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@#Objective To determine the prevalence of aspirin (ASA) resistance in pediatric patients with congenital heart disease and evaluate whether postoperative thrombosis is associated with aspirin resistance. Methods A total of 52 patients undergoing high-risk congenital cardiac surgery were recruited in a prospective cohort study at Fuwai Hospital from August 2016 to December 2017. There were 29 males and 23 females with a median age of 8 months (6 d to 13 years). The response to aspirin was determined using the thromboelastography with platelet mapping (TEG-PM) system several days after administration. According to the arachidonic acid (AA) inhibition< 50% or not, they were divided into an ASA resistance group (n=14) and an ASA sensitivity group (n=38). Risk factors of ASA resistance were identified using univariate and multivariate analysis. Patients were monitored prospectively for three months for the development of a thrombosis event. Results Of 52 children analyzed, 14 (26.9%) were ASA resistance. The prevalence of thrombosis after ASA antiplatelet therapy was 5.9%. Dose escalation based on aspirin testing was performed in 3 of 14 patients, and the ASA sensitivity was observed in 1 patient. No correlation was found between ASA resistance and postoperative thrombosis (r=0.04, P=0.80). Conclusion Postoperative thrombosis is not associated with aspirin resistance in these patients. Our findings also suggest that resistance may be due to lack of aspirin doses, monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients.
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Objective To study the impact of aspirin resistance(AR)on the recurrence of artery athero-sclerotic cerebral infarction,and analyze the risk factors of AR. Methods According to TOSAT classification, newly diagnosed cerebral infarction patients with artery atherosclerotic cerebral infarction were selected into groups,and aspirin enteric-coated tables(ASP)was used to prevent platelet aggregation.One week later,the inhi-bition rate of platelet was detected by thrombelastogram(TEG),and the patients were divided into aspirin sensi-tive(AS)group and AR group,and were followed-up for at least 6 months.According to whether they were recur-rent cerebral infarction,the patients were divided into recurrent group and non-recurrent group. Then,statistical analysis was conducted.Results The incidence rate of AR in recurrent group was significantly higher than that in non-recurrence group(P < 0.05);the recurrence rate of cerebral infarction in AR group was significantly higher than that in AS group(P<0.05).When compare the clinical indexes between the recurrence group and non-recur-rence group,age,diabetes,TC,Hcy,Apo-a in the two groups were different(P<0.05).In recurrent group,the distribution of diabetes,LDL-C and Hs-CRP were different between AR and AS group(P<0.05).Age,gender, hypertension,diabetes,Hs-CRP and TC were risk factors for AR.Conclusions AR plays an important role in the relapse of artery atherosclerotic cerebral infarction and it is more likely to occur especially accompanied by adverse factors such as underlying diseases. TEG can be used to detect AR rapidly and conveniently,which has practical significance in preventing recurrent cerebral infarction.
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Objeetive To investigate the relationships of CYP2C19 genotype polymorphism with platelet inhibition rate and clopidogrel low responsiveness in patients taking percutaneous coronary intervention (PCI) during perioperative administration of clopidogrel.Methods 404 patients taking clopidogrel after PCI were included from February 2016 to February 2017.They were divided into three groups:fast metaboliszer,moderate metaboliszer and slow metabolizer,according to the CYP2C19 genotype.Platelet inhibition rate induced by adenosine diphosphate (ADP) was detected by thrombelastogram,platelet inhibition rate ＜ 30％ was defined as clopidogrel low responsiveness (CLR) group and the relationships between the three groups were analyzed in view of CYP2C19 genotype and the platelet inhibition rate and the clopidogrel low responsiveness.Results (1) The proportions of the three groups was 45.5％,45.3％ and 9.2％ in the 404 patients,no statistically significant difference among the three groups in general data (age,sex,platelet,hypertension,diabetes mellitus,hyperlipidemia) (P ＞ 0.05).(2) There was no statistically significant difference in the platelet inhibition rate between the three groups (P =0.312).(3) There was no significant difference in the clopidogrel low responsiveness between the three groups (P =0.295),with the fast metabolizer group vs.intermediate metabolizer (P =0.522),the fast metabolizer group vs.the slow metabolizer (P =0.117) and the intermediate metabolizer group vs.slow metabolizer (P =0.255).Conclusion There is no correlation of CYP2C19 genotype with platelet inhibition rate and clopidogrel low responsiveness in patients taking clopidogrel after PCI.Only the detection of CYP2C19 genotype may not accurately predict the antiplatelet aggregative activity of clopidogrel.
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Objective To discuss the relationships of the genotype of cytochrome P450 2C19 (CYP2C19) gene and and clopidogrel responsiveness.Methods The study enrolled 110 patients with acute myocardial infarction who were treated with clopidogrel in Tiantan Hospital of Beijing from November 2012 to May 2014.Patients were treated by aspirin and clopidogrel.CYP2C19 polymorphisms were detected by genotype testing kits.Platelet inhibition rates were measured by thrombelastography to represent the antiplatelet effect of clopidogrel.The platelet inhibition rates of clopidogrel were compared among different genotypes.Results Compared with carriers of CYP2C19 * 2 or * 3 reduced-function allele,CYP2C19 * 1 wild type had higher platelet inhibition rate of clopidogrel ((35.73 ± 19.29)％ vs.(48.30± 20.84)％),and the difference was significant(t =3.264,P＜0.05).There was no difference between intermediate metabolizer((35.72± 19.27)％) and poor metabolizer((35.75±19.89)％;P＞0.05).The frequency of wild-type homozygotes CYP2C19 * 1/* 1 was higher in responders than in low responders(frequency of low reaction group CYP2C19 * 1/* 1 14 cases (40.0％),* 1/.2 10 cases(28.6％),* 1/* 3 4 cases(11.4％),* 2/* 2 5 cases(14.3％),* 2/* 3 2 cases (5.7％),frequency of reaction group were 45 cases (60.0％),15 cases (20.0％),4 cases (5.3 ％),7 cases (9.3％),4 cases(5.3％);x2 =3.838,P =0.05).Conclusion Polymorphism of gene CYP2C19 is associated with different responses to clopidogrel.CYP2C19 * 2/ * 3 reduced-function allele is associated with low response to clopidogrel.
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Objective: To investigate the effect of clopidogrel on antiplatelet therapy in patients with coronary artery disease (CAD) combining chronic kidney disease (CKD) in order to provide a medication reference in clinical practice. Methods: We retrospectively investigated 423 CAD patients with coronary angiography (CAG) conifrmed diagnosis in our hospital from 2014-01 to 2014-09. According to the value of eGFR, the patients were classiifed into 2 groups:CAD+ CKD- group,n=257 patients with eGFR ≥ 90 ml/(min?1.73 m2), including 182 male and 75 female at the mean age of (60.39 ± 11.09) years, and CAD+CKD+ group,n=166 patients with eGFR < 90 ml/(min?1.73 m2), including 107 male and 59 female at the mean age of (65.80 ± 10.84) years. The patients were treated either by aspirin 0.1 g/d with clopidogrel 75 mg/d for at least 7 days, or by PCI operation with the load of aspirin 0.3g and clopidogrel 300 mg. The thrombelastography was conducted to examine and compare the inhibitory rates of ADP receptor and arachidonic acid (AA) pathway in platelet between 2 groups. Results: The inhibitory rate of platelet ADP receptor in CAD+CKD- group (64.9 ± 27.2) % was higher than that in CAD+CKD+ group (56.6 ± 27.4) %,P=0.039. Based on clinical standard of platelet’s ADP and AA inhibitory rates, in CAD+CKD- group, there were 24/257 (9.4%) of patients only insensitive to clopidogrel, in comparison with 25 (9.7%) of patients only insensitive to aspirin,P=0.99. While in CAD+CKD+ group, there were 21/166 (12.7%) of patients only insensitive to clopidogrel, in comparison with 11 (6.6%) of patients only insensitive to aspirin,P= 0.045. Conclusion: Clopidogrel has decreased effect on anti-platelet therapy in CAD patients combining with CKD, such patients have reduced sensitivity to relevant medication.
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OBJECTIVE: To investigate the feasibility of using thromboelastogram (TEG) to guide the use of antiplatelet drugs in patients undergoing percutaneous coronary intervention (PCI). METHODS: A retrospective study was performed with 349 patients undergoing PCI from January 2011 to April 2011. According to whether measured platelet reactivity by TEG or not,patients were divided into experimental group and control group. Patients of the two groups were all given aspirin plus clopidogrel. Each group was divided into two subgroups according to the doses of antiplatelet drugs; group A used aspirin 100 mg plus clopidogrel 75 mg, and group B used aspirin 300 mg plus clopidogrel 75 mg. A 6-month follow-up was carried out to examine the incidences of bleeding and ischemic events. RESULTS: The incidences of bleeding and ischemic events in the experimental group were significantly decreased compared with those in the control group. The inhibition rates of AA and ADP were significant higher in group B than those in group A of the experimental group. CONCLUSION: Adverse events can be reduced by measuring platelet reactivity by TEG and adjusting antiplatelet drugs.
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Objective:To explore the effect of sarpogrelate on platelet function in patients at the bridging stage before coronary artery bypass grafting (CABG). Methods: A total of 40 consecutive patients with peripheral artery stent and scheduled for CABG in our hospital from 2011-05 to 2013-04 were enrolled in this study. The patients were randomly divided into 2 groups, Low molecular weight heparin (LMWH) alone group, n=19 and Sarpogrelate+LMWH group, n=21. The medications started at 5-7 days before CABG and stopped at 24 h before CABG. The platelet inhibition rates (platelet aggregation induced by collagen+ serotonin) were examined and compared between 2 groups at the baseline (before randomization), 24h and 1h before CABG respectively. Results: The platelet inhibition rates were similar between 2 groups at the baseline (87.33 ± 6.82) % vs (86.11 ± 6.87) %, P=0.577 and 1h before CABG (62.60 ± 12.39) % vs (56.19 ± 14.99) %, P=0.148. At 24h before CABG, the platelet inhibition rate in Sarpogrelate+LMWH group was higher than that in LMWH alone group (83.87 ± 8.99)%vs (63.13 ± 10.88)%, P Conclusion: Sarpogrelate + LMWH may result better platelet inhibition rate with quicker recovery of platelet function upon the medication stopping, which might be a feasible management in patients at the bridging stage before CABG.
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BACKGROUND: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS. METHODS: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed. RESULTS: A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value<0.0001). CONCLUSIONS: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome/complications , Aryl Hydrocarbon Hydroxylases/antagonists & inhibitors , Asian People/genetics , Diabetes Complications , Drug Resistance , Genotype , Platelet Aggregation Inhibitors/blood , Polymorphism, Genetic , Republic of Korea , Ticlopidine/analogs & derivativesABSTRACT
@#ObjectiveTo investigate the platelet inhibition ratio by thromboelastography (TEG) and its clinical impact in patients undergoing percutaneous coronary intervention (PCI). Methods118 PCI patients were divided into ischemic events group (22 cases) and nonischemic events group (96 cases) according to their clinical follow-up of 6 months. Platelet inhibition ratio was measured by TEG. ResultsADP-induced platelet inhibition ratio of ischemic events group decreased significantly compared with nonischemic events group (P<0.01). And there were no significant differences in AA-induced platelet inhibition ratio between two groups (P＞0.05). ConclusionThere may be some relationship between the ischemic events of PCI patients and their drug resistance to clopidogrel.