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.

The routine use of platelet function tests in elective coronary artery bypass grafting: A prospective observational trial

“…The origin of the hemostatic disturbances after cardiac surgery is multifactorial—the effect of the heart‐lung machine (CPB) on platelet function, activated coagulation cascade, heparin‐induced coagulopathy, and fibrinolysis 3 . Postoperative morbidity caused by excessive bleeding is also a consequence of higher blood transfusion rate, as well as mechanisms that are not transfusion‐related 4 …”

“…3 Postoperative morbidity caused by excessive bleeding is also a consequence of higher blood transfusion rate, as well as mechanisms that are not transfusion-related. 4 Furthermore, dual antiplatelet therapy remains the cornerstone of therapy in these patients. There is clear evidence that clopidogrel, ticagrelor, and prasugrel should be discontinued 3, 5, and 7 days before surgery, respectively, so as to prevent perioperative complications caused by coagulation disorders, while aspirin is recommended to be continued until the day of surgery.…”

Bleeding Risk Stratification in Coronary Artery Surgery the Should-Not-Bleed Score

“…Apparently, there was no need to put in the app whether someone was exposed to Aspirin preoperatively. However, our research group previously con rmed the presence of subset of patients who have prolonged and pronounced platelet inhibitory response to Aspirin (16) , which in turn re ects bleeding tendency. We showed recently that patients with adequate platelet inhibitory response to Aspirin are prone to excessive bleeding (16).…”

“…However, our research group previously con rmed the presence of subset of patients who have prolonged and pronounced platelet inhibitory response to Aspirin (16) , which in turn re ects bleeding tendency. We showed recently that patients with adequate platelet inhibitory response to Aspirin are prone to excessive bleeding (16). Multiplate ASPI test AUC <25 U was found to be predictive of excessive bleeding (OR 2.82 [95% CI 1.43-5.55], p=0.003) which generates the idea about the subset of patients who have pronounced platelet inhibition on Aspirin therapy and who could bene t from preoperative aspirin cessation (16).…”

“…We showed recently that patients with adequate platelet inhibitory response to Aspirin are prone to excessive bleeding (16). Multiplate ASPI test AUC <25 U was found to be predictive of excessive bleeding (OR 2.82 [95% CI 1.43-5.55], p=0.003) which generates the idea about the subset of patients who have pronounced platelet inhibition on Aspirin therapy and who could bene t from preoperative aspirin cessation (16). The mathematical risk modelling used as a platform for SHOULD-NOT-BLEED risk score has also proved Multiplate ASPI test value as an independent predictor of bleeding (5).…”