Sensitive objective markers for measuring aspirin responsiveness in pregnancy: An explorative scoping review.

BACKGROUND: Aspirin is frequently used in pregnancy to decrease the risk of developing pre-eclampsia. Studies have highlighted this potential benefit which in theory happens by inhibition of platelet function. However, questions remain on the appropriate dosing and the reliability of serum markers in determining aspirin responsiveness in pregnancy (ARP). OBJECTIVE: review the literature on ARP and identify the gaps, followed by investigating the objective biomarkers used to assess ARP. This includes the factors associated such as aspirin formulations, doses, and patient comorbidities. METHODS: A comprehensive search was conducted using keywords such as 'aspirin', 'pregnancy', and 'responsiveness' in relevant databases such as PubMed, SCOPUS, Cochrane from inception to March 2024. Our inclusion criteria enrolled pregnant women aged 18 years old and above, irrespective of their trimester status, who were prescribed aspirin for any medical indication. RESULTS: The research findings encompass three key areas. Firstly, examination of the impact of different aspirin formulations on responsiveness revealed no significant differences between different formulations. Secondly, nine papers were identified with varied dosages of administered aspirin, highlighting a need for standardized approach to dosing, and investigating higher dosing and its impact. Thirdly, there is a lack of consensus on biomarkers used to assess ARP. Finally, this synthesis sheds light on prognostic factors of developing aspirin non-responsiveness, such as medical comorbidities. CONCLUSION: This scoping review identifies several residual uncertainties on ARP. The main gaps are validation of serum markers, understanding the influence of underlying morbidity on ARP, and determining appropriate aspirin dosing in pregnancy.

Early detection of resistance to dual antiplatelet therapy in patients who have undergone percutaneous coronary intervention using the VerifyNow test and associated factors.

Resistance to dual antiplatelet therapy (DAPT), including aspirin and clopidogrel, in patients who have undergone percutaneous coronary intervention (PCI) leads to the inability to prevent thrombotic complications. The present study aimed to evaluate early resistance to aspirin and clopidogrel in patients following PCI using the VerifyNow test and associated factors. A total of 50 patients diagnosed with acute coronary syndromes (ACS) who underwent emergency PCI and received DAPT were recruited in the present study. The detection of resistance to aspirin and clopidogrel was performed using the VerifyNow system. Resistance to aspirin was determined with VerifyNow Aspirin >550 aspirin reaction units (ARU). Resistance to clopidogrel was determined with VerifyNow P2Y12 >208 P2Y12 reaction units (PRU). The resistance rate to aspirin was 14%, while the resistance rate to clopidogrel was higher, at 34%. There were 2 patients with resistance to aspirin and clopidogrel (4%). Univariable logistic regression analysis revealed that diabetes, the use of ß-blockers, and low levels of hemoglobin and hematocrit were associated with resistance to clopidogrel. Following multivariable logistic regression analysis, only the use of ß-blockers was truly associated with resistance to clopidogrel. On the whole, the results of the present study may also prove to be helpful in the selection of therapeutic drugs for patients undergoing PCI and who are diagnosed with ACS.

Direct Oral Anticoagulant Treatment for Atherosclerosis-Induced Aortic Mural Thrombus in an Elderly Male With Aspirin Resistance.

Aortic mural thrombus is associated with atherosclerosis in a vast majority of cases and could result in multiple organ damage, leading to higher morbidity and mortality rates. Although aspirin could be effective for primary prevention in atherosclerosis-induced aortic mural thrombus, aspirin resistance, which refers to the inadequate response to aspirin therapy, allows the progression of thrombus. Classically, warfarin could be an effective treatment for thromboembolic diseases, while in recent years, direct oral anticoagulants (DOACs) have shown superior safety and efficacy, particularly in elderly patients. This report presents the case of an elderly male with chronic aortic mural thrombi due to atherosclerosis and aspirin resistance who achieved favorable outcomes following treatment with DOACs. DOACs could be a possible option for managing aortic mural thrombus with aspirin resistance.

Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study.

INTRODUCTION: This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81 mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81 mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). METHODS: Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14 days, with a washout period of 28 days, followed by Vazalore® LD PL-ASA daily for 14 days, again followed by ARU testing. RESULTS: Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. CONCLUSIONS: There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024.

Aspirin resistance in pregnancy is associated with reduced interleukin-2 (IL-2) concentrations in maternal serum: Implications for aspirin prophylaxis for preeclampsia.

OBJECTIVES: To evaluate the impact of aspirin resistance on the incidence of preeclampsia and maternal serum biomarker levels in pregnant individuals at high-risk of preeclampsia receiving low dose aspirin (LDA). STUDY DESIGN: We performed a secondary analysis of a randomized, placebo-controlled trial of LDA (60 mg daily) for preeclampsia prevention in high-risk individuals (N = 524) on pregnancy outcomes and concentrations of PLGF, IL-2, IL-6, thromboxane B2 (TXB2), sTNF-R1 and sTNF-R2 from maternal serum. MAIN OUTCOME MEASURES: LDA-resistant individuals were defined as those having a TXB2 concentration >10 ng/ml or <75 % reduction in concentration at 24-28 weeks after LDA administration. Comparisons of outcomes were performed using a Fisher's Exact Test. Mean concentrations of maternal serum biomarkers were compared using a Student's t-test. Pearson correlation was calculated for all pairwise biomarkers. Longitudinal analysis across gestation was performed using linear mixed-effects models accounting for repeated measures and including BMI and maternal age as covariates. RESULTS: We classified 60/271 (22.1 %) individuals as LDA-resistant, 179/271 (66.1 %) as LDA-sensitive, and 32/271 (11.8 %) as non-adherent. The prevalence of preeclampsia was not significantly different between the LDA and placebo groups (OR = 1.43 (0.99-2.28), p-value = 0.12) nor between LDA-sensitive and LDA-resistant individuals (OR = 1.27 (0.61-2.8), p-value = 0.60). Mean maternal serum IL-2 concentrations were significantly lower in LDA-resistant individuals relative to LDA-sensitive individuals (FDR < 0.05). CONCLUSIONS: These results suggest a potential role for IL-2 in the development of preeclampsia modulated by an individuals' response to aspirin, presenting an opportunity to optimize aspirin prophylaxis on an individual level to reduce the incidence of preeclampsia.

Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.

BACKGROUND: Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks. METHODS: We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors. RESULTS: The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p < 0.01) and PRU (r = 0.503, R2 = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks. CONCLUSIONS: This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03823274.

Defining light transmission aggregometry cutoff values for clopidogrel and aspirin resistance in flow diversion treatment of intracranial aneurysms.

OBJECTIVE: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications. METHODS: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values. RESULTS: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51. CONCLUSIONS: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Prevalence of risk factors for venous thromboembolism and aspirin resistance in Australian patients undergoing total hip and knee arthroplasty.

INTRODUCTION: Aspirin is used for venous thromboembolism (VTE) prophylaxis after total hip and knee arthroplasty (THA/TKA). However, its efficacy is unclear in patients with multiple VTE risk factors and at risk of aspirin resistance (AR). BACKGROUND AND AIMS: To determine the prevalence of risk factors for VTE and AR in patients after THA/TKA and to determine the relationship between risk factors and drugs prescribed for thromboprophylaxis. METHODS: A retrospective cohort study of elective-THA/TKA in six Australian hospitals over a 1-year period. Medical records were manually reviewed to determine demographics, thromboprophylaxis regimen and presence of risk factors. The relationship between individual and cumulative risk factors with the thromboprophylaxis regimen was determined. RESULTS: In total, 1011 patients were included with a mean (SD) age of 65.9 (±11.0) years, and 56.4% were female. The five most prevalent risk factors were obesity (59.1%), age ≥65 years (58.2%), hypertension (45.3%), dyslipidaemia (35.9%) and diabetes (19.7%). Most patients had ≥1 risk factor for VTE (93.6%) and AR (93.6%), with 49.0% and 35.0% having ≥3 concurrent VTE and AR risk factors, respectively. The only significant relationship between risk factors and drugs was diabetes (P < 0.01). Rivaroxaban was more commonly used as the number of concurrent VTE risk factors increased (P < 0.05). CONCLUSION: Patients had a high prevalence of VTE and AR risk factors, suggesting aspirin may not be beneficial in many patients. Only diabetes was linked to the selection of thromboprophylaxis. Patients who received rivaroxaban had a greater average number of VTE risk factors. Guidelines should promote individualised prescribing in higher-risk patients.

Epoxidase inhibitor-aspirin resistance and the relationship with genetic polymorphisms: a review.

Strokes are the leading cause of death in most regions of the world. Epoxidase inhibitors include the drug aspirin (acetylsalicylic acid). Aspirin is widely used as first-line treatment for the prevention of cardiovascular and cerebrovascular diseases in at-risk patients. However, patients using conventional doses of aspirin can still develop ischaemic cardiovascular and cerebrovascular diseases, a phenomenon known as aspirin resistance. The occurrence of aspirin resistance hinders the prevention and treatment of ischaemic cardiovascular and cerebrovascular diseases. There are many factors affecting aspirin resistance, such as sex, drug dose, metabolic disease, genetic polymorphisms, drug interactions and pharmacokinetics. Genetic polymorphism refers to the simultaneous and frequent presence of two or more discontinuous variants or genotypes or alleles in a population of organisms. Platelets contain a large number of highly polymorphic transmembrane glycoprotein receptors encoded by two or more isomeric alleles. Changes in gene polymorphisms in various pathways during platelet aggregation can lead to aspirin resistance. This narrative review describes the gene polymorphisms that have been demonstrated to be significantly associated with aspirin resistance. Research on the mechanisms of aspirin resistance and increased knowledge should provide accurate drug guidance in individuals that require first-line antiplatelet therapy.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

Zhilong Huoxue Tongyu capsule ameliorates platelet aggregation and thrombus induced by aspirin in rats by regulating lipid metabolism and microRNA pathway.

INTRODUCTION: Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported. OBJECTIVES: This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. METHODS: An AR model was established through treatment with a high-fat, high-sugar, and high-salt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA-126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction. RESULTS: Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p. CONCLUSION: This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.

The Effect of the ABCB1(MDR-1) C3435T Polymorphism in Turkish Patients with Aspirin Resistance in Acute Ischemic Stroke.

Recurrence of thrombotic events during aspirin therapy is known as aspirin resistance (AR). This study aimed to investigate the rate of AR, the factors influencing AR in patients with acute ischemic stroke under regular aspirin use, and the relationship between AR and ABCB1 (MDR-1) C3435T (rs1045642) polymorphism. Throughout this multicenter prospective study, 174 patients with acute ischemic stroke who had been prescribed aspirin for at least one month due to the risk of vascular disease, along with 106 healthy volunteers, were included as part of the study group. The results of our study indicate that AR was detected in 21.3% of the patient group. According to the results of an analysis of the polymorphism of the ABCB1 C3435T in patients with AR compared to those with aspirin sensitivity, patients with AR possessed more heterozygous (CT) and homozygous genotypes (TT) than those with aspirin sensitivity (p = 0.001). Based on multivariate logistic regression analysis of factors affecting AR in acute ischemic stroke patients, hypertension (OR: 5.679; 95% CI: 1.144-28.19; p = 0.034), heterozygous (CT) genotype (OR: 2.557; 95% CI: 1.126-5.807; p = 0.025), increased platelet values (OR: 1.005; 95% CI: 1.001-1.009; p = 0.029), and CRP/albumin values (OR: 1.547; 95% CI: 1.005-2.382; p = 0.047) were found to be associated with a greater risk of AR. The presence of heterozygous (CT) genotype in the ABCB1 C3435T gene region in the Turkish population is associated with an increased risk of AR. When planning aspirin therapy, it is crucial to consider the ABCB1 (MDR-1) C3435T polymorphism.

The Diabetic Platelets.

This communication describes the platelet morphology and physiology noted in persons with diabetes and its complications. It reviews the effects of glucose lowering drugs on platelet function, and summarizes the role of anti-platelet drugs in diabetes management.

Key Mutant Genes and Biological Pathways Involved in Aspirin Resistance in the Residents of the Chinese Plateau Area.

INTRODUCTION: Aspirin is used to prevent and treat cardiovascular diseases; however, some patients develop aspirin resistance. AIM: We aimed to explore the potential molecular mechanisms underlying aspirin resistance in people living in the Chinese plateau area. METHODS: In total, 91 participants receiving aspirin treatment from the Qinghai plateau area were divided into the aspirin resistance and aspirin sensitivity groups. Genotyping was performed using the Sequence MASSarray. Differentially mutated genes between the two groups were analyzed using MAfTools. The annotation of differentially mutated genes was conducted based on the Metascape database. RESULTS AND DISCUSSION: In total, 48 differential SNP and 22 differential InDel mutant genes between the aspirin resistance and aspirin sensitivity groups were screened using Fisher's exact test (P < 0.05). After the χ2 test, a total of SNP mutant genes, including ZFPL1 and TLR3, and 19 InDel mutant genes were found to be differentially expressed between the two groups (P < 0.05). Functional analysis revealed that these differential SNP mutations were mainly enriched in aspirin resistance pathways, such as the Wnt signaling pathway. Furthermore, these genes were related to many diseases, including various aspirin indications. CONCLUSION: This study identified several genes and pathways that could be involved in arachidonic acid metabolic processes and aspirin resistance progression, which will provide a theoretical understanding of the molecular mechanism of aspirin resistance.

Application and monitoring of antiplatelet drugs in children with Kawasaki disease / 国际儿科学杂志

Long-term antiplatelet therapy is critical for children with Kawasaki disease.Commonly used antiplatelet drugs have their own advantages and adverse reactions, so they need to be chosen carefully.Some studies have shown that drug resistance may occur in children with Kawasaki disease during antiplatelet therapy, which increases the risk of cardiovascular adverse events, and platelet aggregation function needs to be monitored during medication.This paper reviews the antiplatelet drugs in common use, the drug resistance of antiplatelet drugs and the detection methods of platelet aggregation function in Kawasaki disease, which is helpful to improve the safety of drugs use and reduce the incidence of complications in children.

DNA methylation profile in the whole blood of acute coronary syndrome patients with aspirin resistance.

BACKGROUND: Aspirin resistance (AR) results in major adverse cardiovascular events, and DNA methylation might participate in the regulation of this pathological process. METHODS: In present study, a sum of 35 patients with AR and 35 non-AR (NAR) controls were enrolled. Samples from 5 AR and 5 NAR were evaluated in an 850 BeadChip DNA methylation assay, and another 30 AR versus 30 NAR were evaluated to validate the differentially methylated CpG loci (DML). Then, qRT-PCR was used to investigate the target mRNA expression of genes at CpG loci. Finally, Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to reveal the enriched pathways. RESULTS: The AR and NAR groups displayed significant differences in DNA methylation at 7707 positions, with 270 hypermethylated sites (e.g., cg09555818 located in APOC2) and 7437 sites hypomethylated sites (e.g., cg26828689 located in SLC12A5). Six DML were validated by pyrosequencing, and it was confirmed that DNA methylation (cg16391727, cg21008208, cg21293749, and cg13945576) was related to the increasing risk of AR. The relative mRNA expression of the ROR1 gene was also associated with AR (p = 0.007), suggesting that the change of cg21293749 in DNA methylation might lead to differential ROR1 mRNA expression, ultimately resulting in AR. Furthermore, the identified differentially methylated sites were associated with the molecular pathways such as circadian rhythms and insulin secretion. CONCLUSION: Hence, the distinct DNA methylation might play a vital role in the biological regulation of AR through the pathways such as circadian rhythms.

Does proton pump inhibitor reduce the antiaggregant efficacy of aspirin in ischemic stroke?

OBJECTIVE: To evaluate the effect of using acetylsalicylic acid (aspirin) together with lansoprazole in the secondary prevention of ischemic stroke. MATERIALS AND METHODS: 199 patients with a diagnosis of ischemic stroke and transient ischemic attack (TIA) using 100 mg aspirin regularly were included in the study. All patients were evaluated for the presence of aspirin resistance before starting the study. 57 patients with aspirin resistance were excluded from the study. The remaining 142 patients were divided into two groups: the 1st group consisted of those with stomach discomfort and the 2nd group consisted of those without stomach discomfort. Patients in group 1 were given 30 mg of lansoprazole taken before breakfast in addition to aspirin therapy. All patients were re-evaluated for the presence of aspirin resistance at a one-month follow-up. The antiaggregant activity was evaluated by the impedance aggregometry method in both groups. RESULTS: Of 142 patients, 75 were in group 1, and 67 were in group 2. There was no difference between the two groups in terms of age and gender distribution of vascular risk factors. There was no statistically significant difference between the two groups in terms of aspirin efficacy. The dose of aspirin was increased in patients with aspirin resistance (AR). CONCLUSION: The combination of 30 mg lansoprazole and 100 mg aspirin does not cause a decrease in antiaggregant activity in the early period, but chronic use was not evaluated in this study. Patients with AR may benefit from an increase in the dose of aspirin.

Factors Associated with Aspirin Resistance in Hong Kong Chinese Patients with Stable Coronary Heart Disease Using the Multiplate® Analyzer and Serum Thromboxane B2.

Introduction: Aspirin resistance may be associated with various conditions. We measured serum thromboxane B2 (TXB2) and platelet function using the Multiplate® Analyzer with arachidonic acid (ASPI) in patients on long term aspirin therapy to identify aspirin resistance and associated factors. Materials and Methods: Chinese patients with stable coronary heart disease had samples for serum TXB2 and ASPI measurement taken before and 1 h after taking a morning dose of 80 mg aspirin. Results: In 266 patients with mean age 66.6 ± 10.7 years, 17% were female and 55% were current or previous smokers. TXB2 and ASPI measurements were significantly higher before the dose than at 1 h post dose, with 46% of subjects having high ASPI values (AUC > 300 AU*min) pre dose compared with 27% at 1 h post dose. TXB2 and ASPI measures of platelet aggregation showed weak correlations, which were only significant before the dose (r = 0.219, p = 0.001). Increased ASPI measurements were associated with white blood cell (WBC) count, haematocrit, platelet count and heart rate at 24 h post dose but only with WBC count, smoking history and heart rate at 1 h post dose. Diabetes was not associated with reduced platelet response to aspirin. The WBC count associated with aspirin resistance was over 6.55 × 109/L by receiver operating characteristic analysis. Conclusions: The antiplatelet response to aspirin was reduced in a large proportion of patients. Patients with higher WBC count within the normal range appear to be at increased risk of aspirin resistance. Higher or more frequent doses of aspirin may be needed in many patients.

Personalized allocation of acetylsalicylic acid therapy for secondary prevention of coronary artery disease.

Background: A single-daily dose of 75 mg of acetylsalicylic acid inhibits 100% of thromboxane-B2 synthesis within 30-60 min. Thromboxane-B2 synthesis then recovers slowly as new platelets are released from the bone marrow. Normally, only 10% of the platelets are replaced daily by new platelets entering circulation. Hence, 24 h after a dose of acetylsalicylic acid, thromboxane-B2 synthesis is still suppressed by more than 90%. Hence, there is an adequate anti-platelet effect even after 24 h of acetylsalicylic acid intake. However, some patients treated with once-daily acetylsalicylic acid may have an incomplete 24-h suppression of thromboxane-B2 synthesis due to increased platelet turnover. The response could be improved in such patients by twice-daily acetylsalicylic acid administration. This study aimed to identify such a group of patients who would benefit from a twice-daily dose of acetylsalicylic acid. Materials and methods: Serum thromboxane-B2 levels were measured in 79 patients with coronary artery disease receiving 75 mg of acetylsalicylic acid for secondary prophylaxis. Serum levels of thromboxane-B2 were measured after 4 and 24 h of acetylsalicylic acid intake. Patients were then classified into three groups: steady suppression group (serum thromboxane B2 is adequately suppressed at 4 and 24 h), i.e., adequate response to acetylsalicylic acid; fast recovery group (more than 10% rise in serum thromboxane-B2 levels at 24-h when compared to at 4-h) and non-responders (serum thromboxane-B2 levels of >3,100 pg/ml after 4 h of acetylsalicylic acid intake). Patients in the fast recovery group were given twice-daily acetylsalicylic acid and thromboxane-B2 levels were re-measured. Results: A total of 20 patients (24.3%) had steady suppression of thromboxane-B2 and 11 patients (13.9%) belonged to the fast recovery group, i.e., thromboxane-B2 levels were adequately suppressed at 4 h but had recovered by more than 10% at 24 h; which was adequately suppressed by twice-daily acetylsalicylic acid (p 0.004). A total of 48 patients (60.8%) were non-responders. Conclusion: Twice-daily acetylsalicylic acid may be beneficial if serum thromboxane-B2 levels at 4 h are <3,100 and >3,100 pg/ml at 24 h. If thromboxane-B2 levels at 4 and 24 h is <3100 pg/ml but if there is a >10% rise in serum thromboxane B2 at 24 h as compared to that at 4 h, then twice-daily acetylsalicylic acid should be considered. However, if thromboxane-B2 at 4 and 24 h is >3,100 pg/ml consider switching over to a P2Y12 inhibitor.

Genetic Association Study and Machine Learning to Investigate Differences in Platelet Reactivity in Patients with Acute Ischemic Stroke Treated with Aspirin.

Aspirin resistance (AR) is a pressing problem in current ischemic stroke care. Although the role of genetic variations is widely considered, the data still remain controversial. Our aim was to investigate the contribution of genetic features to laboratory AR measured through platelet aggregation with arachidonic acid (AA) and adenosine diphosphate (ADP) in ischemic stroke patients. A total of 461 patients were enrolled. Platelet aggregation was measured via light transmission aggregometry. Eighteen single-nucleotide polymorphisms (SNPs) in ITGB3, GPIBA, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1 and PEAR1 genes and the intergenic 9p21.3 region were determined using low-density biochips. We found an association of rs1330344 in the PTGS1 gene with AR and AA-induced platelet aggregation. Rs4311994 in ADRA2A gene also affected AA-induced aggregation, and rs4523 in the TBXA2R gene and rs12041331 in the PEAR1 gene influenced ADP-induced aggregation. Furthermore, the effect of rs1062535 in the ITGA2 gene on NIHSS dynamics during 10 days of treatment was found. The best machine learning (ML) model for AR based on clinical and genetic factors was characterized by AUC = 0.665 and F1-score = 0.628. In conclusion, the association study showed that PTGS1, ADRA2A, TBXA2R and PEAR1 polymorphisms may affect laboratory AR. However, the ML model demonstrated the predominant influence of clinical features.