Application of platelet function testing to the bedside

Summary

The ability to test platelet reactivity in clinical practice could help in making informed decisions on both initiation and titration of anti-platelet drug therapies. However, many barriers still remain to the effective implementation of such techniques. Many tests used in the research literature are not yet available for practical, clinical use. Platelet aggregometry, while informative and currently available for bedside use, needs additional research before routine clinical use can be recommended. This review will highlight and update contemporary issues of bedside platelet testing for the clinician and comment on future areas of clinical research.

Keywords

Clopidogrel - aspirin - platelet aggregation - platelet function tests - anti-platelet tests

• References

• 1 Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231: 232-235.
• 2 Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol 1971; 231: 235-237.
• 3 Quick AJ. Salicylates and bleeding: the aspirin tolerance test. Am J Med Sci 1966; 252: 265-269.
• 4 Michelson AD. Methods for the measurement of platelet function. Am J Cardiol 2009; 103 (Suppl. 03) 20A-26A.
• 5 Gremmel T, Steiner S, Seidinger D. et al. Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation. Thromb Haemost 2009; 101: 333-339.
• 6 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.
• 7 Penz SM, Reininger AJ, Toth O. et al. Glycoprotein Ibalpha inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques. Thromb Haemost 2007; 97: 435-443.
• 8 Alfonso F, Angiolillo DJ. Platelet function assessment to predict outcomes after coronary interventions: hype or hope?. J Am Coll Cardiol 2006; 48: 1751-1754.
• 9 Oestreich JH, Smyth SS, Campbell CL. Platelet function analysis: at the edge of meaning. Thromb Haemost 2009; 101: 217-219.
• 10 Lev EI. Aspirin resistance transient laboratory finding or important clinical entity?. J Am Coll Cardiol. 2009; 53: 678-680.
• 11 De Miguel A, Ibanez B, Badimon JJ. Clinical implications of clopidogrel resistance. Thromb Haemost 2008; 100: 196-203.
• 12 Zimmermann N, Hohlfeld T. Clinical implications of aspirin resistance. Thromb Haemost 2008; 100: 379-390.
• 13 Snoep JD, Hovens MM, Eikenboom JC. et al. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med 2007; 167: 1593-1599.
• 14 Eikelboom JW, Hirsh J, Weitz JI. et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650-1655.
• 15 Crescente M, Di Castelnuovo A, Iacoviello L. et al. PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a meta-analysis of 19 studies comprising 3,003 patients. Thromb Haemost 2008; 99: 1129-1131.
• 16 Sibbing D, Braun S, Morath T. et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009; 53: 849-856.
• 17 Smith Jr., SC, Allen J, Blair SN. et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006; 113: 2363-2372.
• 18 Patrono C. Aspirin as an antiplatelet drug. N Engl J Med 1994; 330: 1287-1294.
• 19 Santilli F, Rocca B, De Cristofaro R. et al. Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays: implications for aspirin “resistance“. J Am Coll Cardiol 2009; 53: 667-677.
• 20 Steinhubl SR, Talley JD, Braden GA. et al. Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation 2001; 103: 2572-2578.
• 21 Serebruany VL, Steinhubl SR, Berger PB. et al. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005; 45: 246-251.
• 22 Serebruany V, Pokov I, Kuliczkowski W. et al. Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease. Thromb Haemost. 2008; 100: 76-82.
• 23 Zhang JN, Bergeron AL, Yu Q. et al. Platelet aggregation and activation under complex patterns of shear stress. Thromb Haemost 2002; 88: 817-821.
• 24 Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-2494.
• 25 Ferreiro JL, Angiolillo DJ. Clopidogrel response variability: current status and future directions. Thromb Haemost 2009; 102: 7-14.
• 26 Hobson A, Curzen N. Improving outcomes with antiplatelet therapies in percutaneous coronary intervention and stenting. Thromb Haemost 2009; 101: 23-30.
• 27 Product labelling, VerifyNow IIb/IIIa [database on the Internet]. 2009 Available at: http://www.accumetrics.com/products/docs/IIb_IIIa/14320_IIBIIIA_Eng.pdf.
• 28 Product labelling, VerifyNow aspirin. 2009
• 29 Product labelling, VerifyNow P2Y₁₂ . 2009
• 30 Kleiman NS. Will measuring vasodilator-stimulated phosphoprotein phosphorylation help us optimize the loading dose of clopidogrel?. J Am Coll Cardiol 2008; 51: 1412-1414.
• 31 Geiger J, Teichmann L, Grossmann R. et al. Monitoring of clopidogrel action: comparison of methods. Clin Chem 2005; 51: 957-965.
• 32 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.
• 33 Plateletworks ADP and collagen [database on the Internet]. 2009 Available at: http://www.helena.com/Procedures/Pro190Rev6.pdf.
• 34 Lau WC, Waskell LA, Watkins PB. et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003; 107: 32-37.
• 35 Gasparyan AY, Watson T, Lip GY. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol 2008; 51: 1829-1843.
• 36 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961-965.
• 37 Marcucci R, Gori AM, Paniccia R. et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 2009; 119: 237-242.
• 38 Lasne D, Fiemeyer A, Chatellier G. et al. A study of platelet functions with a new analyzer using high shear stress (PFA 100) in patients undergoing coronary artery bypass graft. Thromb Haemost 2000; 84: 794-799.
• 39 Morgenstern E, Boeckel N, Luscher EF. Do ADP-activated platelets in vitro aggregate as discocytes?. Thromb Haemost 2007; 98: 73-76.
• 40 Harding SA, Din JN, Sarma J. et al. Flow cytometric analysis of circulating platelet-monocyte aggregates in whole blood: methodological considerations. Thromb Haemost 2007; 98: 451-456.
• 41 Simon T, Verstuyft C, Mary-Krause M. et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009; 360: 363-375.
• 42 Patti G, Nusca A, Mangiacapra F. et al. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol 2008; 52: 1128-1133.
• 43 Price MJ, Endemann S, Gollapudi RR. et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008; 29: 992-1000.
• 44 Mirkhel A, Peyster E, Sundeen J. et al. Frequency of aspirin resistance in a community hospital. Am J Cardiol 2006; 98: 577-579.
• 45 Angiolillo DJ, Shoemaker SB, Desai B. et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation 2007; 115: 708-716.
• 46 Neubauer H, Lask S, Engelhardt A, Mugge A. How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification. Thromb Haemost 2008; 99: 357-362.
• 47 Antiplatelet Trial Collaborators.. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
• 48 Lev EI, Patel RT, Maresh KJ. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol 2006; 47: 27-33.
• 49 Guthikonda S, Mangalpally K, Vaduganathan M. et al. Increased platelet sensitivity among individuals with aspirin resistance – platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy. Thromb Haemost 2008; 100: 83-89.
• 50 Gori AM, Marcucci R, Paniccia R. et al. Thrombotic events in high risk patients are predicted by evaluating different pathways of platelet function. Thromb Haemost 2008; 100: 1136-1145.
• 51 Shantsila E, Lip GY. Predicting thrombotic events: creating a complex approach for a complex condition. Thromb Haemost 2008; 100: 962-964.
• 52 Sugidachi A, Ogawa T, Kurihara A. et al. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel’s active meta-bolite. J Thromb Haemost 2007; 05: 1545-1551.
• 53 Jakubowski JA, Payne CD, Li YG. et al. A comparison of the antiplatelet effects of prasugrel and high-dose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry. Thromb Haemost 2008; 99: 215-222.
• 54 Wiviott SD, Braunwald E, McCabe CH. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
• 55 Calatzis A. Another view on prasugrel. Thromb Haemost 2009; 101: 12-13.
• 56 Serebruany V, Shalito I, Kopyleva O. Prasugrel development – claims and achievements. Thromb Haemost 2009; 101: 14-22.
• 57 Serebruany VL, Makarov LM. Future of oral antiplatelet therapy: four challenged hypotheses. Thromb Haemost 2009; 101: 1041-1043.