scholarly journals Hypoxia Modulates Platelet Purinergic Signalling Pathways

2019 ◽  
Vol 120 (02) ◽  
pp. 253-261 ◽  
Author(s):  
Gordon G. Paterson ◽  
Jason M. Young ◽  
Joseph A. Willson ◽  
Christopher J. Graham ◽  
Rebecca C. Dru ◽  
...  
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Platelet Reactivity ◽  
Clinical Importance ◽  
Adenosine Diphosphate ◽  
Purinergic Signalling ◽  
Systematic Assessment ◽  
Vasp Phosphorylation ◽  
The Impact ◽  
Induced Aggregation

Abstract Background Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. Methods Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. Results Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. Conclusion Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation.

scholarly journals Thromboelastometry and Platelet Function during Acclimatization to High Altitude

2018 ◽  
Vol 118 (01) ◽  
pp. 063-071 ◽  
Author(s):  
Alistair Rocke ◽  
Gordon Paterson ◽  
Matthew Barber ◽  
Alexander Jackson ◽  
Shona Main ◽  
...  
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coagulation Factors ◽  
Significant Rise ◽  
Fibrinogen Concentration ◽  
Increased Risk ◽  
Using Data

AbstractInteraction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of patients following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5,200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen concentration that occurred during acclimatization. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100 closure times and increased platelet aggregation in response to adenosine diphosphate. Post-expedition results were consistent with the normalization of coagulation following descent to sea level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a prothrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events.

The Influence of Altitude on Erythropoietin Resistance Index in Maintenance Hemodialysis Patients: Data from Tibetan Plateau

2020 ◽  
pp. 1-6
Author(s):  
Yan Wang ◽  
Zong-hui Dang ◽  
Liang-ying Gan ◽  
Ciren Luobu ◽  
Lei Zhang ◽  
...  
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Resistance Index ◽  
Hemoglobin Concentration ◽  
Maintenance Hemodialysis ◽  
Autonomous Region ◽  
Tibet Autonomous Region ◽  
Dialysis Vintage ◽  
Peking University ◽  
The Impact

Background: It is known that hypoxia influences many of the biologic processes involved in erythropoiesis; therefore, the high-altitude hypoxia may affect erythropoietin (EPO) responsiveness in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the impact of altitude on EPO responsiveness in MHD patients. Methods: In this retrospective study, MHD patients from Tibet Autonomous Region People’s Hospital (3,650 m above sea level) and Peking University People’s Hospital (43.5 m above sea level) were recruited between May 2016 and December 2018. Patients were divided into 2 groups according to altitude. Variables including age, sex, dialysis vintage, dialysis modality, duration of EPO use, EPO doses, and laboratory tests were collected and analyzed. EPO responsiveness was measured in terms of the EPO resistance index (ERI). ERI was defined as the weekly weight-adjusted dose of EPO (IU/kg/week) divided by hemoglobin concentration (g/dL). The association between ERI and altitude was estimated using a multivariable linear regression model. Results: Sixty-two patients from Tibet Autonomous Region People’s Hospital (high-altitude [HA] group) and 102 patients from Peking University People’s Hospital (low-altitude [LA] group) were recruited. The ERI for HA group and LA group was 6.9 ± 5.1 IU w−1 kg−1 (g/dL)−1 and 11.5 ± 6.4 IU w−1 kg−1 (g/dL)−1, respectively. After adjusting for covariates by multivariable regression, altitude was independently associated with ERI (R2 = 0.245, p < 0.001). Conclusion: Altitude had an independent negative correlation with ERI. This result supported the hypothesis that altitude-associated hypoxia improved EPO responsiveness in MHD patients.

scholarly journals The Impact of Cold Storage on Adenosine Diphosphate-Mediated Platelet Responsiveness

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e163-e172
Author(s):  
Juergen Koessler ◽  
Philipp Klingler ◽  
Marius Niklaus ◽  
Katja Weber ◽  
Angela Koessler ◽  
...  
Keyword(s):  
Cold Storage ◽  
Whole Blood ◽  
Room Temperature ◽  
Purinergic Receptor ◽  
Adenosine Diphosphate ◽  
Receptor Expression ◽  
Activation Markers ◽  
Inhibitory Pathways ◽  
The Impact ◽  
Induced Aggregation

Abstract Introduction Cold storage of platelets is considered to contribute to lower risk of bacterial growth and to more efficient hemostatic capacity. For the optimization of storage strategies, it is required to further elucidate the influence of refrigeration on platelet integrity. This study focused on adenosine diphosphate (ADP)-related platelet responsiveness. Materials and Methods Platelets were prepared from apheresis-derived platelet concentrates or from peripheral whole blood, stored either at room temperature or at 4°C. ADP-induced aggregation was tested with light transmission. Activation markers, purinergic receptor expression, and P2Y12 receptor function were determined by flow cytometry. P2Y1 and P2X1 function was assessed by fluorescence assays, cyclic nucleotide concentrations by immunoassays, and vasodilator-stimulated phosphoprotein (VASP)-phosphorylation levels by Western blot analysis. Results In contrast to room temperature, ADP-induced aggregation was maintained under cold storage for 6 days, associated with elevated activation markers like fibrinogen binding or CD62P expression. Purinergic receptor expression was not essentially different, whereas P2Y1 function deteriorated rapidly at cold storage, but not P2Y12 activity. Inhibitory pathways of cold-stored platelets were characterized by reduced responses to nitric oxide and prostaglandin E1. Refrigeration of citrated whole blood also led to the attenuation of induced inhibition of platelet aggregation, detectable within 24 hours. Conclusion ADP responsiveness is preserved under cold storage for 6 days due to stable P2Y12 activity and concomitant disintegration of inhibitory pathways enabling a higher reactivity of stored platelets. The ideal storage time at cold temperature for the highest hemostatic effect of platelets should be evaluated in further studies.

Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover

2016 ◽  
Vol 116 (11) ◽  
pp. 941-948 ◽  
Author(s):  
Thomas Nührenberg ◽  
Michael Amann ◽  
Marco Cederqvist ◽  
Pascal Kleiner ◽  
Christian M. Valina ◽  
...  
Keyword(s):  
Platelet Count ◽  
Drug Exposure ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Underlying Mechanism ◽  
Entire Cohort ◽  
Reticulated Platelets ◽  
Impedance Aggregometry ◽  
The Impact

SummaryReticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all timepoints (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.Supplementary Material to this article is available online at www.thrombosis-online.com.

Impact of aspirin dose on adenosine diphosphate-mediated platelet activities

2013 ◽  
Vol 110 (10) ◽  
pp. 777-784 ◽  
Author(s):  
Antonio Tello-Montoliu ◽  
Estela Thano ◽  
Fabiana Rollini ◽  
Ronakkumar Patel ◽  
Ryan E. Wilson ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Stable Coronary Artery Disease ◽  
Adenosine Diphosphate ◽  
P2y12 Receptor ◽  
Reactivity Index ◽  
Receptor Blockade ◽  
Aspirin Dose ◽  
Dosing Regimens ◽  
The Impact

SummaryDifferent aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y12 receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y12 naïve were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 ± 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 μM) of prasugrel’s active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y12 inhibition measured by VASP-PRI (p<0.001). However, there were no differences according to aspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 ïM: p=0.888; 3 ïM: p=0.524; 10 ïM: p=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced platelet aggregation (p<0.001 for all measures), irrespective of aspirin dose. In conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12 receptor blockade modulates platelet reactivity mediated by alternative activators.

Reduced coagulation at high altitude identified by thromboelastography

2012 ◽  
Vol 107 (06) ◽  
pp. 1066-1071 ◽  
Author(s):  
Daniel Martin ◽  
Jim Pate ◽  
Andre Vercueil ◽  
Patrick Doyle ◽  
Michael Mythen ◽  
...  
Keyword(s):  
Oxygen Saturation ◽  
High Altitude ◽  
Sea Level ◽  
Whole Blood ◽  
Maximum Amplitude ◽  
Peripheral Oxygen Saturation ◽  
Blood Samples ◽  
Whole Blood Samples ◽  
Α Angle ◽  
The Impact

SummaryThe impact of hypoxaemia on blood coagulation remains unclear despite use of a variety of measures to address the issue. We report the first use of thromboelastography (TEG) at high altitude to describe the dynamics of clot formation in whole blood samples. Seventeen healthy volunteers ascended to 5,300 m following an identical ascent profile; TEG measurements at 4,250 m and 5,300 m were compared with those from sea level. Peripheral oxygen saturation (SpO2) and haematocrit were also measured. Ascent resulted in a decline in SpO2 from 97.8 (± 1.2) % at sea level to 86.9 (± 3.3) % at 4,250 m and 79.5 (± 5.8) % at 5,300 m (p<0.001); haematocrit rose from 43.7 (± 2.8) % at sea level, to 46.7 (± 3.9) % and 52.6 (± 3.2) % at 4,250 m and 5,300 m, respectively (p<0.01). TEG reaction (R)-time and kinetic (K)-time were both increased at 5,300 m compared to sea level, 8.95 (± 1.37) minutes (min) to 11.69 (± 2.91) min (p=0.016) and 2.40 (± 0.66) min to 4.99 (± 1.67) min (p<0.001), respectively. Additionally the alpha (α)- angle was decreased from 57.7 (± 8.2) to 51.6 (± 6.4) (p<0.001). There was no change in maximum amplitude (MA) on ascent to altitude. These changes are consistent with an overall pattern of slowed coagulation at high altitude.

scholarly journals Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers

2019 ◽  
Vol 119 (05) ◽  
pp. 735-743 ◽  
Author(s):  
Sukhi Singh ◽  
Tor Damén ◽  
Andreas Nygren ◽  
Caroline Shams Hakimi ◽  
Sofia Ramström ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Clinical Importance ◽  
Receptor Activation ◽  
Clot Formation ◽  
Bleeding Complications ◽  
Impedance Aggregometry ◽  
Perioperative Bleeding ◽  
Adrenaline Infusion ◽  
Induced Aggregation

Background Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo. Methods Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 µg/kg/min. The aggregation increased from median 17 (25−75th percentiles: 14−31) to 25 (21−34) aggregation units (p = 0.012) at 0.10 µg/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22–35] to 46 [38−57%]) and P-selectin expression (from 3.7 [3.0−4.3] to 7.7 [4.7−8.6%]), both p = 0.012. Adrenaline infusion reduced clot formation time (97 [89−110] to 83 [76−90] seconds, p = 0.008) and increased maximum clot firmness (59 [57−60] to 62 [61−64] mm, p = 0.007). Conclusion Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations. Trial Registry Number ClinicalTrials.gov NCT03441412.

scholarly journals Prasugrel in critically ill patients

2017 ◽  
Vol 117 (08) ◽  
pp. 1582-1587 ◽  
Author(s):  
Christian Schoergenhofer ◽  
Eva-Luise Hobl ◽  
Thomas Staudinger ◽  
Walter Speidl ◽  
Gottfried Heinz ◽  
...  
Keyword(s):  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Platelet Reactivity ◽  
Prospective Trial ◽  
Adenosine Diphosphate ◽  
High Shear Rates ◽  
Coefficients Of Variation ◽  
Medical University ◽  
Induced Aggregation

SummaryWhile prasugrel is indicated for the treatment of myocardial infarction, its effects in the most severely affected patients requiring intensive care is unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics of prasugrel in critically ill patients. Twenty-three patients admitted to medical intensive care units, who were treated with 10 mg prasugrel once daily, were included in this prospective trial. Critically ill patients responded poorly to daily prasugrel treatment: adenosine diphosphate (ADP)-induced aggregation in whole blood classified 65 % (95 % confidence intervals (CI) 43–84 %) of patients as having high on treatment platelet reactivity, platelet function under high shear rates even 74 % (95 %CI 52–90 %). There was only limited additional inhibition provided 2 hours after the next dose of prasugrel. In contrast, insufficient inhibition of the target was only seen in 26 % (95 %CI 10–48 %) of patients as measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. Low effective plasma levels of prasugrel active metabolite were measured at trough [0.5 (quartiles 0.5–1.1) ng/ml at baseline], and 2 hours after intake [5.7 (3.8–9.8) ng/ml], but showed coefficients of variation of ~70 %. In sum, inhibition of platelet aggregation by prasugrel is not uniform but highly variable in critically ill patients, similar to clopidogrel in a general population. The pharmacokinetic measurements indicate that poor absorption/metabolism of prasugrel may partly contribute while inflammation induced heightened intrinsic platelet reactivity may also play a role.Supplementary Material to this article is available online at www.thrombosis-online.com.Note: This work was performed at the Medical University of Vienna, Austria.

scholarly journals Antiaggregatory activity of new 1-ethylxanthine cyclohexylammonium salt in vitro

2013 ◽  
Vol 94 (5) ◽  
pp. 692-695
Author(s):  
F Kh Kamilov ◽  
G A Timirkhanova ◽  
A I Samorodova ◽  
A V Samorodov ◽  
F A Khaliullin ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Platelet Aggregation ◽  
Aggregate Size ◽  
Adenosine Diphosphate ◽  
Biochemical Effect ◽  
Platelet Aggregate ◽  
Antiaggregatory Activity ◽  
The Impact ◽  
Induced Aggregation

Aim. To study the biochemical effect on hemostasis of a new cyclohexilammonium salt of 2-[1-ethyl-3-methyl-7(dioxotiethanyl-3)xantinyl-8-thio]acetic acid in vitro. Methods. Thromboelastography was performed using the citrate blood samples of healthy male donors. Global hemostatic effect, fibrinogen and platelet function, fibrinolysis and clot strength, and stability were analyzed at thromboelastography. The impact of firstly synthesized xantine derivative and pentoxifylline on the functional activity of platelets in vitro was studied using a laser analyzer of platelet aggregation. Adenosine diphosphate, collagen, epinephrine and ristocetin induced clotting were registered. General clotting characteristics, maximal aggregation values, maximal aggregation speed, mean platelet aggregate size, activity of platelet-derived factor 3, level of platelet-derived factor 4 were measured. Release of platelet-derived factors 3 and 4 at platelet aggregation were assessed after adenosinediphosphate-induced aggregation and centrifugation. Results. Cyclohexylammonium salt of 2-[1-ethyl-3-methyl-7-(dioxotiethanyl-3)xantinyl-8-thio]acetic acid in vitro showed antiaggregatory activity that exceeds such of pentoxifylline. It has been revealed that the second platelet aggregation wave, that is induced by small dose of adenosinediphosphate, is absent in the presence of the new cyclohexylammonium salt, lag-period in collagen-induced platelet aggregation elongates, and availability and release of platelet-derived factors 3 and 4 decreases. Conclusion. The research findings show potentially high antiaggregatory activity of 2-[1-ethyl-3-methyl-7-(dioxotiethanyl-3)xantinyl-8-thio]acetic acid cyclohexylammonium salt as an inhibitor of platelet release reaction.

scholarly journals Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients

2019 ◽  
Vol 6 (4) ◽  
pp. 203-210 ◽  
Author(s):  
Joshua P Lewis ◽  
Joshua D Backman ◽  
Jean-Luc Reny ◽  
Thomas O Bergmeijer ◽  
Braxton D Mitchell ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Cardiovascular Death ◽  
Individual Variability ◽  
Clinical Event ◽  
Major Adverse Cardiovascular Events ◽  
Risk Alleles ◽  
The Impact ◽  
Response Score

Abstract Aims  Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. Methods and results  We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10−54; CES1 G143E, P = 1.3 × 10−16; CYP2C19*17, P = 9.5 × 10−10; CYP2B6 1294 + 53 C &gt; T, P = 3.0 × 10−4; CYP2B6 516 G &gt; T, P = 1.0 × 10−3; CYP2C9*2, P = 1.2 × 10−3; and CYP2C9*3, P = 1.5 × 10−3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14–2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35–14.27, P = 0.01) compared to patients who carried six or fewer of these alleles. Conclusion  Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.

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