Full Length ArticleOver-expression of cyclooxygenase-2 in increased reticulated platelets leads to aspirin resistance after elective off-pump coronary artery bypass surgery
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).
References (18)
- et al.
Aspirin response variability after major orthopedic surgery
Thromb. Res.
(2012 Aug) - et al.
Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after coronary artery bypass graft surgery
J. Am. Coll. Cardiol.
(2011 Mar 1) - et al.
Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin
J. Thromb. Haemost.
(2007 Mar) - et al.
Assessing aspirin-induced attenuation of platelet reactivity by flow cytometry
Thromb. Res.
(2007) - et al.
Once versus twice daily aspirin after coronary bypass surgery: a randomized trial
J. Thromb. Haemost.
(2017 May) - et al.
Multiple daily doses of acetyl-salicylic acid (ASA) overcome reduced platelet response to once-daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial
J. Thromb. Haemost.
(2015 Mar) - et al.
Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease
J. Am. Coll. Cardiol.
(2008 Aug 26) - et al.
Results of a worldwide survey on the assessment of platelet function by light transmission aggregometry: a report from the platelet physiology subcommittee of the SSC of the ISTH
J. Thromb. Haemost.
(2009 Jun) - et al.
Low platelet activity predicts 30 days mortality in patients undergoing heart surgery
Blood Coagul. Fibrinolysis
(2016 Mar)
Cited by (7)
Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism – results from clinical observation studies
2020, EBioMedicineCitation Excerpt :In patients presenting with acute myocardial infarction while on chronic ASA treatment, administration of a loading dose of ASA has been related to greater reduction of platelet thromboxane synthesis [30]. Uninhibited cyclooxygenase (COX)-2 due to increased platelet production and release of new reticulated platelets is another proposed mechanism in the case of myeloproliferative neoplasm patients and in perioperative patients at risk for thrombosis [31,32]. Despite the lower platelet count and lower MPV in VTE individuals compared to those without VTE, increased platelet production and turnover could not be excluded in the acute phase of the disease.
The Relationship Between Aspirin Resistance and Carotid Imaging in Young Patients With ST-Segment Elevated Myocardial Infarction: A Cross-Sectional Study
2018, Clinical and Applied Thrombosis/HemostasisThe Development of an In Vitro Assay for the Prospective Determination of Aspirin Sensitivity
2018, Journal of Clinical Pharmacology
- 1
These authors contributed equally to this study.