Association among Clopidogrel Cessation, Platelet Function, and Bleeding in Coronary Bypass Surgery: An Observational Trial

Abstract

Objectives This study sought to determine (1) the association between the length of preoperative clopidogrel discontinuation, blood loss, and transfusion requirements and (2) whether preoperative platelet function testing predicts excessive postoperative bleeding in patients undergoing coronary artery bypass grafting (CABG) surgery.

Methods In this retrospective analysis, patients undergoing CABG were divided into three groups with regard to the period between preoperative clopidogrel cessation and surgery: group 1 (n = 94, ≤3 days), group 2 (n = 100, 4–5 days), and group 3 (n = 83, 6–7 days), respectively. Impedance aggregometry (Multiplate) with arachidonic acid (ASPI) test assay (used for platelets stimulation) and adenosine diphosphate (ADP) test (used for platelets stimulation) was performed before the surgery. Primary outcome was 24 hours chest tube output (CTO) and transfusion requirements (red blood cell concentrate [RBCC], platelet concentrate [PC], fibrinogen concentrate [FC], and fresh-frozen plasma [FFP]) were considered as secondary outcomes.

Results CTO during 24 hours was significantly higher in group 1 as compared with groups 2 and 3, respectively (p = 0.003). Considering secondary outcomes, RBCC (p = 0.043), PC (p = 0.001), FC (p = 0.003), and FFP (p = 0.010) were more frequently transfused in group 1 as compared with groups 2 and 3, respectively. Multiple electrode aggregometry ASPI and ADP tests were significantly correlated with the 24-hour CTO (ASPI test—rho = −0.258, p < 0.001; ADP test—rho = −0.164, p = 0.007). A significant correlation was observed between clopidogrel-free interval and 24-hour CTO (rho = −0.200, p < 0.001). Receiver-operating characteristics (ROC) curve analysis revealed cutoff values to delineate bleeding tendency (ASPI test ≤ 25 area under the aggregation curve [AUC], ADP test ≤63 AUC, and clopidogrel-free interval ≤3 days).

Conclusion Excessive postoperative bleeding occurred less frequently if the period between clopidogrel discontinuation and surgery was longer than 3 days, as compared with shorter waiting time. Inadequate recovery of the platelets function following clopidogrel cessation in preoperative period was associated with increased bleeding risk. Platelet function testing was found to be a useful tool for postoperative bleeding management in our hands.

Keywords

coronary artery bypass grafting - multiple electrode aggregometry - antiplatelet - drugs - clopidogrel - transfusion

^* Both authors contributed equally to this work.

Publication History

Received: 05 March 2019

Accepted: 29 May 2019

Article published online:
30 July 2019

• References

• 1 Koch CG, Li L, Duncan AI. et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006; 34 (06) 1608-1616
• 2 Dixon B, Santamaria JD, Reid D. et al. The association of blood transfusion with mortality after cardiac surgery: cause or confounding? (CME). Transfusion 2013; 53 (01) 19-27
• 3 Siller-Matula JM, Petre A, Delle-Karth G. et al. Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in cardiac and non-cardiac surgery: a systematic review and meta-analysis. Eur Heart J Acute Cardiovasc Care 2017; 6 (08) 753-770
• 4 Morici N, Moja L, Rosato V. et al. Time from adenosine di-phosphate receptor antagonist discontinuation to coronary bypass surgery in patients with acute coronary syndrome: meta-analysis and meta-regression. Int J Cardiol 2013; 168 (03) 1955-1964
• 5 Hansson EC, Jidéus L, Åberg B. et al. Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study. Eur Heart J 2016; 37 (02) 189-197
• 6 Mahla E, Suarez TA, Bliden KP. et al. Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graft surgery: the timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study. Circ Cardiovasc Interv 2012; 5 (02) 261-269
• 7 Yu PJ, Cassiere HA, Dellis SL, Manetta F, Stein J, Hartman AR. P2Y12 platelet function assay for assessment of bleeding risk in coronary artery bypass grafting. J Card Surg 2014; 29 (03) 312-316
• 8 Samardzic J, Krpan M, Skoric B, Pasalic M, Petricevic M, Milicic D. Serial clopidogrel dose adjustment after platelet function testing improves outcome of acute coronary syndrome patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity. J Thromb Thrombolysis 2014; 38 (04) 459-469
• 9 Petricevic M, Kopjar T, Biocina B. et al. The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: a systematic review. Thorac Cardiovasc Surg 2015; 63 (01) 2-20
• 10 Petricevic M, Biocina B, Milicic D. et al. Bleeding risk assessment using multiple electrode aggregometry in patients following coronary artery bypass surgery. J Thromb Thrombolysis 2013; 35 (01) 31-40
• 11 Petricevic M, Biocina B, Milicic D. et al. Bleeding risk assessment using whole blood impedance aggregometry and rotational thromboelastometry in patients following cardiac surgery. J Thromb Thrombolysis 2013; 36 (04) 514-526
• 12 Petricevic M, Konosic S, Biocina B. et al. Bleeding risk assessment in patients undergoing elective cardiac surgery using ROTEM(®) platelet and Multiplate(®) impedance aggregometry. Anaesthesia 2016; 71 (06) 636-647
• 13 Tóth O, Calatzis A, Penz S, Losonczy H, Siess W. Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood. Thromb Haemost 2006; 96 (06) 781-788
• 14 Hillis LD, Smith PK, Anderson JL. et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124 (23) 2610-2642
• 15 Ebrahimi R, Dyke C, Mehran R. et al. Outcomes following pre-operative clopidogrel administration in patients with acute coronary syndromes undergoing coronary artery bypass surgery: the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. J Am Coll Cardiol 2009; 53 (21) 1965-1972
• 16 Mehta RH, Roe MT, Mulgund J. et al. Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery. J Am Coll Cardiol 2006; 48 (02) 281-286
• 17 Klein AA, Arnold P, Bingham RM. et al. AAGBI guidelines: the use of blood components and their alternatives 2016. Anaesthesia 2016; 71 (07) 829-842
• 18 Ranucci M, Colella D, Baryshnikova E, Di Dedda U. ; Surgical and Clinical Outcome Research (SCORE) Group. Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery. Br J Anaesth 2014; 113 (06) 970-976
• 19 Pagano D, Milojevic M, Meesters MI. et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. Eur J Cardiothorac Surg 2018; 53 (01) 79-111
• 20 Meesters MI, Veerhoek D, de Lange F. et al. Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial. Thromb Haemost 2016; 116 (02) 251-261
• 21 Bedeir K, Bliden K, Tantry U, Gurbel PA, Mahla E. Timing of coronary bypass surgery in patients receiving clopidogrel: the role of VerifyNow. Can J Cardiol 2016; 32 (06) 724-725
• 22 Petricevic M, Biocina B, Milicic D, Rotim C, Boban M. Platelet function testing and prediction of bleeding in patients exposed to clopidogrel undergoing coronary artery surgery. Clin Cardiol 2015; 38 (07) 443-444