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.

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.

scholarly journals Acute Coronary Syndrome, Antiplatelet Therapy, and Bleeding: A Clinical Perspective

2020 ◽  
Vol 9 (7) ◽  
pp. 2064
Author(s):  
Gregorio Tersalvi ◽  
Luigi Biasco ◽  
Giacomo Maria Cioffi ◽  
Giovanni Pedrazzini
Keyword(s):  
Acute Coronary Syndrome ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Clinical Decision Making ◽  
Treatment Strategies ◽  
Clinical History ◽  
Bleeding Risk ◽  
Bleeding Complications ◽  
Coronary Syndrome

Inhibition of platelet function by means of dual antiplatelet therapy (DAPT) is the cornerstone of treatment of acute coronary syndrome (ACS). While preventing ischemic recurrences, inhibition of platelet function is clearly associated with an increased bleeding risk, a feared complication that may lead to significant morbidity and mortality. Since bleeding risk management is intrinsically associated with therapeutic adjustments undertaken during the whole clinical history of patients with acute coronary syndrome, single decisions taken from the very first day to years of follow-up might be decisive. This review aims at providing a clinically oriented, patient-tailored approach in reducing the risk and manage bleeding complications in ACS patients treated with DAPT. The steps in clinical decision making from the day of ACS to follow-up are analyzed. New treatment strategies to enhance the safety of DAPT are also described.

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.

Pharmacodynamic comparison of optimal platelet reactivity by multiple platelet function tests in Korean acute coronary syndrome patients with half-dose ticagrelor or prasugrel treatment

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.H Kim ◽  
C.D Jin ◽  
K Song ◽  
G.M Lee ◽  
H.Y Moon ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Standard Dose ◽  
Light Transmittance ◽  
Funding Source ◽  
Platelet Function Tests ◽  
Coronary Syndrome ◽  
Function Tests ◽  
Half Dose

Abstract Background East Asians treated with potent P2Y12 inhibitors, prasugrel or ticagrelor exhibit more potent platelet inhibition than clopidogrel. Whether half-dose de-escalation strategy would improve optimal platelet reactivity at maintenance in East Asian patients with acute coronary syndrome (ACS) remains uncertain. Method In de-escalation strategy single center study, eligible Korean ACS patients (n=96) were assigned to receive standard-dose ticagrelor (n=33), prasugrel (n=28), followed by half-dose reduction at 1 month for maintenance, and clopidogrel (n=35) as control. Platelet reactivity was measured by VerifyNow, light transmittance aggregometry (LTA) and multiple electrode aggregometry (MEA). The investigators aim to compare optimal platelet reactivity status (OPR, defined as 85–208 P2Y12 reaction unit [PRU] for VerifyNow (VN), 16%–47% for LTA and 19–46 U for MEA) among 3 different platelet function tests at 3 months post PCI. Results At 3 months, ticagrelor achieved significantly lower PRU (17 [6–51] vs. 95 [61–151] vs. 172 [111–204]) than prasugrel and clopidogrel, resulting OPR rate 10% vs. 57.7% vs. 60.0%, respectively. Similar results were observed at LTA method (2% [0–12] in ticagrelor vs. 18% [13–22] in prasugrel vs. 18% [11–30] in clopidogrel), with OPR rate 11.8% vs. 69.2% vs. 50.0%, respectively. However, platelet reactivity was similar by MEA method (16 [13–20] in ticagrelor vs. 17 [13–22] in prasugrel vs. 19 [14–28] in clopidogrel), with OPR rate 33.3% vs. 40.0% vs. 42.0%, respectively (all p&gt;0.005). Among the three tests, resulting higher correlation between VN and LTA (r=0.745), MEA and LTA vs. MEA and VN showed lower correlations (r=0.412 and r=0.303). (Fig.) Conclusion In Korean ACS patients with half-dose de-escalation strategy after 1 month, OPR rate in ticagrelor is still rare during 3-month treatment by VN and LTA methods, however, prasugrel appears comparable to clopidogrel. VN/LTA might overestimate platelet function than MEA or MEA underestimate OPR rate than VN/LTA. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea

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