Regular Article
Baseline platelet size is increased in patients with acute coronary syndromes developing early stent thrombosis and predicts future residual platelet reactivity. A case-control study

https://doi.org/10.1016/j.thromres.2009.09.003Get rights and content

Abstract

Introduction

Pre-procedural predictors of early stent thrombosis (ST) and future response to platelet inhibitors are in demand. We sought to evaluate the impact of baseline platelet indices on the occurrence of early ST and future residual platelet reactivity.

Materials and methods

Hundred and eight patients with acute coronary syndromes (ACS) in whom stents were implanted were included: 36 consecutive ST cases and 72 matched controls. Platelet indices assessed with flow cytometry before stent implantation were retrieved from the department's data base. Residual platelet reactivity specific to aspirin (aspirin reaction units–ARU) and clopidogrel (P2Y12 reaction units–PRU) was assessed prospectively with VerifyNow® under dual antiplatelet treatment.

Results

Platelet size reported as mean platelet volume (MPV) or proportion of large platelets (LPLT) was significantly higher in ST cases compared with controls (10.4, 95% confidence intervals [CI], 10.1-10.8 vs. 9.7, CI, 9.5-9.9, P = 0.0004 and 35.8, CI, 34.2-37.3 vs. 33.3, CI, 32.2-34.3, P = 0.007, respectively). Dual aspirin and clopidogrel poor-responsiveness was diagnosed significantly more often in ST cases than in controls (19.6% vs. 1.4%, P = 0.004), whereas no difference was observed for single aspirin or clopidogrel poor-responsiveness. A strong correlation was found between MPV and both, ARU (r = 0.66, P < 0.0001) and PRU (r = 0.55, P < 0.0001). Similarly, higher LPLT was associated with higher ARU (r = 0.47, P < 0.0001) and PRU (r = 0.38, P = 0.0001).

Conclusions

Baseline platelet size is increased in patients with ACS developing early ST and correlates with future residual platelet reactivity under aspirin and clopidogrel therapy. Dual but not isolated aspirin or clopidogrel poor-responsiveness appears to be associated with early ST.

Introduction

Introduction of coronary stents significantly reduced the incidence of acute vessel closure and restenosis as compared to balloon angioplasty only [1], [2]. Unfortunately, initially this progress was overshadowed by unacceptably high rates of stent thrombosis (ST). In the next years, with the development of newer and more efficient antiplatelet regimens the frequency of ST was gradually decreasing. Nevertheless, despite standard dual antiplatelet therapy with aspirin and clopidogrel, ST still remains a serious and often fatal complication of percutaneous coronary interventions (PCI) [3], [4]. Early ST, constituting the vast majority of all ST, occurs during the first 30 days after stenting mainly in acute coronary syndromes (ACS) in about 1 to 2% patients with similar frequency and pattern irrespective of stent type used - bare metal or drug-eluting [5], [6]. Lately, several clinical and angiographic predictors of early ST have been identified [5]. It has also been suggested that patients with early ST incompletely respond to antiplatelet therapy [7], [8], [9], [10]. Despite extensive research early, pre-procedural factors predisposing for ST are in demand. The purpose of this study was to test if routine baseline platelet indices measured before stent implantation in ACS can predict early ST and future response to antiplatelet therapy.

Section snippets

Study population

From January 2003 to December 2007 inclusive, 2395 patients underwent PCI with bare metal stent(s) implantation due to ACS (myocardial infarction or unstable angina). Loading doses of aspirin and clopidogrel were administered before PCI. All patients were loaded with 300 mg of oral aspirin and maintained on 75 mg daily lifelong. From 2003 until mid 2006 clopidogrel was given as 300 mg loading dose, thereafter loading dose was increased to 600 mg. In both periods maintenance dose of clopidogrel was

Population characteristics

Demographics, clinical and procedural characteristics are presented in Table 1. ST cases and controls were well matched according to age, gender, clinical history and procedural technique. There was a relatively high frequency of diabetes in both groups and in the majority of patients the reason for stent implantation was non-ST segment elevation myocardial infarction. Post-stenting myocardial blush grade tended to be lower in ST cases as compared with controls (P = 0.066). (Table 1).

Baseline platelet size and early ST

Baseline PLT

Discussion

Platelets undergo activation and subsequently aggregate to form a thrombus when the intact surface of the vascular endothelium becomes disrupted [11]. This situation is present in the setting of ACS or after elective stent implantation in stable coronary artery disease. This may partly explain why PCI with stent implantation in ACS, by combining those two elements accounts for as many as nearly 90% of all early ST cases [4]. Despite continuous development in the field of antiplatelet inhibitors

Conflict of interest statement

The authors declare no conflict of interest.

Acknowledgements

This study was supported by unrestricted grant from the Polish Ministry of Science and Higher Education (N N402 4400 33).

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