Multiple Electrode Whole-Blood Aggregometry and Bleeding in Cardiac Surgery Patients Receiving Thienopyridines

Department of Cardiothoracic-Vascular Anesthesia and Intensive Care, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Donato, Milan, Italy.
The Annals of thoracic surgery (Impact Factor: 3.45). 01/2011; 91(1):123-9. DOI: 10.1016/j.athoracsur.2010.09.022
Source: PubMed

ABSTRACT Preoperative treatment with thienopyridines is associated with increased postoperative bleeding in cardiac surgery patients. Patients under treatment with thienopyridines have different levels of platelet dysfunction and the effects of discontinuation are not totally predictable. The present study aimed to determine if a preoperative assessment of platelet function in these patients could provide clinically relevant information regarding the risks of excessive postoperative bleeding and transfusion requirements.
This is a retrospective analysis of prospectively collected data. Patients (n=87) under thienopyridine treatment until at least one week before cardiac surgery were enrolled in the study. Platelet function was assessed preoperatively with multiple electrode aggregometry: the adenosine diphosphate (ADP) test and TRAP (thrombin receptor-associated peptide) test were performed for all patients.
Univariate analysis revealed that postoperative bleeding was associated (p<0.1) with preoperative serum creatinine level, platelet count, CPB (cardiopulmonary bypass) duration, and results from the ADP test and the TRAP test. Multivariable linear regression analysis confirmed the CPB duration (p=0.049) and ADP test (p=0.007) as independently associated with postoperative bleeding. The relationship between the ADP test and postoperative bleeding was investigated with polynomial regression analysis, and a logarithmic equation provided the best fit. The accuracy of prediction was good (area under the curve 0.71, p=0.013), with a cutoff value for the ADP test at 31 U (sensitivity 72%, specificity 66%, negative predictive value 92%, and positive predictive value 29%).
The multiple electrode aggregometry ADP test in patients under thienopyridine treatment and undergoing cardiac surgery is associated with postoperative bleeding and platelet transfusion and provides an accurate preoperative prediction of postoperative bleeding risk.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Drugs that act on the platelet P2Y12 receptor are responsible for postoperative bleeding in cardiac surgery. However, protease-activated receptor (PAR) that reacts to thrombin stimulation might still be active in patients treated with P2Y12 inhibitors. Preoperative platelet function testing could possibly guide the timing of surgery. We investigated the association between P2Y12 receptor and PAR inhibition and bleeding after cardiac surgery. Methods. A retrospective cohort study of 361 patients undergoing cardiac surgery and treated with P2Y12 anti-platelet agents was undertaken. All patients received a preoperative multiplate electrode aggregometry testing of platelet P2Y12 receptor activity (ADPtest) and PAR reactivity with thrombin receptor-activating peptide (TRAP) stimulation. ADPtest and TRAPtest data measured before surgery were analysed for association with postoperative bleeding (ml per 12 h) and severe postoperative bleeding. Results. Both the ADPtest and the TRAPtest were significantly (P=0.001) associated with postoperative bleeding. A threshold of 22 U for the ADPtest yielded a negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 20%, and a threshold of 75 U for the TRAPtest yielded an NPV of 95% and a PPV of 23%. In the subgroup of patients with ADPtest <22 U, TRAPtest >= 75 U was not associated with severe bleeding (NPV of 100% and PPV of 37%). Conclusions. In patients taking P2Y12 receptor inhibitors, residual platelet reactivity to thrombin stimulation limits the risk of severe postoperative bleeding.
    BJA British Journal of Anaesthesia 09/2014; 113(6). DOI:10.1093/bja/aeu315 · 4.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation - adhesion, shape change, release reaction, and aggregation - have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered.
    Vascular Health and Risk Management 01/2015; 11:133. DOI:10.2147/VHRM.S44469
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Patients often fail to stop clopidogrel appropriately before non-cardiac surgery. Thromboelastography platelet mapping (TEG-PM) can be used to measure the percentage adenosine 5′-diphosphate platelet receptor inhibition (ADP-PRI) by clopidogrel in these patients.Methods This prospective case–control study investigated the risk of bleeding in patients who had taken clopidogrel within 7 days of scheduled operation. Patients underwent TEG-PM to stratify their bleeding risk. Low-risk (ADP-PRI below 30 per cent) and urgent priority high-risk (ADP-PRI 30 per cent or more) patients proceeded to surgery. The outcomes of these patients were compared with those of matched controls. Regression analysis, with bootstrapping validation, was used to identify independent risk factors for bleeding and an optimal cut-off value of ADP-PRI for cancellation of surgery.ResultsFrom May 2008 to October 2013, 182 patients failed to discontinue clopidogrel. No correlation was observed between duration of clopidogrel omission and percentage ADP-PRI; 112 low-risk and 19 high-risk patients proceeded to surgery. High-risk patients had significantly greater intraoperative packed red blood cell (PRBC) transfusion in comparison with their matched controls, and a strong positive correlation between percentage ADP-PRI and units of intraoperative PRBCs transfused (r = 0·749, 95 per cent confidence interval (c.i.) 0·410 to 0·940; P < 0·001). Percentage ADP-PRI was the only independent risk factor for intraoperative PRBC transfusion (odds ratio 1·07, 95 per cent c.i. 1·02 to 1·13; P = 0·005).Conclusion An objective measure of platelet inhibition with TEG-PM, using an ADP-PRI cut-off of 34 per cent, can be used to prevent unnecessary cancellations, while minimizing patient risk.
    British Journal of Surgery 07/2014; 101(11). DOI:10.1002/bjs.9592 · 4.84 Impact Factor


Available from
May 26, 2014