Circulating reticulated platelets over time in patients with myocardial infarction treated with prasugrel or ticagrelor

Abstract

Reticulated platelets (RP) are young, hyperactive platelets that are increased during situations of enhanced platelet turnover such as acute myocardial infarction (AMI). The dynamics of RP levels after AMI is not established. We aimed to characterize the levels of circulating RP over time in patients with AMI. Patients with AMI treated with ticagrelor or prasugrel who underwent percutaneous coronary intervention (PCI) were tested for circulating RP using flow cytometry with Thiazole orange staining at 3 time points at 2-4 days, 30-60 days and 1 year post PCI. Platelet reactivity was assessed using the VerifyNow P2Y12 assay at these time points (results in platelet reactivity units-PRU). Thirty-five patients were included in the study (mean age 62.6 ± 9.1 years, 82.9 % males). Median RP levels were similar at the first and second time points (17.5 %, IQR 25-75: 10.8-22.4 % and 14.9 %, IQR 25-75: 9.7-26.8 %, respectively; p = 0.75). However, RP levels after 1 year were significantly lower as compared to the first and second time points (10.5 % (IQR 25-75: 5.3-18.1 %), p = 0.005 and p = 0.01, respectively). Residual platelet reactivity was very low at all 3 time points (median PRU 25, IQR 25-75: 7-53) and did not change significantly between them (p = 0.66). No significant correlation was found between levels of RP and PRU at any given time point. RP levels of patients with AMI treated with prasugrel or ticagrelor decrease over time after the acute event. However, RP levels over time do not correlate well with residual platelet reactivity.

Effects of prasugrel pretreatment on angiographic myocardial perfusion parameters in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

“…We have recently suggested a possible mechanism for the reduced effect of prasugrel in STEMI patients, involving a higher rate of reticulated platelets in the acute phase, possibly reducing the effectiveness of therapy due to inherent hyperactivity of the platelets [13]. We have also shown a reduction in the proportions of reticulated platelets over time [14]. A recent article by Bernlochner et al [15] went further to compare the effect of reticulated platelets on prasugrel and ticagrelor, showing a greater impact on the former.…”

Reticulated Platelets: Changing Focus from Basics to Outcomes

“…86,87 In contrast to these findings, RP could not be correlated with platelet aggregation in another study of patients with ACS and treated with prasugrel. 50 However, the small number of patients, higher use of integrin α IIb β 3 antagonists and, most importantly, the very low platelet reactivity (median platelet reactivity unit value of 25) may have accounted for this finding. As prasugrel irreversibly binds to P2Y12 and has a half-life of about 7 hours, the RP newly introduced into circulation will be unexposed to the active metabolite at the end of its once daily administration.…”

“…49 Moreover, while RPs remain elevated for 30 to 60 days following myocardial infarction (MI), the level decreases after 1 year. 50 Thus, it is plausible that RPs may report long-term outcomes. Cesari et al measured RP levels at the time of presentation with ACS and found that RP levels independently predicted cardiovascular mortality at 1 year (OR ¼ 4.15, 95% CI: 1.24-13.91; p ¼ 0.02).…”

Platelet Turnover and Atherothrombosis

“…[46] были также получены поло-жительные корреляции между содержанием ретикулярных тромбоцитов и остаточной аг-регационной активностью тромбоцитов при применении прасугрела. Однако в более позд-ней работе (выполненной сходным составом ав-торов) таких корреляций выявлено не было [47]. Также подобных взаимосвязей не удалось об-наружить при анализе действия тикагрелора [47,48].…”

“…Однако в более позд-ней работе (выполненной сходным составом ав-торов) таких корреляций выявлено не было [47]. Также подобных взаимосвязей не удалось об-наружить при анализе действия тикагрелора [47,48]. Отрицательные результаты при полу-чении больными прасугрела и тикагрелора, по-видимому, обусловлены очень сильным по-давлением АДФ-индуцированной агрегации этими препаратами по сравнению с клопидог-релом и, соответственно, ее очень низким и слабовариабельным остаточным уровнем.…”