of platelet aggregation induced by antiplatelet agents. Materials and methods: One hundred and sixty-one coronary artery disease patients taking aspirin alone and 91 patients taking a combination of aspirin and clopidogrel were enrolled. Platelet aggregation was measured by LTA and PCD stimulated with 1.6 mM of arachidonic acid (AA) for aspirin and 5 and 20 μM of adenosine diphosphate (ADP) for clopidogrel. Results: Correlation between AA-induced LTA and PCD was inexistent (r = -0.043, p = 0.587), while correlation between ADP-induced LTA and PCD was low (r = 0.374, p b 0.0001 for ADP 5 μM and r = 0.402, p b 0001 for ADP 20 μM). PCD, whether stimulated with AA or ADP, overestimated platelet aggregation as assessed by LTA, by 13-18%. The wide 95% limits of agreement suggest that the assays can disagree significantly in individual patients. Conclusions: Although the PCD method is widely available in non-specialized laboratories, our results demonstrate that there is poor correlation with the current gold standard, i.e. LTA. Thus, PCD should not be used in replacement of LTA to assess antiplatelet responsiveness.

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  1. Platelet count drop (PCD) method poorly correlates with light transmission aggregometry (LTA), the gold standard.
  2. Inadequate platelet response was misclassified in 13-18% of cases when assessed by PCD compared to LTA.
  3. Study involved 252 coronary artery disease patients on aspirin or clopidogrel, with specific dosing regimens.
  4. PCD overestimated platelet aggregation by 13-18% and lacked agreement in identifying hyporesponsiveness to treatments.
  5. PCD should not replace LTA for assessing antiplatelet responsiveness due to significant discrepancies.

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References (32)

  1. Patrono C, Baigent C, Hirsh J, Roth G. Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:199S-233S.
  2. Fraker Jr TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J, et al. 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina. Circulation 2007;116:2762-72.
  3. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.
  4. Lordkipanidzé M, Pharand C, Palisaitis DA, Diodati JG. Aspirin resistance : Truth or dare. Pharmacol Ther 2006;112:733-43.
  5. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol 2005;45:1157-64.
  6. Wenaweser P, Dorffler-Melly J, Imboden K, Windecker S, Togni M, Meier B, et al. Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol 2005;45:1748-52.
  7. Cuisset T, Frere C, Quilici J, Barbou F, Morange PE, Hovasse T, 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;4:542-9.
  8. Gianetti J, Parri MS, Sbrana S, Paoli F, Maffei S, Paradossi U, et al. Platelet activation predicts recurrent ischemic events after percutaneous coronary angioplasty: a 6 months prospective study. Thromb Res 2006;118:487-93.
  9. Foussas SG, Zairis MN, Patsourakos NG, Makrygiannis SS, Adamopoulou EN, Handanis SM, et al. The impact of oral antiplatelet responsiveness on the long- term prognosis after coronary stenting. Am Heart J 2007;154:676-81.
  10. Cuisset T, Hamilos M, Sarma J, Sarno G, Wyffels E, Vanderheyden M, et al. Relation of low response to clopidogrel assessed with point-of-care assay to periprocedural myonecrosis in patients undergoing elective coronary stenting for stable angina pectoris. Am J Cardiol 2008;101:1700-3.
  11. Michelson AD. Platelet function testing in cardiovascular diseases. Circulation 2004;110:e489-93.
  12. Harrison P. Progress in the assessment of platelet function. Br J Haematol 2000;111: 733-44.
  13. Nicholson N, Panzer-Knodle S, Haas N, Taite B, Szalony J, Page J, et al. Assessment of platelet function assays. Am Heart J 1998;135:S170-8.
  14. Lordkipanidzé M, Pharand C, Nguyen TA, Schampaert E, Palisaitis DA, Diodati JG. Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients. Eur Heart J 2008;29:2877-85.
  15. Lordkipanidzé M, Pharand C, Schampaert E, Turgeon J, Palisaitis DA, Diodati JG. 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;28:1702-8.
  16. Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003;41:961-5.
  17. Frere C, Cuisset T, Quilici J, Camoin L, Carvajal J, Morange PE, 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;98:838-43.
  18. Buonamici P, Marcucci R, Migliorini A, Gensini GF, Santini A, Paniccia R, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007;49:2312-7.
  19. Geisler T, Grass D, Bigalke B, Stellos K, Drosch T, Dietz K, et al. The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score. J Thromb Haemost 2008;6:54-61.
  20. Rand ML, Leung R, Packham MA. Platelet function assays. Transfus Apher Sci 2003;28:307-17.
  21. Ryan WL, Hakenkamp K, Sullivan E. A new platelet function test. Thromb Res 1990;58:163-73.
  22. Lau WC, Walker CT, Obilby D, Wash MM, Carville DG, Guyer KE, et al. Evaluation of a BED-SIDE Platelet Function Assay: Performance and Clinical Utility. Ann Card Anaesth 2002;5:33-42.
  23. Campbell J, Ridgway H, Carville D. Plateletworks ® : a novel point of care platelet function screen. Mol Diagn Ther 2008;12:253-8.
  24. Lennon MJ, Gibbs NM, Weightman WM, McGuire D, Michalopoulos N. A comparison of Plateletworks and platelet aggregometry for the assessment of aspirin-related platelet dysfunction in cardiac surgical patients. J Cardiothorac Vasc Anesth 2004;18:136-40.
  25. Mobley JE, Bresee SJ, Wortham DC, Craft RM, Snider CC, Carroll RC. Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment for cardiac catheterization. Am J Cardiol 2004;93:456-8.
  26. Craft RM, Chavez JJ, Snider CC, Muenchen RA, Carroll RC. Comparison of modified Thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients. J Lab Clin Med 2005;145:309-15.
  27. Van Werkum JW, Kleibeuker M, Postma S, Bouman HJ, Elsenbert EHAM, Ten Berg JM, et al. A comparison between the Plateletworks-assay and light transmittance aggregometry for monitoring the inhibitory effects of clopidogrel. Int J Cardiol 2008, doi:10.1016/j.ijcard.2008.10.046.
  28. Santos MT, Valles J, Marcus AJ, Safier LB, Broekman MJ, Islam N, et al. Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment. J Clin Invest 1991;87:571-80.
  29. Valles J, Santos MT, Aznar J, Osa A, Lago A, Cosin J, et al. Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality : the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity. Circulation 1998;97:350-5.
  30. Patrignani P. Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease. Thromb Res 2003;110:281-6.
  31. Heptinstall S, Johnson A, Glenn JR, White AE. Adenine nucleotide metabolism in human blood-important roles for leukocytes and erythrocytes. J Thromb Haemost 2005;3:2331-9.
  32. Dyszkiewicz-Korpanty AM, Frenkel EP, Sarode R. Approach to the assessment of platelet function: comparison between optical-based platelet-rich plasma and impedance-based whole blood platelet aggregation methods. Clin Appl Thromb Hemost 2005;11:25-35.