Acetylsalicylic Acid Resistance Research Articles

Aspirin resistance in patients with ventricular assist devices-A follow-up study.

Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well-known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial. We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function. We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86-20.64], p = 0.003; IPA: OR = 12.14, CI [3.00-49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders. Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients.

Assessment of Aspirin and Clopidogrel Resistance in Patients Undergoing Cardiovascular Surgery: A Single Center Cross-Sectional Study.

We aimed to investigate the antiplatelet drug resistance utilizing light transmission-lumiaggregometry (LT-LA) and platelet function analyzer-100 (PFA-100) in patients undergoing cardiovascular surgery. The study included 60 patients diagnosed with stable coronary artery disease and peripheral vascular diseases that required surgery. The participants were divided into three groups: patients receiving Aspirin (ASA) (n=21), patients receiving Clopidogrel (CLO) (n=19), and patients receiving dual therapy (ASA+CLO) (n=20). Aggregation and secretion tests in LT-LA and closure time in PFA-100 were used to measure antiplatelet drug resistance. Based on the ADP-induced aggregation test, 43% of patients were resistant to ASA, 22% to CLO, and 15% to dual therapy. Diabetes, hypertension, and hyperlipidemia were the most commonly identified comorbid disorders. In patients with comorbid risk factors, the median value of platelet aggregation response to ADP was significantly higher in the ASA group than in the CLO and dual therapy groups (p=0.0001). In patients receiving ASA monotherapy, the maximum amplitude of aggregation response to platelet agonists was equal to or more than 70% in 43% of patients for ADP and 28% for collagen in LT-LA. Elevated ADP (≥0.29 nmol) and collagen (≥0.41 nmol)-induced ATP release were found in 66% of patients utilizing ADP agonist and 80% of patients using collagen agonist undergoing ASA therapy in LT-LA. Closure times in PFA-100 were normal in 28% of patients using collagen-ADP cartridges and 62% of patients using collagen-epinephrine (CEPI) cartridges who received ASA. Recurrent thrombosis and bleeding were observed in 12 (20%) of patients with cardiovascular disease. Three of these individuals (25%) showed ASA resistance, which showed normal response to ADP-induced aggregation (≥70%) and secretion (≥0.29 nmol), as well as normal CEPI closure times. Our findings suggest that antiplatelet drug monitoring with LT-LA and PFA-100 may be useful in high-risk and complicated cardiovascular patients.

11-dehydrothromboxane B2 as a marker of acetylsalicylic acid resistance in patients with stable coronary artery disease

Introduction. Acetylsalicylic acid (ASA, aspirin) resistance is the inability to reduce thromboxane A2 synthesis in platelets and inhibit platelets activation and aggregation while taking ASA. Assessment of urinary 11-dehydrothromboxane B2 (11-dhTxB2) levels is one of the methods to identify aspirin resistance. Our research aimed to investigate whether urinary 11-dhTxB2 levels and other clinical and laboratory parameters are associated with a history of major adverse cardiovascular events (MACE) including myocardial infarction and ischaemic stroke in aspirin-treated patients with stable coronary artery disease. Patients and methods. In a cross-­sectional study we investigated 82 patients with stable coronary artery disease who took ASA at doses of 75–150 mg/day. We used the evaluation of the urinary 11-dhTxB2 levels standardized by creatinine as a method to identify aspirin resistance. Statistical analysis was performed using Mann-­Whitney U-test, ROC-analysis and multivariable logistic regression. Results. The medians of urinary 11-dehydrothromboxane B2 level in patients with and without MACE were 587.8 (Q1-Q3 512.8–800.3) pg/mg creatinine and 438.3 (Q1–Q3 337.6–577.9) pg/mg creatinine, respectively (p=0.001). The threshold level of urinary 11-dhTxB2, which predicted a high risk of aspirin resistance, was 521.1 pg/mg creatinine, and in 36 (43.9 %) patients the concentration of the 11-dhTxB2 exceeded this level. The regression model characterising the dependence of the presence of a history of MACE was constructed. It included platelet count, urinary levels of 11-dhTxB2 and the presence of type 2 diabetes. Sensitivity and specificity of the model were 55 % and 88.9 %, respectively. Conclusions. The results of the study demonstrate that the antiplatelet effect of aspirin is weaker in stable coronary artery disease patients with a history of MACE than in those without a history of MACE.

CARC13: Evaluation of Response to Aspirin Platelet Therapy and Hemocompatibility-Related Adverse Events with the HeartMate 3 Left Ventricular Assist Device

Background: Left ventricular assist device (LVAD) patients usually are prescribed a combination of anticoagulation and aspirin (ASA) therapy. HeartMate 3 (HM3) demonstrates reduced hemocompatibility-related adverse events (HRAEs) including stroke, thrombosis and bleeding. However, it’s not known whether ASA responders vs. non-responders are non-inferior in the incidence of HRAEs, and whether there are temporal changes in ASA sensitivity during HM3 support. Methods: This prospective, observational, single-center cohort study included 21 HM3 LVAD patients (Age: 59.0±11.1 years, female: 4.8%, BMI: 29.6±6.1kg/m2) implanted between 2019 and 2021, with serial ASA platelet sensitivity assays (VerifyNow Assay). ASA platelet therapy resistance was defined by ASA reactivity units (ARU) > 550. Primary endpoint was the incidence of HRAEs (ASA responders vs. non-responders) 6 months before initial assessment and until the next outpatient follow-up visit (3 months ± 30 days). Secondary endpoint was the temporal change in ASA resistance. Results: Eight (38.1%) patients were ASA resistant at the first ARU assessment (426 days after HM3 implantation) and 21.1% (p=0.38) during follow-up, without ARU changes over time (512±64 vs. 491±53, p=0.22). ASA responders and non-responders received a comparable ASA daily dose per-protocol (108±28mg vs. 100±28mg, p=0.43), without significant differences in baseline demographics (age: 62±9 vs. 55±14 years, p=0.17; female: 0% vs. 12.5%, p=0.38; BMI: 29±7 vs. 32±3, p=0.55; ischemic heart failure: 46.2% vs. 25.0%, p=0.45) or risk factors (Atrial fibrillation: 30.8% vs. 25.0%, diabetes: 30.8% vs. 37.5% and stroke history: 15.4% vs. 12.5%, p>0.99). The incidence of HRAEs was comparable between ASA responders and non-responders 6 months before the first measurement (15.4% vs. 0.0%, p=0.26) and between the two ARU measurements (0.0% vs. 12.5%, p=0.22). Conclusion: Although the ASA resistance varies considerably between LVAD outpatients, without significant changes over time, the HM3 demonstrated excellent hemocompatibility. Further large-scale multicenter studies are needed to confirm the findings of this study that ASA plays only a minor role in antithrombotic treatment with HM3 and can be safely removed.

Recurrent Coronary Artery Disease Due to Acetylsalicylic Acid Resistance May Be Related to COX-1 and COX-2 Mutations

Recurrent Coronary Artery Disease Due to Acetylsalicylic Acid Resistance May Be Related to COX-1 and COX-2 Mutations

High on-treatment platelet reactivity to aspirin in patients after myocardial infarction

Aspirin (ASA) is widely used as an antiplatelet therapeutic drug in secondary prevention. Last years brought many reports on ASA resistance or high on-treatment platelet reactivity (HTPR) to aspirin.This study is a post-hoc prospective analysis with 30 patients evaluated during follow up on average of 6.3 years after hospitalization from myocardial infarction. The examined population was divided into two subgroups according to the response to ASA. In order to estimate the function of blood platelets and their responsiveness to acetylsalicylic acid therapy, ASPI-test was used. The measurements were performed by the method of whole blood impedance aggregometry. During long-term follow up significantly higher percentage of high platelet reactivity was observed, compared with previous visits (p = 0.00001). Considering clinical endpoints of the research that were connected with coronary disease, no differences were obtained.The frequency of HTPR to aspirin in this study was higher than data reported in literature among subjects with CV diseases. In long-term observation the highest percentage of ASA non-responders was reported (58.6%). HTPR to aspirin did not affect the presence of the clinical endpoints for the study.

COX-1, COX-2 and CYP2C19 variations may be related to cardiovascular events due to acetylsalicylic acid resistance.

In some stent implanted patients, cardiovascular events (CE) may occur. Acetylsalicylic acid (ASA) is routinely administered to these patients in order to prevent the occurrence of CE. CE may be related to gene variations which cause ASA resistance (AR). Therefore, it was aimed to investigate the relationship between COX-1, COX-2, CYP2C9 and CYP2C19 variations with CE due to AR. Seventy-four stent implanted patients, using 100mg of ASA per day during five years were enrolled into the study. Following stent implantation, thirty-eight patients who had a CE within five years due to AR and 36 patients without CE were enrolled in patient and control group, respectively. AR was confirmed by platelet aggregation testing. After DNA isolation from blood; COX-1, COX-2, CYP2C19 and CYP2C9 variations were investigated with real-time polymerase chain reaction. At the end of this study, heterozygous genotype of COX-1 was found statistically high in patients whereas heterozygous genotype of CYP2C19*17 was found statistically high in controls. The presence of C and G allele in COX-1 and COX-2 were found statistically high in patients, respectively. The presence of T allele in CYP2C19*17 was found statistically high in controls. Heterozygous genotype of COX-1 variation was found statistically high in patients who have AR. Additionally heterozygous genotype of CYP2C19*17 was found statistically high in patients who have low thrombosis risk. COX-1 and COX-2 gene mutations may increase the risk of CE due to AR whereas CYP2C19*17 may have a protective effect in this process.

Assessment of acetylsalicylic acid and clopidogrel resistance results of the patients with significant stenosis on carotid color Doppler ultrasonography

Assessment of acetylsalicylic acid and clopidogrel resistance results of the patients with significant stenosis on carotid color Doppler ultrasonography

Monitoring of Aspirin Therapy in Patients with Cerebrovascular Pathology

Aim. Evaluation of various methods for determining the effectiveness of aspirin therapy and aspirin resistance in patients with cerebrovascular disease (CVD) depending on the presence of type 2 diabetes mellitus (T2DM).Materials and methods. The prospective study included 78 patients with various manifestations of CVD. All patients received acetylsalicylic acid (ASA) 75 mg daily. Along with a comprehensive clinical examination, a laboratory assessment of platelet function with the usage of Born method with aggregometer, a detailed biochemical blood test (including the determination of the small subunit of low density lipoprotein [s-LDL]), as well as therapeutic drug monitoring of salicylates were performed on a gas chromatograph-mass spectrometer.Results. In 53% of cases, the absence or insufficiency of the effect of ASA on platelet aggregation was noted. Two subgroups were separately identified: with T2DM; (n=40) and without T2DM (n=38). Insufficient effect of the drug on platelet aggregation characteristics were observed in 65% of patients with T2DM and in 38% without T2DM. The differences were revealed between the groups in triglycerides, s-LDL, glycemic and glycated hemoglobin (p &lt;0.05). In the group of patients with T2DM, the median ASA concentration was 0.01 [0; 0.32] μg/ml, and salicylic acid (SA)– 0.20 [0; 0.39] μg/ml, while in patients without T2DM higher values were noted: ASA 0.29 [0.15; 0.55] μg/ml, SA – 0.33 [0.05; 0.73] μg/ml. A decrease in the concentration of ASA was associated with an increase in the level of ADP-induced platelet aggregation. There was an increase in the levels of ADPand adrenaline-induced platelet aggregation with a decrease in the concentration of ASA (p=0.004) and SA (p=0.006). Therapeutic drug monitoring revealed a more significant decrease in ASA level in T2DM than in the comparison group (p=0.025).Conclusion. It is advisable to monitor aspirin therapy both with the assessment of platelet aggregation and with therapeutic drug monitoring. The relationship between the level of ASA and SA in the blood plasma and the functional activity of platelets was confirmed. The presence of T2DM is associated with a decrease in the concentration of ASA and aspirin resistance detected in therapeutic drug monitoring.

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome

ObjectivesMany studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting. Materials and methodsWe performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors. ResultsWe included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 – 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 – 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 – 203.14). ConclusionWe found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting.

Assessment of platelet function and resistance to aspirin and clopidogrel in patients with peripheral arterial disease undergoing percutaneous transluminal angioplasty

Introduction: Analysis of platelet function, acetylsalicylic acid (ASA) and clopidogrel resistance in patients with peripheral arterial disease (PAD) undergoing percutaneous transluminal angioplasty (PTA), the impact of procedure on this phenomenon, connection with diabetes, hypertension, smoking. Material and methods: The study included 72 patients, with a group of patients taking ASA on a permanent basis and a group of patients in whom treatment was implemented after the procedure. Patients were also divided according to the antiplatelet therapy applied, either double-therapy, or ASA monotherapy. Daily doses were 75 mg. Three methods were used for the evaluation of the platelet function: IVY bleeding time, cytometric evaluation of platelet surface antigen (CD62p and CD63) expression and hemostasis measurement by PFA-200®. Results: In the PFA-200 analysis, ASA resistance was found in 37.8% (64.7% were tobacco smokers) before surgery. Patients not taking ASA before, after PTA and first dose of ASA presented resistance in 63%. The first dose of clopidogrel after surgery was associated with resistance in 73.7%. Significant differences in the expression of CD62p and CD63 markers before and after PTA were observed. According to IVY method, aspirin resistance was found in 40% of patients permanently receiving ASA. Conclusions: Patients with PAD who undergo PTA are resistant to ASA in 40%, smoking is associated with this phenomenon. PTA increases the expression of CD62P and CD63, and thus the platelet activation, which is not adequately prevented by antiplatelet drugs at a dose of 75 mg. Dual antiplatelet therapy reduces the activation of thrombocytes more than the monotherapy of ASA.

Overview of Aspirin and Platelet Biology

Aspirin (ASA) has historically been one of the most important drugs in cardiology and has long been the cornerstone of antiplatelet therapy. Although its role in acute coronary syndrome remains undisputed, emerging data suggest that reappraisal of the efficacy of long-term ASA in some primary and secondary prevention may be warranted. The aim of this review is to place these new results in the context of previous evidence on aspirin by appraising the current body of evidence on its use of for cardiovascular diseases. This overview first summarizes the history of the discovery of aspirin, as well as its pharmacology and the concept of ASA resistance. We subsequently recapitulate the evidence of ASA on primary prevention and secondary prevention starting from the classical studies in order to serve as an introductory background to the examination of the most recent clinical trials that will be performed in the rest of the articles of this Supplement. Although the benefit of ASA in acute coronary syndrome remains incontrovertible, emerging evidence challenge the universal need for primary prevention, or for lifelong treatment in secondary prevention or all adults with stable coronary disease who are at highest risk for ASA-induced bleeding. The role of aspirin is quickly changing in recent times and this review provides a review for the clinician about the current role of this drug in cardiovascular care.

Antiplatelet Direncinin Miyokard İnfarktüsü Sonrası Sol Ventrikül Trombüsü Gelişimine Etkisi: Prospektif, Gözlemsel, Vaka-kontrol Çalışması

Objective: Left ventricular (LV) thrombus is a serious complication of acute myocardial infarction (MI). In this study, the effect of biochemical resistance to antiplatelet agents used after ST elevation MI on LV thrombus development was investigated. Material and Methods: Patients who were diagnosed with anterior MI and undergone primary percutaneous coronary intervention were included in this study. The patients were divided into two groups: Patients with thrombus (Group 1) and the patients without thrombus (Group 2). PFA-100 platelet analyzer was used to measure platelet reactivity. Clopidogrel resistance was defined as collagen adenosine 5-diphosphate closure time (COLL/ADP CT) <120 seconds and acetylsalicylic acid (ASA) resistance was defined as collagen epinephrine closure time (COLL/EPI CT) <180 seconds. Group 1 and Group 2 were compared with ASA and clopidogrel resistance. Results: The mean CT for COLL/EPI was similar in two groups (Group 1: 221.4±64.8 sec, Group 2: 217.7±70.2 sec; p=0.81). ASA resistance was detected in 24 (26.7%) patients in the whole patient group. There was no difference between the two groups in terms of ASA resistance [8 patients (26.7%) in Group 1, 16 patients (26.7%) in Group 2; p=1.0]. The mean closure times for COLL/ADP were similar in two groups (Group 1: 145.9±63.9 sec, Group 2: 155.9±63.9 sec; p=0.48). Clopidogrel resistance was detected in 27 (30%) patients in the whole patient group. There was no difference between two groups in terms of clopidogrel resistance [9 (30%) patients in Group 1, 18 (30%) patients in Group 2; p=1.0]. There was no difference between two groups in patients with both clopidogrel and aspirin resistance. Conclusion: In vivo resistance to dual antiplatelet therapy does not appear to be an effective mechanism in the development of LV thrombus after MI.

Prevalence and Features of Aspirin Resistance in Patients with Coronary Artery Disease

Purpose. To determine the frequency of development of aspirin resistance in patients with coronary heart disease and to identify risk factors for the development of resistance to acetylsalicylic acid (ASA) in patients with coronary heart disease. Material and Methods: 96 patients were enrolled in this study with stable forms of ischemic heart disease who received a standard dose of aspirin 75 mg/day for a long time. Patients were divided into 4 groups according to the prescription of ASA. Group 1 consisted of patients who did not receive aspirin, the second group consisted of patients taking aspirin up to 1 year, the third group consisted of patients taking aspirin from 1 year to 5 years, and the fourth group included patients taking aspirin for more than 5 years. An addition, according to the results of determining aspirin resistance, the patients were divided into 2 groups. Platelet aggregation was measured using a laser analyzer: adenosine diphosphate (ADP) with 1.0 and 5.0 μmol was used. Resistance criterion: ADP ≥72% at 5.0 μmol. Results: 17.7% of patients who took aspirin in a standard dose of 75 mg/day were resistant to aspirin, and a third of them took aspirin for more than 5 years. According to the results of a study of platelet aggregation activity, the average degree of platelet aggregation with 5.0 μmol of ADP was 82.4% in patients with no reaction to aspirin. An inadequate response to aspirin was reliably often observed in women and the elderly (58.8% and 70.5%). When analyzing the results of routine laboratory studies in patients with aspirin resistance, there was a tendency to higher levels of cholesterol and glucose (p˂0.05). Possible risk factors for the development of ASA resistance are hypercholesterolemia and hyperglycemia, since aspirin resistance was more common in patients with diabetes (13 out of 17) and obesity (11 out of 17).Conclusion: High rates of ADP-induced platelet aggregation were obtained in ¼ patients with coronary heart disease. A

Aspirin Sensitivity Wanes Early during Left Ventricular Assist Device Support

Aspirin (ASA) therapy is recommended in left ventricular assist device (LVAD) patients to prevent thromboembolic complications. Up to 30% of LVAD patients may demonstrate ASA resistance, which has been related to thrombotic complications. However, it is unknown whether individual patients exhibit temporal alterations in ASA sensitivity during LVAD support. This project evaluated changes in ASA platelet inhibition over the first 6 months of LVAD support. We hypothesized that ASA platelet inhibition would wane after the initial post-implant period. Patients who underwent placement of Heartware or Heartmate III LVAD at our institution and had serial ASA platelet sensitivity assays were included for analysis. ASA responsiveness was determined by VerifyNow assay with results expressed in aspirin reactivity units (ARU). ASA platelet resistance was defined by ARU greater than 550. ASA responsiveness was assessed post-implant after 5 days, 3 months, and 6 months. Out of 28 patients included for analysis only 7% were ASA-resistant at baseline. However, 32% of patients were ASA-resistant at 3 months and 28% at 6 months. (Figure 1). ASA-resistance was significantly more prevalent at 3-months (OR 6.1, p=0.03) with a trend toward increased prevalence at 6 months (OR 4.1, p=0.1) compared to early post-implant. ASA dose was increased in 4% and 14.3% of ASA-resistant patients at 3 and 6 months, respectively. ASA responsiveness not only varies between patients, but can significantly change within individual LVAD patients over time. Over the first 3 months, the odds of ASA-resistance increased 6-fold and remained relatively constant at 6 months despite aspirin dose adjustment. Serial assessment of ASA responsiveness may help better identify LVAD patients at risk for thrombotic or bleeding complications. Further study is required into the both the clinical implications and the mechanism of waning aspirin sensitivity in LVAD patients.

Acetylsalicylic acid resistance in patients with acute ischemic stroke

This paper investigates the sensitivity to aspirin in patients with ischemic stroke in the early recovery period by optical aggregometry. The obtained results revealed individuals insensitive to aspirin. The aim is to detect the incidence of biochemical aspirin resistance among patients with history of ischemic stroke on the background of aspirin. Material and methods. Clinical and laboratory analysis of 80 patients with acute ischemic stroke who received 75 mg of acetylsalicylic acid (ASA) before bedtime as a preventive measure. Sensitivity to aspirin was determined by optical aggregatometry with adrenaline inducer. With an increase in optical permeability above 60%, aspirin resistance was ascertained. Results. It was found that among the surveyed patients, 20 (25%) were aspirin resistant, that is, the use of ASA for the purpose of secondary prevention in them will not prevent the recurrence of a vascular catastrophe. Conclusions. Monitoring the state of platelet link using optical aggregatometry allows timely to detect the lack of response to ASA and necessitates correction of the applied antiplatelet therapy.

Проблемы резистентности к ацетилсалициловой кислоте в профилактике ишемического инсульта (обзор литературы)

Проблемы резистентности к ацетилсалициловой кислоте в профилактике ишемического инсульта (обзор литературы)

Association of T715P (RS6136), M62I (RS2228315), S290N (RS6131), V640L (RS6133) polymorphisms in the P-selectin gene and its ligand with acetylsalicylic acid resistance in patients with coronary artery disease after coronary artery bypass grafting

Aim.To study the association of T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) polymorphisms in the P-selectin gene with resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease after coronary artery bypass grafting (CABG).Material and methods. The study included 90 patients aged 61,5±6,9 years (70 men and 20 women) with II-IV functional class (FC) angina pectoris, according to the Canadian Cardiovascular Society grading. The atherosclerotic nature of coronary artery disease is confirmed by coronary angiography. Patients stopped taking antiplatelet agents before CABG for at least 5 days. The aggregation study was carried out with an optical aggregometer using ADP inducers (5 pM) and arachidonic acid (1 µМ) before CABG, on 1-3 and 8-10 days after surgical treatment.DNA samples were examined for the presence of T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) polymorphisms in the P-selectin gene using realtime PCR with allele-specific primers.Results.When comparing aPTT, fibrinogen level, platelet aggregation activity with ADP inducers (5 µМ) and arachidonic acid (1 µМ), no differences were found among groups of patients with homozygous and heterozygous variants of the studied polymorphisms genotypes, both before and on 1-3, 8 -10 days after CABG. Regarding presence of ASA resistance, patient groups with homozygous variants of genotypes (T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133)) did not statistically differ in prevailing or rare alleles from the corresponding groups with heterozygous genotypes. In the first 10 days of the postoperative period, thrombotic events (4,4%) were observed in 4 patients in the study group: acute myocardial infarction, acute cerebrovascular accident. Regarding frequency of adverse events in the first 10 days after CABG, between groups of patients with homozygous variants of the studied genotypes (T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) in prevailing allele and groups with heterozygous variants of the corresponding genotypes there were also no statistically significant differences.Conclusion.Rs6133, rs6163, rs2228315, rs6131 polymorphisms in the platelet P-selectin gene are not associated with ASA resistance and are not associated with increased platelet aggregation activity in patients with coronary artery disease. The rare T, C, G, A alleles of the studied polymorphisms do not lead to an increase in the risks of adverse events in the first 10 days after CABG.

Aspirin Resistance: Cardiovascular Risk Game Changer.

Aspirin (ASA) is the most used medication on the globe. ASA is a primary pillar of the secondary prevention of cardiovascular atherothromboembolic events. However, a fraction of the population does not respond to ASA as expected in a unique phenomenon called ASA resistance. Multiple mechanisms were described and studied in the literature to explain this phenomenon. ASA resistance is an interesting phenomenon that is worth studying and reviewing. Mechanisms behind this resistance are various and although the rarity of some, it is crucial for the modern health provider to be aware of such phenomenon and its possible explanations to provide more efficient preventive cardiology practice. Our study aimed to review and conclude the evidence behind ASA resistance and its implication on the cardiovascular health. We searched databases like PubMed, EMBASE, Ovid by midline, and Google Scholar for published articles and abstracts. Our systemic search revealed more than 100 articles in relation to ASA resistance. We selected 40 articles, which were relevant for this review. Various mechanisms were described in the literature, with few of them very well documented and understood. Main mechanisms include medication nonadherence, interaction with proton pump inhibitors, esterase-mediated ASA inactivation, post-coronary artery bypass grafting (CABG) MRP-4-mediated ASA consumption, cyclooxygenase-1 (COX-1) polymorphisms, high platelet turnover-associated regeneration of platelet COX-1, and the documented platelet ability of de novo COX-1 synthesis in response to thrombin and fibrinogen. Multiple mechanisms of ASA resistance were described in the literature. Awareness of such interaction is important for medical practitioners. Bottom line, further studies and reviews are needed to further study this phenomenon and its implication on the cardiovascular health and hence reaching a valid evidence-based conclusion that might change the practice and improve the patient preventive health care.

Assessment of the relationship between platelet reactivity, vascular risk factors and gender in cerebral ischaemia patients.

Excessive activation and platelet aggregation play important roles in the aetiopathogenesis of cerebral ischaemia. The aim of this study was to assess the relationship between platelet reactivity, gender and vascular risk factors in cerebral ischaemia patients. The research is useful because we found high risk groups of inefficient aspirin treatment in cerebral ischaemia patients. The study involved 101 patients, including 69 patients with ischaemic stroke and 32 patients with transient ischaemic attack. The assessment of platelet reactivity was made within 24 hours of the disease onset using two aggregometric methods: impedance and optical. Resistance to acetylsalicylic acid among people with cerebral ischaemia was estimated at 30.69% using impedance aggregometry and 9.2% using optical aggregometry. There were no differences in platelet reactivity or ASA resistance between the groups of patients with stroke and TIA in either method. In the whole group of patients (p = 0.04), and in the group of patients with stroke (p = 0.0143), higher reactivity of platelets was observed by impedance aggregometry in men than in women. In the whole group of patients (p = 0.0229), and in the subgroup with stroke (p = 0.0123), it was shown that aspirin resistance is significantly more common in the subgroup of men than in women. In patients suffering from nicotine addiction, significantly higher platelet reactivity was found in the whole group of patients (p = 0.004), as well as in the subgroup of patients with stroke (p = 0.0135). There are no differences between platelet reactivity and the incidence of aspirin resistance in patients with stroke and TIA. Male gender and smoking are associated with greater reactivity of platelets and more frequent occurrence of acetylsalicylic acid resistance in patients with cerebral ischaemia. Dual antiplatelet therapy or clopidogrel treatment should be considered in smoking males with cerebral ischaemia due to the high risk of aspirin inefficiency.