Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery

Petričević, Mate; Miličić, Davor; White, Alexandra; Boban, Marko; Mihaljević, Martina Zrno; Piljić, Dragan; Rotim, Ante; Buča, Ante; Mihalj, Mario; Biočina, Bojan

doi:10.1007/s11239-015-1246-y

Cited by 17 publications

(5 citation statements)

References 33 publications

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“…To stimulate the aggregation, multiple agonists can be used to test different platelet activation pathways. An attempt has been made to determine a therapeutic window for APT dosage based on the Multiplate results in patients with coronary artery disease [37]. However, measuring platelet function by global aggregation measure approach is usually less specific to evaluate the effect of specific antiplatelet drug.…”

Section: Discussionmentioning

confidence: 99%

The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays

et al. 2016

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Patients on P2Y inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y inhibition on platelet function in vivo. Therefore, we investigated whether measuring platelet reactivity toward other physiologically relevant agonists could provide more insight in the efficacy of P2Y inhibitors. The effect of in vitro and in vivo P2Y inhibition on αIIbβ3-activation, P-selectin and CD63-expression, aggregate formation, release of alpha, and dense granules content was assessed after stimulation of different platelet activation pathways. Platelet reactivity measured with flow cytometry in 72 patients on P2Y inhibitors was compared to VerifyNow results. P2Y inhibitors caused strongly attenuated platelet fibrinogen binding after stimulation with peptide agonists for protease activated receptor (PAR)-1 and -4, or glycoprotein VI ligand crosslinked collagen-related peptide (CRP-xl), while aggregation was normal at high agonist concentration. P2Y inhibitors decreased PAR-agonist and CRP-induced dense granule secretion, but not alpha granule secretion. A proportion of P2Y-inhibitor responsive patients according to VerifyNow, displayed normal fibrinogen binding assessed with flow cytometry after stimulation with PAR-agonists or CRP despite full inhibition of the response to ADP, indicating suboptimal platelet inhibition. Concluding, measurement of platelet fibrinogen binding with flow cytometry after stimulation of thrombin- or collagen receptors in addition to ADP response identifies different patients as nonresponders to P2Y inhibitors, compared to only ADP-induced aggregation-based assays. Future studies should investigate the value of both assays for monitoring on-treatment platelet reactivity.

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Section: Discussionmentioning

confidence: 99%

The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays

et al. 2016

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“…Pre-operative platelet function testing can be used to detect a residual platelet function defect in patients treated with antiplatelet drugs or other drugs that might impair platelet function in order to reduce the waiting time until surgery after cessation of ADP-receptor antagonists [78][79][80][81][82]. However, the intra-and post-operative changes in platelet function seem to be more significant and important for peri-operative bleeding management in patients undergoing cardiac surgery with CPB [47,60,[82][83][84][85]. Accordingly, platelet function testing results achieved after protamine administration demonstrated the best correlation with postoperative chest tube drainage and postoperative transfusion requirements that were dependent on the degree of platelet inhibition and the number of pathways inhibited [47].…”

Section: Korean J Anesthesiolmentioning

confidence: 99%

The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

Görlinger

Pérez-Ferrer

Dirkmann

et al. 2019

Korean J Anesthesiol

163

138

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Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management ('theranostic' approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient's safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration. Fig. 1. ROTEM trace ('temogram') displaying the clinically most important parameters and their informative value. FDPs: fibrin (ogen) split products. Courtesy of Klaus Görlinger, Germany.

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“…19 Petricevic et al also tried to define a therapeutic window for aspirin using aggregometry and reported that the lowest AA value to avoid bleeding was 20 U. 20 Our study showed that an AA value of 16.5 U exhibited an 83.3% specificity and a 50.8% sensitivity. Thus, our cutoff value is similar to those of previous reports.…”

Section: Discussionmentioning

confidence: 49%

Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty After Tooth Extraction in Patients Receiving Antiplatelet Therapy

Nagao

Masuda

Ando

et al. 2017

Clin Appl Thromb Hemost

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When patients on antiplatelet therapy (APT) require minor invasive surgery, APT is usually continued to limit the risk of thrombosis. However, the possibility of hemostatic difficulties necessitates the monitoring of platelet aggregation to prevent unexpected bleeding. We examined whether whole blood aggregometry as a point-of-care testing (POCT) could be useful as a tool for predicting hemostatic difficulties. Sixty-five patients receiving APT and 15 patients who were not receiving APT were enrolled in the present study; all patients were scheduled to undergo a tooth extraction. Whole blood samples were obtained and were examined using multiple electrode aggregometry. The aggregometry was performed using arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor activating peptide. Hemostatic difficulty was defined as a need for more than 10 minutes of compression to achieve hemostasis. The AA test results were significantly lower in patients treated with aspirin (control: 97.7 [29.0] U, aspirin: 14.5 [7.2] U, P < .001). The ADP test results were also significantly lower in patients treated with a P2Y inhibitor (control: 77.7 [21.7] U, P2Y inhibitor: 37.3 [20.4] U, P < .01). Six of the examined cases exhibited hemostatic difficulties. The cutoff values for the prediction of hemostatic difficulty were 16.5 U for the AA test (sensitivity, 0.833; specificity, 0.508) and 21 U for the ADP test (sensitivity, 0.847; specificity, 0.500). Our study showed that whole blood aggregometry was useful as a POCT for the prediction of hemostatic difficulties after tooth extraction in patients receiving APT.

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Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery

Cited by 17 publications

References 33 publications

The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays

The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays

The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty After Tooth Extraction in Patients Receiving Antiplatelet Therapy

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