Platelet turnover predicts outcome after coronary intervention.

Thomas Weiss,Martin Willheim,Miklos Rohla,Johann Wojta,Kurt Huber,Florian Egger,Wolfgang Hübl,Veronika Bruno,Liana Iliev,Matthias Freynhofer

doi:10.1160/th16-10-0785

Abstract

SummaryElevated platelet turnover contributes to high platelet reactivity. High platelet reactivity after percutaneous coronary intervention (PCI) is associated with major adverse cardiovascular events (MACE). The purpose of this study was to determine the prognostic value of platelet turnover and function with regard to MACE after PCI with stent implantation. In this prospective observational study, 486 consecutive patients after PCI on aspirin and clopidogrel were included to determine platelet turnover (mean platelet volume (MPV), reticulated platelet fraction (RPF)) and platelet function (multiple electrode aggregometry (MEA), vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay). At six-months follow-up, MACE occurred in 10.7 % of patients. RPF (odds ratio [OR]=1.173 (95% confidence interval [CI 95 %] 1.040–1.324), p=0.009) and MPV (OR=1.459 (CI 95 % 1.059–2.008), p=0.021) were univariable predictors of MACE, whereas VASP-P (OR=1.016 (CI 95 % 1.000–1.032), p=0.052) and MEA (OR=0.999 (CI 95 % 0.980–1.017), p=0.895) failed to predict MACE. RPF remained the only platelet variable independently associated with MACE. The best model to predict MACE included: troponin I (OR=1.007 (CI 95 % 1.002–1.012), p=0.009), RPF (OR=1.136 (CI 95 % 1.001–1.288), p=0.048), CRP (OR=1.008 (CI 95 % 1.001–1.014), p=0.023) and history of myocardial infarction (OR=2.039 (CI 95 % 1.093–3.806), p=0.025). RPF (OR=1.211 (CI 95 % 1.042–1.406), p=0.012) was also independently associated with in-hospital bleedings. In conclusion, RPF as index of platelet turnover is an independent predictor of MACE and bleeding events in PCI patients on dual antiplatelet therapy. Since RPF can reliably be quantified along with routine haemograms, RPF might easily be applied in the setting of cardiovascular risk prediction.

Highlights

Platelets are a pivotal element in primary haemostasis and repair of endothelial damage
The most important finding of the present investigation is that reticulated platelet fraction (RPF) as index of platelet turnover is an independent predictor of major adverse cardiovascular events (MACE) in patients undergoing percutaneous coronary intervention (PCI) with stenting on dual antiplatelet therapy with aspirin and clopidogrel
Studies have found that increased megakaryocyte ploidy is present in patients with atherosclerosis, myocardial infarction as well as in patients with sudden cardiac death and that it is inversely correlated with bleeding time [24,25,26]

Summary

Introduction

Platelets are a pivotal element in primary haemostasis and repair of endothelial damage. Platelets are essentially involved in initiation and propagation of atherosclerosis and acute coronary syndromes [1]. E. high on- (clopidogrel-) treatment platelet reactivity (HTPR), has been linked to adverse ischaemic outcome in numerous investigations and vice versa, good response to clopidogrel might be associated with increased risk of bleeding [5]. Larger platelets are younger and more reactive compared to their counterparts [6,7,8]. In situations with enhanced platelet turnover with release of new platelets from the bone marrow, the fraction of larger, and more reactive platelets increases. There is evidence that MPV predicts myocardial infarction, death after myocardial infarction or restenosis following PCI [9], and the megakaryocyteplatelet system might even be causally involved in the initiation or propagation of atherosclerosis and acute coronary syndromes (ACS) [10].

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