Hirudin anticoagulation allows more rapid determination of P2Y12 inhibition by the VerifyNow P2Y12 assay

Wael Sumaya; Rebecca L. Daly; Sonal Mehra; Amrita J. Dhutia; Kate E. Howgego; Rosemary Ecob; Heather M. Judge; Allison C. Morton; Robert F. Storey

doi:10.1160/TH12-10-0718

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 109(03): 550-555
DOI: 10.1160/TH12-10-0718

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Hirudin anticoagulation allows more rapid determination of P2Y₁₂ inhibition by the VerifyNow P2Y12 assay

Wael Sumaya

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Rebecca L. Daly

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Sonal Mehra

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Amrita J. Dhutia

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Kate E. Howgego

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Rosemary Ecob

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Heather M. Judge

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Allison C. Morton

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

,

Robert F. Storey

¹Department of Cardiovascular Science, University of Sheffield, Northern General Hospital, Sheffield, UK

› Author Affiliations

Abstract

Summary

VerifyNow (VN) P2Y12 is a point-of-care assay used to assess response to P2Y12 inhibitors. Sodium citrate (citrate) is the standard anticoagulant used for this assay but requires a pre-incubation period. Hirudin is an alternative anticoagulant for platelet function studies that maintains physiological divalent cation levels. We investigated whether hirudin anticoagulation might allow more rapid testing of P2Y₁₂ inhibition at the time of percutaneous coronary intervention (PCI). Blood was collected from the arterial sheath of aspirin-treated patients undergoing elective, urgent or emergency coronary angiography ± PCI and aliquots were anticoagulated with either citrate or hirudin. For each anticoagulant, VN P2Y12 was performed both immediately and after 20 minutes. A total of 98 patients were included in this study following pre-treatment with clopidogrel (n = 88), prasugrel (n = 6) or no P2Y₁₂ inhibitor (n = 4). PRU with hirudin immediately (PRU_H_Imm) and PRU with citrate 20 minutes post sampling (PRU_C_20) were very strongly correlated (R = 0.95) though PRU_H_Imm tended to be lower than PRU_C_20 so that optimal correlation was estimated by the equation PRU_H_Imm = 0.95 x PRU_C_20 (p < 0.001). Bland-Altman plots showed good agreement between PRU_H_Imm and (0.95 x PRU_C_20). Platelet reactivity was more stable over the studied time course with hirudin as compared to citrate. We therefore conclude that VN P2Y12 with hirudin anticoagulation can be performed more rapidly and results are strongly correlated with delayed citrate measurements. Further studies are warranted to assess the utility of this method for improving clinical outcomes in patients undergoing PCI.

Keywords

P2Y₁₂ - VerifyNow - citrate - hirudin - PCI - myocardial infarction

Full Text

References

References
1 Levine GN, Bates ER, Blankenship JC. et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011; 124: 2574-2609.
2 Cattaneo M, Podda GM. State of the art of new P2Y12 antagonists. Int Emerg Med 2010; 5: 385-391.
3 Gurbel PA, Tantry US. Clopidogrel resistance?. Thromb Res 2007; 120: 311-321.
4 Barragan P, Bouvier JL, Roquebert PO. et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003; 59: 295-302.
5 Grove EL, Storey RF, Wurtz M. Platelet function testing in atherothrombotic disease. Curr Pharm Des. 2012; Epub ahead of print.
6 Malinin A, Pokov A, Swaim L. et al. Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel. Meth Find Exp Clin Pharmacol 2006; 28: 315-322.
7 Pittens CA, Bouman HJ, van Werkum JW. et al. Comparison between hirudin and citrate in monitoring the inhibitory effects of P2Y12 receptor antagonists with different platelet function tests. Journal of thrombosis and haemostasis : J Thromb Haemost 2009; 7: 1929-1932.
8 Judge HM, Buckland RJ, Sugidachi A. et al. Relationship between degree of P2Y12 receptor blockade and inhibition of P2Y12-mediated platelet function. Thromb Haemost 2010; 103: 1210-1217.
9 Brar SS, ten Berg J, Marcucci R. et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol 2011; 58: 1945-1954.
10 Kaiser AF, Neubauer H, Franken CC. et al. Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions. Platelets 2012; 23: 359-367.
11 Zhang HZ, Yu LH, Kim MH. Effect of different anticoagulants on multiple electrode platelet aggregometry after clopidogrel and aspirin administration in patients undergoing coronary stent implantation: A comparison between citrate and hirudin. Platelets. 2012; Epub ahead of print.
12 Kalb ML, Potura L, Scharbert G. et al. The effect of ex vivo anticoagulants on whole blood platelet aggregation. Platelets 2009; 20: 7-11.
13 Lansky AJ, Stone GW. Periprocedural myocardial infarction: prevalence, prognosis, and prevention. Circ Cardiovasc Interv 2010; 3: 602-610.
14 Mangiacapra F, Patti G, Barbato E. et al. A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome Validation Effort) study. JACC 2012; 5: 281-289.
15 Bonello L, Tantry US, Marcucci R. et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.