Abstract
Objective
The Japanese Circulation Society recommends discontinuation of antiplatelet therapy 7–14 days before major surgery. However, reports on the relationship between the timing of clopidogrel discontinuation and the risk of postoperative bleeding in Japanese subjects are lacking. We assessed the optimal timing of clopidogrel discontinuation before elective surgery using the VerifyNow® P2Y12 assay. In addition, the relationship between preoperative platelet function and risk of postoperative bleeding was evaluated.
Methods
Study 1: Between June 2012 and December 2014, Platelet function was examined by the VerifyNow P2Y12 assay in patients scheduled for cardiac surgery, every other day after clopidogrel cessation. Study 2: We compared the preoperative platelet function, measured by the VerifyNow, with the postoperative bleeding.
Results
Study 1: Twenty-four patients were included in this study. The mean P2Y12 reaction units (PRU) on Day-0 was 186, and increased significantly to 283 PRU on Day-7 in a time-dependent manner after clopidogrel discontinuation (p = 0.001). The mean PRU value significantly exceeded the cutoff of 230 on Day-5. Study 2: Correlation between the preoperative aspirin reaction units (ARU) and postoperative bleeding showed a slight inverse correlation in patients undergoing aortic valve replacement (rS = −0.363, p = 0.013), mitral valve plasty (rS = −0.300, p = 0.085) and off-pump coronary artery bypass (rS = −0.176, p = not significant).
Conclusion
Platelet aggregation had already recovered at 5 days after clopidogrel cessation. Surgeons could consider decreasing the interval from clopidogrel discontinuation to surgery from the recommended 7–14 days. The VerifyNow assay can be used to predict the risk of perioperative bleeding.
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References
Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: executive summary. J Am Coll Cardiol. 2011;58:2584–614.
Kapetanakis EI, Medlam DA, Boyce SW, Haile E, Hill PC, Dullum MK, et al. Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist’s panacea or the surgeon’s headache? Eur Heart J. 2005;26:576–83.
Fox KA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial. Circulation. 2004;110:1202–8.
Leong JY, Baker RA, Shah PJ, Cherian VK, Knight JL. Clopidogrel and bleeding after coronary artery bypass graft surgery. Ann Thorac Surg. 2005;80:928–33.
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.
Grujic D, Martin D. Perioperative clopidogrel is seven days enough? Am Surgeon. 2009;75:909–13.
Malinin A, Pokov A, Swaim L, Kotob M, Serebruany V. Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel. Methods Find Exp Clin Pharmacol. 2006;28:315–22.
Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJT, Bal ET, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA J Am Med Assoc. 2010;303:754–62.
Malinin A, Pokov A, Spergling M, Defranco A, Schwartz K, Schwartz D, et al. Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study. Thromb Res. 2007;119:277–84.
Paniccia R, Antonucci E, Gori AM, Marcucci R, Giglioli C, Antoniucci D, et al. Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients. J Thromb Haemost. 2007;5:1839–47.
van Werkum JW, van der Stelt CAK, Seesing TH, Hackeng CM, ten Berg JM. A head-to-head comparison between the VerifyNow (R) P2Y12 assay and light transmittance aggregometry for monitoring the individual platelet response to clopidogrel in patients undergoing elective percutaneous coronary intervention. J Thromb Haemost. 2006;4:2516–8.
Guidelines for management of anticoagulant and antiplatelet therapy in cardiovascular disease (JCS). 2009.
Reed G, Hoffman E, Kumar A, Maree A, McLean D, Buros J, et al. Platelet function testing predicts bleeding in patients exposed to clopidogrel undergoing coronary artery bypass grafting. J Am Coll Cardiol. 2012;60:B210–1.
Acknowledgments
We gratefully acknowledge the participants and supporting staff for enabling us to conduct this study. This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan and the project study of Kawasaki Medical School from 2012 to 2015.
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Takiuchi, H., Tanemoto, K. Optimal timing of clopidogrel discontinuation in Japanese patients: platelet aggregation test using the VerifyNow® system. Gen Thorac Cardiovasc Surg 63, 601–606 (2015). https://doi.org/10.1007/s11748-015-0583-2
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DOI: https://doi.org/10.1007/s11748-015-0583-2