Platelet-derived microparticles during and after acute coronary syndrome

2012 ◽  
Vol 107 (06) ◽  
pp. 1122-1129 ◽  
Author(s):  
Mika Skeppholm ◽  
Fariborz Mobarrez ◽  
Karin Malmqvist ◽  
Håkan Wallén
Keyword(s):  
Clinical Trials ◽  
Acute Coronary Syndrome ◽  
Platelet Activation ◽  
Platelet Function ◽  
Plasma Concentrations ◽  
Healthy Controls ◽  
Antithrombotic Treatment ◽  
Coronary Syndrome ◽  
Flow Cytometric ◽  
Cell Fragments

SummaryAs microparticles are shedded upon platelet activation, and may be used to assess platelet function, we measured plasma concentrations of platelet-derived microparticles (PMPs) during and after an acute coronary syndrome (ACS). Fifty-one patients with ACS were investigated at admission, within 24 hours (before coronary angiography), and six months later. Sixty-one sex- and age-matched healthy controls were investigated once. PMPs were defined as particles <1.0 μm in size, negative to phalloidin (labels cell-fragments), and positive to CD61. Exposure of phosphatidylserine (PS+), CD62P and CD142 were also measured. Plasma concentrations of PS+PMPs exposing CD61, CD62P and CD142 were elevated 2.5, 6.0-, and 5.0-fold at admission (p<0.001 for all, compared to controls; aspirin only), decreased significantly 24 hours later following initiation of treatment with clopidogrel and subcutaneous anticoagulation (p<0.001 for all), and decreased even further six months later (p<0.01 for all). However, PS+PMPs exposing CD62P or CD142 were still between 1.2-and 2.3-fold higher than in controls (p<0.001 for both). The pattern for PS−PMPs during and after the ACS was very similar to that for PS+PMPs although the numbers were approximately 1/3 lower. In conclusion, PMP concentrations follow the pattern of platelet activation during and after an ACS. Decreased concentrations are observed after initiation of antithrombotic treatment, but PMP exposing CD62P or CD142 are still elevated after six months. Flow cytometric measurements of PMP in frozen-thawed samples enable studies of platelet function in larger clinical trials.

Abstract 17314: Impact of Mild Therapeutic Hypothermia on Platelet Inhibition in Acute Coronary Syndrome

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jan Kaufmann ◽  
Helena Stockmann ◽  
Philipp Stawowy ◽  
Kristof Graf ◽  
Eckart Fleck ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Antiplatelet Therapy ◽  
Therapeutic Hypothermia ◽  
Platelet Function ◽  
Mild Hypothermia ◽  
Plasma Concentrations ◽  
Mild Therapeutic Hypothermia ◽  
Light Transmittance ◽  
Coronary Syndrome ◽  
Platelet Aggregometry

Background: Mild therapeutic hypothermia (MTH) improves outcome for patients with acute coronary syndrome (ACS) after cardiac arrest (CA). Previous data point to an interaction between hypothermia and drug metabolism, thus potentially impacting on platelet function under antiplatelet therapy. Purpose: The aim of the study is to determine clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with mild hypothermia (33°C, n=12) compared with ACS patients (troponin positive) with normal body temperature (n=14). Methods: Platelet function was measured by light transmittance aggregometry (LTA), multiple electrode platelet aggregometry (MEA) and VASP phosphorylation analysis before, 2h, 4h and 24h after administration of a 600 mg clopidogrel loading dose. Furthermore, plasma concentrations of clopidogrel, the active thiol metabolite and the inactive carboxyl metabolite were determined. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. Mild hypothermia was carried out according to current guidelines for 24 hours at a target temperature of 33°C. Results: Plasma concentration of clopidogrel and metabolites were lower in the MTH group after 2h and 4h, respectively (all p<0.005). All platelet function tests showed an attenuated response to clopidogrel with respect to baseline platelet activity in the MTH group. This was significant for VASP analysis and LTA (p<0.05). Moreover, there was no difference in genotype and platelet function determined ex vivo with 33°C and 37°C, respectively. Conclusion: Inhibition of platelet function is decreased under MTH, presumably due to a diminished clopidogrel absorption and metabolization. Thus, these patients might have a higher risk for cardiovascular events despite antiplatelet therapy.

Glycoprotein Ia C807T: Polymorphisms and Their Association with Platelet Function in Patients with the Acute Coronary Syndrome

Cardiology ◽  
2015 ◽  
Vol 132 (4) ◽  
pp. 213-220 ◽  
Author(s):  
Qiang Zhang ◽  
Yiqi Jin ◽  
Dongmin Shi ◽  
Junrong Gong ◽  
Jing Liu ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Plasma Concentrations ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Antiplatelet Treatment ◽  
Coronary Syndrome ◽  
Granule Membrane ◽  
Dual Antiplatelet Treatment

Objectives: In the current study, we explored the relationship between glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the sensitivity to dual antiplatelet treatment after percutaneous coronary intervention. Materials and Methods: We conducted a case-control study in 220 patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls. The platelet GPIa C807T genotypes of patients and controls were determined, and platelet aggregation and plasma concentrations of α-granule membrane protein (GMP-140) were assessed following stimulation with arachidonic acid and adenosine diphosphate. Results: The frequency of the GPIa T allele was higher in the ACS group than in controls. In the ACS group, platelet aggregation was significantly higher in individuals with the T allele than in those with the C allele. Dual antiplatelet treatment reduced platelet aggregation in all three genotypes, and patients carrying the CC genotype were more sensitive to antiplatelet treatment than those with the T allele, particularly the ones with the TT genotype. There were no differences in plasma GMP-140 levels. Conclusions: The GPIa C807T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele may help to identify a group of patients who need more aggressive antithrombotic treatment.

scholarly journals Impact of timing of randomization after an acute coronary syndrome and subsequent events in patients with type 2 diabetes mellitus: an analysis of the EXAMINE trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Elharram ◽  
A Sharma ◽  
W White ◽  
G Bakris ◽  
P Rossignol ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Type 2 Diabetes Mellitus ◽  
Acute Coronary Syndrome ◽  
Primary Outcome ◽  
Funding Source ◽  
Coronary Syndrome ◽  
The Impact

Abstract Background The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes. Methods EXAMINE was a randomized trial of alogliptin versus placebo in 5380 patients with T2DM and a recent ACS. The primary outcome was a composite of CV death, non-fatal myocardial infarction [MI], or non-fatal stroke. The median follow-up was 18 months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8–34, 35–56, and 57–141 days. Results Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs. 33.0%), prior coronary artery bypass graft (9.6% vs. 15.9%), or atrial fibrillation (5.9% vs. 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio [aHR] 1.47; 95% CI 1.21–1.74) (Figure 1). Similarly, patients randomized early had an increased risk of recurrent MI (aHR 1.51; 95% CI 1.17–1.96) and HF hospitalization (1.49; 95% CI 1.05–2.10). Conclusion In a contemporary cohort of T2DM with a recent ACS, early randomization following the ACS increases the risk of CV events including recurrent MI and HF hospitalization. This should be taken into account when designing future clinical trials. Figure 1 Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Takeda Pharmaceutical

scholarly journals IL-17A Facilitates Platelet Function through the ERK2 Signaling Pathway in Patients with Acute Coronary Syndrome

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40641 ◽  
Author(s):  
Shuang Zhang ◽  
Jing Yuan ◽  
Miao Yu ◽  
Hong Fan ◽  
Zhang-Qiang Guo ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Signaling Pathway ◽  
Platelet Function ◽  
Coronary Syndrome

scholarly journals MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

2019 ◽  
Vol 119 (10) ◽  
pp. 1563-1572 ◽  
Author(s):  
Stefan Stojkovic ◽  
Anne Yaël Nossent ◽  
Paul Haller ◽  
Bernhard Jäger ◽  
Kris G. Vargas ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Treatment Response ◽  
Platelet Function ◽  
Ribonucleic Acids ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
Response Biomarkers

AbstractMicroribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

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