Point-of-care platelet function testing predicts bleeding in patients exposed to clopidogrel undergoing coronary artery bypass grafting: Verify pre-op TIMI 45--a pilot study

Abstract

Background: Guidelines recommend delaying coronary artery bypass grafting (CABG) for 5 days after discontinuing clopidogrel. However, platelet function may recover quicker in certain individuals.

Hypothesis: We hypothesized that perioperative measurement of platelet function with a point-of-care P2Y12 inhibitor assay could predict bleeding during CABG in patients exposed to clopidogrel.

Methods: Verify Pre-Op TIMI 45 was a prospective pilot study of 39 patients on clopidogrel who subsequently underwent CABG. Preoperative on-treatment platelet reactivity was assessed with VerifyNow P2Y12 Reaction Units (PRU), with higher PRU indicating more reactive platelets. Outcomes were stratified by PRU quartiles, as well as prespecified cutpoints for the lowest quartile (PRU 173), a cutpoint for major bleeding determined by the Youden index using receiver operator curve analysis (PRU 207), and clopidogrel resistance (PRU 230).

Results: Patients in higher PRU quartiles experienced smaller decreases in hemoglobin and hematocrit (P < 0.05 for all comparisons), less major bleeding (P = 0.021), and less major or minor bleeding (P = 0.003). Patients above the PRU 207 and 230 cutpoints had less chest-tube output (P = 0.041 and P = 0.012, respectively), less major bleeding (P = 0.005 and P = 0.036, respectively), and less major or minor bleeding (P = 0.013 and P < 0.001, respectively). By receiver operator curve analysis, preoperative PRU ≤ 207 discriminated between patients with and without major bleeding during surgery (area under the curve: 0.76, 95% confidence interval: 0.59-0.94, P = 0.018).

Conclusions: In this pilot study, we found that point-of-care platelet function assessment could predict bleeding in patients recently exposed to clopidogrel undergoing CABG.

Figure 1

Bleeding outcomes specified by PRU quartiles. Values are depicted as percentage of group total with absolute number of patients in parentheses. * indicates statistical significance at P = 0.021; † indicates statistical significance at P = 0.0003. Abbreviations: PRU, P2Y₁₂ Reaction Units; Q, quartile.

Figure 2

Bleeding outcomes stratified by PRU cutpoints. Values are depicted as percentage of group total with absolute number of patients underneath. * indicates statistical significance at P < 0.05; † indicates statistical significance at P < 0.001. Abbreviations: PRU, P2Y₁₂ Reaction Units.