Immature platelet fraction and high-on treatment platelet reactivity with ticagrelor in patients with acute coronary syndromes

Abstract

Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2-9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100-160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5-3.99; ≥4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = -0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34-1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30-90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR.

Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor

“…For the nonthienopyridine and also reversibly acting substance ticagrelor, similar results of a missing interaction have been previously reported. 15,35,36 These findings for ticagrelor were confirmed in our study. At day 1 following cangrelor infusion, the clopidogrel and prasugrel group showed the expected correlation of levels of reticulated platelet and platelet reactivity, whereas this association was not seen in the ticagrelor group.…”

“…14 For the reversible P2Y 12 -receptor inhibitor ticagrelor, no association of reticulated platelets and antiplatelet response could be demonstrated. 15,16 Recently, the first intravenous, reversible P2Y 12 -receptor inhibitor cangrelor was approved for peri-interventional therapy. 17,18 This drug provides an almost immediate and complete inhibition of ADP-induced platelet aggregation, 18,19 and has a rapid off-set of antiplatelet effects within 1 hour following discontinuation.…”

Impact of active smoking on the immature platelet fraction and its relationship with the extent of coronary artery disease

“…52 Indeed, immature platelets have been previously hypothesized playing a role in the prediction of atherosclerosis, 39 but its role especially in acute settings is not clear whether enhanced platelet turnover is the cause or the consequence of the acute atherothrombotic event. However, contrasting results have been found relating reticulated platelets to an impaired response to antiplatelet agents, 38,[55][56][57] implying further studies to assess the clinical significance of immature platelet on clinical settings. In fact, no significant impact of higher IPF values has been detected on prediction in the presence of CAD at angiography, after correction for main baselines differences.…”

“…54 Raising attention has been focused on potential impact of immature platelet on response to antiplatelet drugs. However, contrasting results have been found relating reticulated platelets to an impaired response to antiplatelet agents, 38,[55][56][57] implying further studies to assess the clinical significance of immature platelet on clinical settings. IPF then would represent a marker of platelet turnover rather than being directly involved in the pathogenesis of cardiovascular disease.…”

Impact of diabetes mellitus on immature platelet fraction and its association with coronary artery disease

“…Blood cells count was performed in a blood sample collected in tripotassium ethylenediaminetetraacetic acid (EDTA) (7.2 mg) tubes and analysed within 2 hours from drawing by an automatic blood cells counter (A Sysmex XE‐2100). The percentage of RPs was defined as the percentage of immature platelets within the total platelet count or IPF, determined by a fully automated sorting system (forward light scatter vs fluorescence scatterplot) of the Sysmex XE‐2100 instrument, as previously described . The expected coefficient of variation (CV) was less than or equal to 20% according to the manufacturer.…”