Association of α_(2A)-Adrenergic Receptor Genetic Variants with Platelet Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing Percutaneous Coronary Intervention

Objective The alpha 2A-adrenergic receptor gene （ADRA2A） polymorphism in individuals antiplatelet response to sympathetic stimulation. The aim of this study was to investigate ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy undergoing percutaneous coronary intervention （PCI）. modifies the the effect of （DAPT） after Methods From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms （SNPs） of ADRA2A gene （rs11195419, rs3750625, rs13306146, and rs553668） and CYP2C19^＊2 were detected by ligase detection reaction （LDR）, and adenosine diphosphate （ADP） inhibition was detected by thromboelastography （TEG）. Results The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 （adjusted P = 0.022） and rs3750625 （adjusted P = 0.016）. The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 （P = 0.033）, rs3750625 （P = 0.020） and CYP2C19＂2 （P = 0.002） were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 （P = 0.003） and rs3750625 （P = 0.002） were significantly associated with ADP inhibition in males, but not in females. Conclusion ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.

Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: In vivo and in vitro studies

AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo , S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150 000/μL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFα, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150 000/μL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen. CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.

Effects of lornoxicam combining with fentanyl on postoperative arrhythmia and platelet function in patients with coronary artery disease after abdominal surgery

To investigate the effects of patient-controlled intravenous analgesia (PCIA) with lornoxicam and fentanyl on arrhythmia and the expression of platelet membrane glycoproteins in patients with coronary artery disease (CAD) after abdominal surgery.Methods Eighty ASA Ⅱ or Ⅲ patients with CAD aged 51～66 yrs weighing 59～68 kg presenting for abdominal surgery participated in this study.CAD was diagnosed by clinical symptoms and ischemic changes on ECG.The patients were premedicated with intramuscular henobarbital 0.1 g and scopolamine 0.3 mg.Anesthesia was induced with fentanyl,droperidol,propofol and vecuronium and maintained with propofol,fentanyl and vecuronium.The patients received PCIA after operation.The PCIA solution contained fentanyl 0.9 mg and droperidol 5 mg in 100 ml of normal saline (N.S.) in group A (n=40) or lornoxicam 56 mg,fentanyl 0.2 mg and droperidol 5 mg in 100 ml N.S. in group B (n=40).In group A the loading dose was fentanyl 0.05 mg and group B lornoxicam 4 mg.PCIA included a background infusion at 2 ml·h -1 and a bolus of 0.5 ml with a 15 min lock-out.VAS(0=no pain,10= worst pain) was used to measure pain intensity.In addition to BP,HR and SpO2 monitoring ECG was continuously monitored with a Holter monitor after operation.Blood samples were taken from peripheral vein before and 6 h after operation and on the 1st,2nd,7th and 8th postoperative days for determination of the expression of CD 62p ,CD 63 and CD 41 /CD 61 on the platelet membrane,platelet count,prothrombin time (PT) thrombin time (TT) and partial thromboplastin time (PTT).Results The two groups were comparable with respect to sex,age,body weight,severity of CAD,duration of operation and intraoperative blood loss.The patients received no blood transfusion during operation.There was no significant difference in VAS score,platelet count,PT,TT and PTT between the two groups.The incidence of atrial and ventricular premature beat on ECG and the expression of CD 41 /CD 61 ,CD 62p and CD 63 on the platelet membrane were significantly lower in group B than in group A on the 7th and 8th postoperative days(P<0.05 or 0.01).Conclusion Postoperative PCIA with lornoxicam and fentanyl can more effectively reduce the incidence of postoperative arrhythmia in patients with CAD.Suppression of activation of platelets by lornoxicam may contribute to the mechanism.10 refs,3 tabs.

Comparative studies between humans and golden Syrian hamsters via thromboelastography

Background:Thromboelastography(TEG)is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process.Lipid metab-olism disorders are crucial risk factors for thrombosis.The lipid metabolism charac-teristics of hamsters resemble those of humans more closely than mice and rats,and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms.Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical pro-cedures.TEG was employed to evaluate coagulation factor function,fibrinogen(Fib)function,platelet function,and the fibrinolytic system.Methods:The whole blood from hamster or healthy human was isolated following the clinical procedure,and TEG was employed to evaluate the coagulation factor func-tion,Fib function,platelet function,and fibrinolytic system.Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline.Blood routine testing used XN-2000 automatic blood analyzer.Results:TEG parameters revealed that hamsters exhibited stronger coagulation fac-tor function than humans(reaction time[R],p=0.0117),with stronger Fib function(alpha angle,p<0.0001;K-time[K],p<0.0001).Platelet function did not differ signifi-cantly(maximum amplitude[MA],p=0.077).Hamsters displayed higher coagulation status than humans(coagulation index[CI],p=0.0023),and the rate of blood clot dissolution in hamsters differed from that in humans(percentage lysis 30 min after MA,p=0.02).Coagulation analysis parameters indicated that prothrombin time(PT)and activated partial thromboplastin time(APTT)were faster in hamsters than in hu-mans(PT,p=0.0014;APTT,p=0.03),whereas the Fib content was significantly lower in hamsters than in humans(p<0.0001).No significant difference was observed in thrombin time(p=0.1949).Conclusions:In summary,TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters.The platelet function of hamsters closely resembled that of humans,whereas their coagulation function was signifi-cantly stronger.

前列腺素E1对原发性肾病综合征作用初探(英文)

Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.

Effect of Yiqitongyanghuatan Recipe on Experimental Atherosclerosis in Rabbits

In order to investigate the roles of Yiqitongyanghuatan (YQTYHT) recipe in reducing the levels of serum cholesterol and plasma lipid peroxidation(LPO), platelet aggregation function (PAgF) and platelet adhesion function (PAdF), the area of atherosclerotic plague coverage in aorta and the thickness of plague, 32 male Japanese white rabbits were divided into 4 groups. The results showed that the YQTYHT recipe could significantly lower the levels of serum cholesterol and tryglyceride, plasma LPO, and PAgF and PadF. The area of atherosclerotic plague coverage in aorta and the thickness of plague in the YQTYHT fed rabbits were decreased as compared with that in the high cholesterol fed rabbits. The above roles might contribute to the main mechanism of YQTYHT against atherosclerosis.

Impact of CYP2C19＊2 and CYP2C19＊3 Polymorphisms on the Response to Clopidogrel and Running Cost Analyses

We investigated the variability in the PFT （platelet function test） response to CYP2C19 polymorphisms and compared it with the clinical presentation. Furthermore, running cost analyses were done. One-hundred and seventy Saudi Arabian patients who were stable on 75 mg clopidogrel for ≥1 month for various cardiac indications were enrolled. We extracted DNA using the MagNA Pure LC instrument. CYP2C19 genotyping for the alleles, ＊1, ＊2 and ＊3, was conducted by real-time PCR （polymerase chain reaction）. The PFT was carried out by VerifyNow P2Y12 assay for all patients. Clinical events were documented retrospectively for all patients. One hundred and seventeen patients presented with the wild variant 1/1, 19 patients with 1/2, and 34 patients with 2/2. We could not detect ＊3. There was a significant association between different genotyping and percentage inhibitions （P = 0.0002）. 1/1 patients tended to be moderate-to-extensive metabolisers, whereas most of the other patients were slow metabolisers. The cost of doing the PFT was 250 SR （Saudi Riyals）/patient and 200 SR/patient for kits and materials （excluding equipment and labour）. The PFT varied considerably with polymorphisms, but showed no significant associations with clinical symptoms.

A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study of the Effects of Tongxinluo Capsules in Acute Coronary Syndrome Patients with High On-Treatment Platelet Reactivity

Background： High platelet reactivity （HPR） during clopidogrel treatment predicts postpercutaneous coronary intervention （PCI） ischemic events strongly and independently. Tongxinluo capsules （TCs） are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome （ACS） patients with HPR. Methods： This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy （DAPT） with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2YIz reaction units （PRUs） between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. Results： Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction （ 15.8% vs. 24.8%, P = 0.013）, especially among patients with one cytochrome P450 2C 19 loss of function （LOF） allele （χ2 = 2.931, P = 0.047）. The TC group also had a lower prevalence of HPR （33.3% vs. 54.2%, t - 5.284, P 0.022） and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein （hsCRP）, but the composite prevalence ofischemic events did not differ significantly （χ2 = 1.587, P = 0.208）. Conclusions： In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.

Platelet function monitoring guided antiplatelet therapy in patients receiving high-risk coronary interventions

Background Large-scale clinical trials have shown that routine monitoring of the platelet function in patients after percutanous coronary intervention （PCI） is not necessary. However, it is still unclear whether patients received high-risk PCI would benefit from a therapy which is guided by a selective platelet function monitoring. This explanatory study sought to assess the benefit of a therapy guided by platelet function monitoring for these patients. Methods Acute coronary syndrome （ACS） patients （n=384） who received high-risk, complex PCI were randomized into two groups. PCI in the two types of lesions described below was defined as high-risk, complex PCI： lesions that could result in severe clinical outcomes if stent thrombosis occurred or lesions at high risk for stent thrombosis. The patients in the conventionally treated group received standard dual antiplatelet therapy. The patients in the platelet function monitoring guided group received an antiplated therapy guided by a modified thromboelastography （TEG） platelet mapping： If inhibition of platelet aggregation （IPA） induced by arachidonic acid （AA） was less than 50% the aspirin dosage was raised to 200 mg/d; if IPA induced by adenosine diphosphate （ADP） was less than 30% the clopidogrel dosage was raised to 150 mg/d, for three months. The primary efficacy endpoint was a composite of myocardial infarction, emergency target vessel revascularization （eTVR）, stent thrombosis, and death in six months. Results This study included 384 patients; 191 and 193 in the conventionally treated group and platelet function monitoring guided group, respectively. No significant differences were observed in the baseline clinical characteristics and interventional data between the two groups. In the platelet function monitoring guided group, the mean IPA induced by AA and ADP were （69.2＋24.5）% （range, 4.8% to 100.0%） and （51.4＋29.8）% （range, 0.2% to 100.0%）, respectively. The AA- induced IPA of forty-three （22.2%） patients was less than 50% and the ADP-induced IPA of fifty-seven （29.5%） patients was less than 30%; therefore, their drug dosages were adjusted. The TEG was rechecked one to four weeks after PCI, and the results indicated that the IPAs had significantly improved （P 〈0.01）. However, no significant differences were found in the rates of the primary efficacy endpoint. Rates in the conventionally treated group and platelet function monitoring guided group were 4.7% and 5.2%, respectively （hazard ratio： 1.13; P=0.79）. Conclusion An antiplatelet therapy guided by TEG monitored platelet function could not improve clinical efficacy even in ACS patients treated with high-risk complex PCI.

Intensified Antiplatelet Treatment Reduces Major Cardiac Events in Patients with Clopidogrel Low Response： A Meta-analysis of Randomized Controlled Trials

Background：Clopidogrel low response （CLR） is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention （PCI）,and intensified antiplatelet treatments （IAT） guided by platelet function assays might overcome laboratory CLR.However,whether IAT improves clinical outcomes is controversial.Methods：Relevant trials were identified in PubMed,the Cochrane Library,and the Chinese Medical Journal Network databases from their establishment to September 9,2014.Trials were screened using predefined inclusion criteria.Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs.Results：Thirteen randomized controlled trials involving 5111 patients with CLR were recruited.During a follow-up period of 1-12 months,the incidences of cardiovascular （CV） death,nonfatal myocardial infarction （MI）,and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm （relative risk [RR] =0.45,95% confidence interval [CI]：0.36-0.57,P 〈 0.000,01）,whereas bleeding was similar between the two arms （RR =1.05,95% CI：0.86-1.27,P =0.65）.Conclusions：IAT guided by platelet function assays reduces the risk of CV death,nonfatal MI,and stent thrombosis （ST） without an increased risk of bleeding in patients undergoing PCI and with CLR.

Balancing bleeding,thrombosis and myocardial injury:A call for balance and precision medicine for aspirin in neurosurgery

Perioperative management of antiplatelet therapy involves a delicate balancing of the risk of periprocedural blood loss with the cardiovascular and thrombotic risk to the patient.Due to the unique nature of neurosurgery,perioperative bleeding may have devastating consequences and cause major morbidity and mortality.The recommendation to discontinue aspirin prior to major neurosurgical procedures rests upon conventional practice,expert consensus with priority given to avoidance of any major bleed.On the contrary recent prospective data do not support the existence of additional bleeding risk in patients continuing aspirin compared to those who stop aspirin prior to procedure.Patients with cardiova-scular and metabolic comorbidities are increasingly encountered in the operation theatre these days.In these patients,prevention of myocardial injury after non-cardiac surgery(MINS)is an important focus for perioperative risk reduction.Prolonged(≥7 days)cessation of antiplatelets is one of the most important predictors of MINS.This complicated milieu of risks and benefits highlights the difficulty of practicing evidence-based medicine and minimizing harm in patients on aspirin needing neurosurgery.

Subacute coronary stent thrombosis in a patient with angina treated with double antiplatelet drugs for six days

Stent implantation has been a great advance in percutaneous coronary intervention （PCI）, decreasing the frequency of acute closure and restenosis. But stent thrombosis is a severe complication of this therapy regardless of the stent type： bare-metal stent （BMS） and drug-eluting stent （DES）. According to the timing after initial PCI, stent thrombosis is considered as acute when occurring between 0 hour and 24 hours after stent implantation, subacute between 24 hours and 30 days,

THE EFFECT OF LOW DOSE ASPIRIN ON THE PLATELET FUNCTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (AMI)

To assess the optimal dose of aspirin （ASA） in the treatment of AMI, 60 cases of AMI: 1. admitted within 24 hours after onset of illness, 2. ASA not used within one week before, 3. any other drugs influencing the platelet function also not used during the course of study, were randomized into two groups, 30 cases each: one with conventional therapy as control, the other combined with daily oral ASA 100mg. They were matched in sex, age, infarct site and coexistent conditions （hypertension, diabetes mellitus, hyperlipemia, smoking etc.）. The second group was further divided into subgroup I with serum peak CK<1000 U/L and subgroup Ⅱ with serum peak CK>1000 U/L. The parameters of platelet function including plasma TXB/6-keto-PGF, platelet aggregation induced by 5-HT and epinephrine were studied on different days for 3 weeks. Twenty healthy persons were selected for normal value of platelet function.

The impact of different doses of atorvastatin on plasma endothelin and platelet function in acute ST-segment elevation myocardial infarction after emergency percutaneous coronary intervention

Objective To investigate the effects of different doses of atorvastatin on plasma endothelin and platelet function in acute ST-segment elevation myocardial infarction(STEMI)patients after emergency percutaneous coronary intervention(PCI).Methods A total of 120 patients with acute STEMI treated with emergency PCI were enrolled and randomly divided into 20 mg of atorvastatin treatment group(standard group,n=60),and 40 mg of atorvastatin treatment group(intensive group,n=60).

The Relationship Between P-Selectin on Platelet Membrane and Platelet Function in Chronic Cor Pulmonale.

Platelet plays an importent role in thromboembolic diseases. It is demonstrated that recurrent pulmonary embolism may cause pulmonary hypertention. In recent years，P-selectin（granule membrane protein，GMP40）was found to be a surface marker for platelet activation.

Antiplatelet therapy resistance induced subacute coronary stent thrombosis in a patient with acute myocardial infarction

Stent implantation has greatly decreased the frequency of acute closure and restenosis after percutaneous coronary inter-vention (PCI) .But stent thrombosis continues to be observed in approximately 1% to 2% of unselected stent procedures and remains a devastating complication.Herein we present a case of subacute coronary stent thrombosis in a patient with anterior AMI treated with double antiplatelet drugs and low molecular weight heparin.