Elsevier

Thrombosis Research

Volume 160, December 2017, Pages 114-118
Thrombosis Research

Full Length Article
Over-expression of cyclooxygenase-2 in increased reticulated platelets leads to aspirin resistance after elective off-pump coronary artery bypass surgery

https://doi.org/10.1016/j.thromres.2017.11.003Get rights and content

Highlights

  • Aspirin resistance (AR) occurs in 53.3% patients after OPCAB.

  • Post-OPCAB AR occurs within 3 days and vanishes within 7 days after OPCAB.

  • The surgical bleeding and COX-2 over-expression are risk factors of post-OPCAB AR.

Abstract

Introduction

Aspirin resistance (AR) has been reported to present after coronary artery bypass graft causing saphenous vein graft failure. We aimed to investigate the factors that affect the anti-platelet effect of aspirin after off-pump coronary artery bypass surgery (OPCAB).

Materials and methods

Thirty OPCAB candidates were successively recruited. Platelet count, platelet aggregation, reticulated platelet (RP), platelets' cyclooxygenase (COX)-1 and COX-2 expressions were determined during the peri-operative period. Besides, 10 healthy volunteers were enrolled to determine the onset of the anti-platelet effect of aspirin as comparison.

Results and conclusions

The arachidonic acid-induced platelet aggregation (PLAA) decreased to < 20% within 8 h after taking 100 mg aspirin in healthy volunteers. However, in the OPCAB patients, PLAA levels remained over 20% in 16 (53.3%) patients after resuming aspirin for 24 h. The surgical bleeding volumes were higher in the AR patients compared to the normal responders (512.5 ± 192.8 vs. 314.3 ± 94.9, p = 0.002). The platelet count on Day 8, RP proportions on Days 1, 4, 8, and COX-2 level on Day 4 were significantly increased compared to their baseline levels in AR group but not in AS group. Platelet count on Day 8, RP proportion and COX-2 on Day 4 were all significantly higher in AR group than those in AS group. The surgical bleeding volume and COX-2 over-expression were predictors of post-OPCAB AR. As a conclusion, the inability of aspirin to inhibit the COX-2 created by increased RP would account for the post-OPCAB AR.

Introduction

Our previous study revealed that there were 50% patients who presented with aspirin resistance (AR) after orthopedic surgery [1], in which we supposed that the accelerated platelet turnover during the post-operative period might be a possible cause of the phenomenon. Other studies showed that low aspirin response also presents after either on-pump or off-pump coronary artery bypass grafting (CABG), which may lead to saphenous vein graft occlusion or even cardiac death [2], [3]. The mechanism of the post-CABG AR has not yet been identified [4], [5], [6]. This study aimed to include the off-pump CABG (OPCAB) patients who may experience less platelet turnover, and investigate the incidence of post-operative AR and its mechanism.

Section snippets

Study population

A total of 30 coronary artery disease (CAD) patients diagnosed by coronary arteriography (CAG) and intended to receive elective OPCAB were continuously recruited in the First Affiliated Hospital, Nanjing Medical University. The patients were required to withdraw aspirin and clopidogrel for at least 7 days before surgery and resume aspirin 100 mg (Enteric Coated Tablets, Bayer HealthCare AG, Germany) once daily after surgery as soon as possible. Aspirin was administered to every subject at 8:00 

Platelet function test, presence of post-operative AR, and comparisons between AR and aspirin sensitive (AS) patients

Levels of PLAA in 10 healthy volunteers all declined to < 20% within 8 h after taking 100 mg aspirin. Accordingly, we defined AR on the basis of PLAA levels over 20% at 24 h after resuming 100 mg aspirin. As a result, 16 (53.3%) patients presented post-OPCAB AR. However, the incidence of AR diminished by time, and vanished within a week after OPCAB (Fig. 1). LTA aggregation curves are shown in Appendix 1(A and B).

Based on the PLAA results, the patients were divided into AR group (n = 16) and AS group (

Discussion

This study demonstrated that aspirin resistance (AR) occurred in 53.3% patients after elective OPCAB; post-OPCAB AR occurred within 3 days and vanished within 7 days after elective OPCAB; the surgical bleeding and over-expression of COX-2 were two risk factors that significantly associated with the post-OPCAB AR.

With confounding factors including demographic characteristics, risk factors of CAD and surgical variables considered, we found significantly more intra-operative bleeding and higher

Conflict of interest statement

None.

Acknowledgments

This work was supported by a grant from the New Investigator Fund of Hamilton Health Sciences Corporation, Hamilton, Canada [NIF-08200(R)], a grant from the Jiangsu Province's Key Provincial Talents Program (ZDRCA2016013), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD).

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These authors contributed equally to this study.

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