共查询到20条相似文献,搜索用时 31 毫秒
1.
Thomas Gremmel Sabine Steiner Daniela Seidinger Renate Koppensteiner Simon Panzer Christoph W. Kopp 《Thrombosis research》2009,124(5):588-591
Background
High on-treatment residual platelet reactivity is associated with an increased risk of adverse events after coronary stenting. Recent data suggest that cigarette smoking might enhance clopidogrel-mediated platelet inhibition. We therefore sought to investigate the influence of cigarette smoking on clopidogrel- and aspirin-mediated platelet inhibition after percutaneous intervention with stent implantation.Patients and methods
Platelet aggregation was assessed by the VerifyNow P2Y12 and aspirin assays in 102 patients on dual antiplatelet therapy 24 hours after peripheral, coronary or carotid artery stenting. Among these, there were 33 nonsmokers, 29 former smokers and 40 current smokers. Patients in the fourth quartile of the VerifyNow assays were considered as patients with high on-treatment platelet reactivity.Results
Current smokers had significantly lower P2Y12 Reaction Units compared with nonsmokers (p = 0.028). Former smokers also had lower adenosine diphosphate (ADP)-inducible platelet aggregation than nonsmokers, but the difference was not significant (p = 0.52). A high on-treatment residual ADP-inducible platelet aggregation was more common among nonsmokers than among current smokers (14 vs 5; p = 0.004). In a multivariate regression analysis smoking was an independent influencing variable for post-treatment ADP-inducible platelet reactivity (p = 0.026). Aspirin-mediated platelet inhibition showed no significant differences between nonsmokers and former smokers or current smokers (p > 0.3).Conclusion
By in vitro testing, cigarette smoking is associated with enhanced clopidogrel- but not aspirin-mediated platelet inhibition. The clinical implications have to be evaluated in large prospective trials. 相似文献2.
Ulrica Alstrm Fredrik Granath Jonas Oldgren Elisabeth Sthle Hans Tydn Agneta Siegbahn 《Thrombosis research》2009,124(5):572-577
Introduction
A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements.Material and Methods
Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay.Results
There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y12 (r = - 0.29, p < 0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p < 0.05) as measured by flow cytometry when platelets were stimulated with 5 µM ADP. VerifyNowP2Y12 was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p = 0.03) and red blood cell transfusion (Spearman r = 0.43, p < 0.01) requirements, although this might be confounded by aprotinin treatment.Conclusion
We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MAADP. There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y12 and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y12 as an instrument to decide bleeding and transfusion risk does not seem helpful. 相似文献3.
Objective
To study the effects of aqueous extract of Ocimum basilicum L (OBL) on platelet aggregation and experimental thrombus.Methods
Platelet aggregation induced by ADP (5 μM) and thrombin (4 UI), and thrombus weight in an arteriovenous thrombosis (AVT) model were tested after 2 weeks treatment with 15, 75 and 375 mg/kg OBL orally in rats, compared to 8.8 mg/kg/day aspirin. AVT was also tested 2 h after 75 mg/kg OBL orally, after 3 and 7 days treatment, and one, three and seven days after the end of a two-week treatment. Analysis was done by ANOVA followed by protected t-tests (Tukey).Results
OBL (15, 75, 375 mg/Kg) dose-dependently inhibits platelet aggregation by ADP and thrombin, with 75 mg/kg/day having approximately the same effect as 8.8 mg/kg/day aspirin. ADP induced aggregation reached 45%, 28% and 18% for OBL, respectively, 15, 75, 375 mg/kg compared to 71% for control and 27% for aspirin (all p < 0.01 except aspirin vs. OBL 75 mg/kg/day p = 0.7). Thrombin-induced aggregation reached 33%, 22%, 21% for OBL, respectively, 15, 75, 375 mg/kg compared to 67% for control and 48% for aspirin (all p < 0.01 except OBL 75 vs. OBL 375 mg/kg/day, p = 1.0). Compared to a control thrombus weight of 48.1 mg (SD 4.9), thrombus weight was 29.4 (3.3), 19.0 (1.9) and 12.3 (1.7) after treatment for 2 weeks with 15, 75 and 375 mg/kg OBL, respectively, and 27.4 (5.3) after 8.8 mg/kg aspirin (all p < 0.001 except aspirin vs. OBL 75 mg/kg/day p = 1.0). Maximum effect of OBL was reached after one week's treatment. The effect subsided between 3 and 7 days.Conclusion
OBL possesses an inhibitory effect on platelet aggregation induced by ADP and thrombin, that is dose-dependent and results in an anti-thrombotic effect in vivo which develops progressively over 7 days and disappears over 3-7 days. The active ingredient now needs to be characterized. 相似文献4.
Dominick J. Angiolillo Piera Capranzano Bhaloo Desai Steven B. Shoemaker Ronald Charlton Martin M. Zenni Luis A. Guzman Theodore A. Bass 《Thrombosis research》2009,124(3):318-322
Introduction
Type 2 diabetes mellitus (T2DM) patients have a variable response profile to the P2Y12 receptor antagonist clopidogrel. P2Y12 receptor signalling promotes platelet procoagulant activity. The aim of this study was to determine if T2DM patients with suboptimal clopidogrel response have greater platelet procoagulant activity compared with optimal responders and evaluate if this can be modulated by enhancing P2Y12 receptor inhibition.Materials and Methods
A total of 50 T2DM patients in a steady state phase of clopidogrel therapy were studied. Suboptimal responders were randomly assigned to standard (75 mg) or high (150 mg) clopidogrel maintenance therapy for one-month. Afterwards, all patients resumed standard therapy. Platelet procoagulant activity assessed by thrombin-induced platelet-fibrin clot formation using thrombelastography (TEG) was determined at baseline, one-month post-randomization, and one-month after resuming standard therapy.Results
In the overall study population, the reaction time (R), a measure of time to initial thrombin induced platelet-fibrin clot formation, and the time to maximum rate of thrombin generation (TMRTG) values were 6.3 ± 1.7 and 7.6 ± 1.9 minutes, respectively. Suboptimal clopidogrel responders (n = 30) had acceleration of R (p = 0.002) and TMRTG (p = 0.002) compared to optimal responders (n = 20). Suboptimal clopidogrel responders treated with a 150 mg dose showed prolongation of R (p = 0.0001) and TMRTG (p < 0.0001), which returned to baseline values after resuming standard dosage. No differences were observed among patients randomized to 75 mg.Conclusions
T2DM patients with suboptimal clopidogrel response have enhanced platelet procoagulant activity compared to patients with optimal response, which can be down-regulated by more potent platelet P2Y12 inhibition using high clopidogrel maintenance dosing. 相似文献5.
Marie Lordkipanidz Chantal Pharand Donald A. Palisaitis Erick Schampaert Jean G. Diodati 《Thrombosis research》2009,124(5):546-553
Introduction
When studying the efficacy of clopidogrel to inhibit platelet aggregation by light transmission aggregometry, technical decisions must be taken prior to assessment or during analysis, including, but not limited to, concentration of agonist to use and timing of the evaluation of the response on the aggregation curve obtained (peak ADP-stimulated platelet aggregation vs. late aggregation). We investigated how some of these technical modalities affected the results of platelet aggregation obtained after clopidogrel administration.Materials and methods
One hundred and twenty stable coronary artery disease patients requiring a diagnostic angiography were recruited prior to pre-treatment with clopidogrel. Blood samples were tested before clopidogrel initiation and immediately preceding coronary angiography using light transmission aggregometry with either 5 or 20 µM of ADP. Aggregation was measured at maximal amplitude (peak), and 5 minutes after agonist addition (late).Results
While measurements of platelet aggregation as either peak or late aggregation were strongly correlated, peak platelet aggregation was significantly higher than late aggregation, by 10.8% and by 10.3% with ADP 5 and 20 µM, respectively. Moreover, the use of ADP 20 µM resulted in less spontaneous disaggregation than 5 µM in the absence of clopidogrel (11.8% and 4.8% with ADP 5 µM and 20 µM, respectively).Conclusions
When assessing platelet aggregation following clopidogrel, measurement of late aggregation after addition of ADP 20 µM should be preferred. Large clinical trials should be conducted to assess which parameter between residual aggregation or inhibition of platelet aggregation by clopidogrel best predicts clinical efficacy of the drug. 相似文献6.
Background
Recently several alternative forms of the original clopidogrel hydrogensulfate (CHS) were spread worldwide. A large amount of such drugs turned out to be clopidogrel besylate (CB). Only three studies, involving healthy volunteers, investigated the antiplatelet effect of CB, whereas its attribute remained unexplored in the case of patients with cardiovascular diseases. This retrospective study aimed to evaluate the difference between the antiplatelet effects of two clopidogrel formulas, CHS and CB, on patients with coronary artery diseases.Methods
Data of 150 patients with previous CHS treatment were investigated. According to the documentations, the CHS therapy was shifted to CB. 94 patients of the selected population received dual antiplatelet therapy, clopidogrel and aspirin. The antiplatelet effects of CHS and CB were compared by ADP induced platelet aggregation measurements using light transmission aggregometry.Results
Irrespective of the therapeutic combinations the performed statistical investigations failed to show significant difference (p = 0.30) between the effect of CB (AGGmaxCB: 27.6 ± 13.7%) or CHS (AGGmaxCHS: 29.0 ± 15.3%) on the ADP induced platelet aggregation. Insignificant deviations were found in both forms of clopidogrel salts, either in the lack (AGGmaxCB : 32.5 ± 14,2%; AGGmaxCHS: 34,0 ± 16,1%; p = 0,29) or in the presence of aspirin (AGGmaxCB: 24.7 ± 12,5%; AGGmaxCHS: 26,0 ± 14,1%; p = 0,31).Conclusion
Our results indicated that both CB and CHS had an identical inhibitory effect on ADP induced platelet aggregation in patients with cardiovascular diseases. Moreover their efficiency showed no overall significant difference in the case of dual antiplatelet therapy with aspirin as well. However there might be an inter- and intraindividual variability between the two clopidogrel formulas. 相似文献7.
Background
It is claimed that in shear-induced platelet function tests, shear-stress is the sole agonist causing platelet activation and resultant thrombosis. However, the fact that red blood cells (RBC) are essential to achieve platelet aggregation in these tests supports recent evidence that ADP makes an important contribution to shear-induced platelet reaction.Aim
To establish the role of ADP in shear-induced thrombosis, and investigate whether a shear-induced thrombosis test can assess ADP-receptor (P2Y12) antagonist medication.Methods
Blood from healthy volunteers was tested using the Global Thrombosis Test (GTT), before and after clopidogrel. To investigate the importance of contact of blood with plastic, the reactive part of the tube was primed with saline. We also investigated the effect of priming the tube with water, to cause localised haemolysis and ADP release.Results
Saline-priming prolonged occlusion times (OT) by 25% (p < 0.01) confirming ADP release from platelets and RBC as a result of contact. Water-priming shortened OT, accelerating the thrombotic reaction (accelerated GTT; aGTT) (OT 379 vs. 177s, p < 0.01). Clopidogrel increased OT (379 vs. 477s, p < 0.01), preventing the shortening of aGTT-OT (177 vs. 362s, pre- and post-clopidogrel; p < 0.01).Conclusion
In addition to thrombin formation, ADP released from platelets and RBC in native blood subjected to high shear-stress makes an important contribution to the resultant thrombotic occlusion. The described aGTT sensitively detected the effect of clopidogrel and thus seems suitable for monitoring and individualizing ADP-receptor antagonist therapy. Parallel measurement of GTT and aGTT would allow assessment of both global thrombotic status and response to P2Y12 antagonist therapy. 相似文献8.
Diego A de Prado AP Cuellas C de Miguel A Samaniego B Alonso-Rodríguez D Bangueses R Vega B Martín J Fernandez-Vazquez F 《Thrombosis research》2012,130(3):e31-e36
Introduction
Thrombolysis, as reperfusion therapy for ST segment elevation myocardial infarction (STEMI), induces a pro-thrombotic status with enhanced platelet activity; this study aims to evaluate P2Y12 platelet reactivity and response to clopidogrel in the post-thrombolysis scenario.Materials and Methods
Observational, prospective study, including consecutive patients with elective angiography after thrombolytic therapy for STEMI. Every patient received antiplatelet therapy with loading doses of 250 mg aspirin and 300 mg clopidogrel on admission followed by 100 mg aspirin and 75 mg clopidogrel daily. P2Y12-dependent platelet reactivity (expressed in P2Y12-Reaction Units, PRU) was assessed with VerifyNow® device on admission, daily after thrombolysis and pre-angiography.Results
41 patients fulfilled the inclusion criteria. Median time between thrombolysis and angiography was 2,5 days (IQR 1,8-4,1). Post-treatment platelet reactivity (PPR) showed poor correlation with time on clopidogrel treatment (r2 = 0.04) and reached a maximum value of 274 ± 84 PRU during the first 24 h after thrombolysis (Day + 1 determination). After this, values showed a progressive reduction until the point of angiography (249 ± 82 PRU), without significant differences between consecutive time-points (p = 0,549).Inhibition of platelet aggregation (IPA) assessed as a percentage of P2Y12 receptor blockage was poor, increasing gradually from 0 ± 4% on admission to 11 ± 6% the day of the angiography (p = 0,001). 71,4% of patients showed PPR ≥ 208 PRU during angiography.Conclusions
Platelet reactivity, as assessed by post-treatment P2Y12 mediated reactivity, is heightened after thrombolytic therapy during STEMI management. In this scenario, standard doses of clopidogrel did not achieve significant inhibition of ADP-mediated platelet reactivity. 相似文献9.
Einor Ben Assayag Shani Shenhar-Tsarfaty Irena Bova Shlomo Berliner Sali Usher Hava Peretz Itzhak Shapira Natan M. Bornstein 《Thrombosis research》2009,124(4):458-462
Introduction
C-reactive protein (CRP) is an inflammatory protein that may play a role in the pathogenesis of atherosclerosis. CRP gene single nucleotide polymorphisms (SNPs) have been shown to be associated with CRP concentration; however, their independent effect on atherosclerosis has not been yet established. We aimed to determine whether the 5′-flanking -757T>C CRP gene polymorphism is associated with CRP concentration and carotid atherosclerosis.Methods
We genotyped the -757T>C CRP gene SNP and determined the concentration of serum CRP, the intima-media thickness (IMT) of the common carotid artery and the existence of plaque/s in 612 apparently healthy men and women aged 66 ± 10 years.Results
Carriers of the CRP -757C allele presented with higher IMT and higher CRP concentrations (p = 0.002, p = 0.042, respectively). After adjustment for vascular risk factors, linear regression analysis showed an independent effect of CRP -757C allele on carotid IMT, beyond serum CRP concentrations. This SNP was also associated with carotid plaque occurrence (O.R. 1.74, 95% CI 1.1-2.77, p = 0.002).Conclusions
The present study provides evidence that a genetic variant of CRP gene is associated with carotid atherosclerosis, independently of traditional vascular risk factors. Further large-scale genomic studies are required, which may identify the genetic vulnerable subjects to develop atherosclerosis. 相似文献10.
Lordkipanidzé M Diodati JG Palisaitis DA Schampaert E Turgeon J Pharand C 《Thrombosis research》2011,128(1):47-53
Introduction
Intersubject variability in platelet response to aspirin could be related to genetic factors that regulate platelet enzymes or receptors. This study evaluates the impact of the selected polymorphisms in the COX-1 gene, the CYP5A1 gene, the P2RY1 receptor gene, and the GPIIbIIIa receptor gene on platelet response to aspirin and risk of suffering from major adverse cardiovascular and cerebrovascular events (MACCE).Materials and methods
192 Caucasian patients with stable coronary artery disease treated with daily aspirin were recruited and followed for 3 years. Platelet aggregation was measured by light transmission aggregometry with arachidonic acid (1.6 mM) and adenosine diphosphate (5, 10 or 20 μM) used as agonists. Genotyping was performed by standard PCR methods.Results
Arachidonic acid-induced platelet aggregation was unaffected by the COX-1 22C/T and by the PlA1/A2 polymorphisms. However, carriers of the 1622 G/G genotype of the P2RY1 gene had significantly higher levels of arachidonic acid-induced platelet aggregation compared with non-carriers (AA 2.0%, AG 2.0% vs. GG 9.0%, p = 0.047). Carrying the 1622 G/G genotype increased the risk of inadequate platelet response to aspirin, defined as arachidonic acid-induced aggregation ≥ 20%, by a factor of 8.5 (1.4 - 53.3, p = 0.022) and the risk of 3-year MACCE by a factor of 7 (1.4 - 34.7, p = 0.017).Conclusion
The 1622A/G mutation of the P2RY1 gene could contribute to inadequate platelet response to aspirin and is associated with an increased risk of suffering from MACCE. 相似文献11.
Raffaele Palmirotta Patrizia Ferroni Annalisa Savonarola Francesca Martini Filippo Ciatti Anastasia Laudisi Valentina Sini Girolamo Del Monte Fiorella Guadagni Mario Roselli 《Thrombosis research》2009,124(4):403-408
Introduction
Plasminogen activator inhibitor (PAI-1) may have an independent prognostic value in breast cancer (BC). PAI-1 4G/5G polymorphism may have significance for antigen expression. Thus, we analyzed the possible associations between PAI-1 4G/5G polymorphism, plasma PAI-1 levels, and clinicopathological features of breast cancer (BC) patients.Patients and Methods
PAI-1 4G/5G polymorphism (both on germinal and tumor DNA) and plasma PAI-1 levels were investigated in 99 BC patients and 50 unrelated healthy women similar for age and menopausal status.Results
No association was found between allele frequencies and clinicopathological features of BC or plasma antigen levels. Plasma PAI-1 levels were higher in BC compared to controls (p = 0.002), particularly in patients with large tumors (p < 0.001). 5-year follow-up was achieved in 79 patients: 30% had relapsing disease, 63% with positive compared to 37% with negative PAI-1 levels (p < 0.05). 5-year relapse-free survival rate of positive PAI-1 was 46% vs., 77% of negative patients (p = 0.02).Conclusions
We may conclude that plasma PAI-1 levels in BC patients could represent a useful prognostic variable for relapse, although PAI-1 polymorphism might not represent a genetic susceptibility factor. 相似文献12.
Introduction
Kidney disease predisposes to cardiovascular events. This study investigated the influence of renal function and platelet turnover on the antiplatelet effect of aspirin in patients with coronary artery disease.Materials and Methods
We included 124 aspirin-treated patients with coronary artery disease and normal to moderately reduced renal function. All tests were performed one hour after aspirin ingestion. Renal function was assessed using creatinine, estimated glomerular filtration rate (eGFR), and cystatin C. The antiplatelet effect of aspirin was evaluated using the VerifyNow® Aspirin assay and multiple electrode aggregometry (MEA, Multiplate®) induced by collagen (1.0 μg/mL) and arachidonic acid (1.0 mmol/L). Von Willebrand factor was measured as a marker of endothelial dysfunction. Platelet turnover was evaluated by measurements of immature, reticulated platelets.Results
Renal function did not influence the antiplatelet effect of aspirin evaluated by MEA (r = − 0.2-0.09, p = 0.03-0.77) or the VerifyNow® (r = − 0.12-0.11, all p-values > 0.1). In contrast, renal function correlated inversely with von Willebrand factor levels (rcreatinine = 0.48, p < 0.0001; reGFR = − 0.46, p < 0.001; rcystatin C = 0.54, p < 0.0001). The number of immature platelets correlated with platelet aggregation according to MEA (r = 0.20-0.39, all p-values < 0.03), but not according to VerifyNow® (r = − 0.07, p = 0.50).Conclusions
A reduced antiplatelet effect of aspirin may be explained by an increased number of immature platelets. Moderately impaired renal function was associated with high levels of von Willebrand factor, but not with a reduced antiplatelet effect of aspirin. 相似文献13.
Zenon Huczek Krzysztof J. Filipiak Janusz Kochman Marcin Michalak Marek Roik Radoslaw Piatkowski Marcin Grabowski Marek Postula Grzegorz Opolski 《Thrombosis research》2010,125(5):406-412
Introduction
Pre-procedural predictors of early stent thrombosis (ST) and future response to platelet inhibitors are in demand. We sought to evaluate the impact of baseline platelet indices on the occurrence of early ST and future residual platelet reactivity.Materials and methods
Hundred and eight patients with acute coronary syndromes (ACS) in whom stents were implanted were included: 36 consecutive ST cases and 72 matched controls. Platelet indices assessed with flow cytometry before stent implantation were retrieved from the department's data base. Residual platelet reactivity specific to aspirin (aspirin reaction units-ARU) and clopidogrel (P2Y12 reaction units-PRU) was assessed prospectively with VerifyNow® under dual antiplatelet treatment.Results
Platelet size reported as mean platelet volume (MPV) or proportion of large platelets (LPLT) was significantly higher in ST cases compared with controls (10.4, 95% confidence intervals [CI], 10.1-10.8 vs. 9.7, CI, 9.5-9.9, P = 0.0004 and 35.8, CI, 34.2-37.3 vs. 33.3, CI, 32.2-34.3, P = 0.007, respectively). Dual aspirin and clopidogrel poor-responsiveness was diagnosed significantly more often in ST cases than in controls (19.6% vs. 1.4%, P = 0.004), whereas no difference was observed for single aspirin or clopidogrel poor-responsiveness. A strong correlation was found between MPV and both, ARU (r = 0.66, P < 0.0001) and PRU (r = 0.55, P < 0.0001). Similarly, higher LPLT was associated with higher ARU (r = 0.47, P < 0.0001) and PRU (r = 0.38, P = 0.0001).Conclusions
Baseline platelet size is increased in patients with ACS developing early ST and correlates with future residual platelet reactivity under aspirin and clopidogrel therapy. Dual but not isolated aspirin or clopidogrel poor-responsiveness appears to be associated with early ST. 相似文献14.
Introduction
Analyses of platelet aggregation in hirudin whole blood using Multiplate® was validated. Reference intervals for the most commonly used agonists were established, and the association between platelet aggregation, age, gender and haematological values was analysed.Material and methods
We included 121 healthy individuals to establish reference intervals and six healthy individuals for evaluation of the day-to-day variation. Platelet aggregation was evaluated on hirudin whole blood employing Multiplate® induced by arachidonic acid, ADP, collagen and ristocetin (RISTOlow and RISTOhigh). Measurements of haematological values were performed employing Sysmex K-4500.Results
We found no association between platelet aggregation and age (p > 0.57 for all agonists, except RISTOlow: p = 0.05). Platelet aggregation was significantly higher in women compared to men for all agonists (p < 0.0003), except RISTOlow (p = 0.05). A reference interval is presented as 95% confidence interval suitable for any age and both sex. Day-to-day variation was < 11% for all agonists except for RISTOlow. No association was found between platelet aggregation and haematocrit or red blood cell count after adjusting for age and gender except for RISTOhigh. A positive significant association was found between platelet count and platelet aggregation (p < 0.04). Finally, a significant positive association was found between platelet aggregation and white blood cell count for all agonists (p < 0.05) except RISTOlow and RISTOhigh (p > 0.05).Conclusion
Reference intervals for platelet aggregation in healthy individuals (age: 17 to 66 years) were established in hirudin whole blood measured by Multiplate® employing the most commonly used agonists. 相似文献15.
Anne Flöck Astrid Zobel Gerhard Bauriedel Christoph Hammerstingl Anna Schuhmacher Georg Nickenig 《Thrombosis research》2010,126(2):e83
Introduction
Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation.Methods
Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting. Depressed patients were randomized to two groups treated either with escitalopram (n = 47) or nortriptyline (n = 44). Platelet aggregation was studied on days 0, 1, 3, 7, 14, 21, 84 of continuing medication and was determined in response to adenosine diphosphate (ADP) and collagen.Results
Platelet aggregation induced by ADP was increased among depressive patients compared with that of healthy controls (26%, p = 0.006). With antidepressant treatment, changes in platelet aggregation remained comparable in both groups at early time points (d1 to 21). In contrast, at day 84, patients with antidepressive response revealed significant differences in both medication groups: Patients receiving escitalopram showed a 23% decrease of ADP induced aggregation (p = 0.03) and a 15% decrease of collagen induced aggregation (p = 0.03). With nortriptyline the increase in impedance was reduced by 29% after ADP induction (p = 0.046).Conclusion
Depressed patients have higher ex vivo platelet aggregation that may contribute to increased cardiovascular morbidity. After three months of antidepressant treatment with either escitalopram or nortriptyline, platelet aggregation was significantly reduced in antidepressant responders, irrespective of the antidepressant medication type. 相似文献16.
Introduction
The antithrombotic effect of the glycopreotein IIb/IIIa (GP IIb/IIIa) receptor antagonist Z4A5, exert alone or combination with heparin, and/or aspirin, was examined in a rabbit arteriovenous shunt thrombosis model.Materials and Methods
Thrombosis was induced by the insertion of a silk thread (thrombogenic substrate) into an extracorporeal shunt. Before and after drug administration (0, 5, and 15 min), ex vivo adenosine diphosphate (ADP)-induced platelet aggregation and coagulation parameters (prothrombin time (PT) and activated partial thromboplastin time (APTT)) were determined in platelet-rich plasma (PRP) and platelet poor-plasma (PPP), respectively.Results
Our data demonstrated that, compared to the control, Z4A5 decreased the thrombus weight (31-65%) in a dose-dependent manner and inhibited ADP-induced platelet aggregation (47-98%) 5 min after Z4A5 administration (25-100 mg/kg). However, PT and APTT remained stable, even at the highest dose (100 mg/kg). Heparin (100 U/kg) and aspirin (15 mg/kg) also significantly reduced thrombus mass, but this effect was accompanied by an increase of APTT by heparin. Furthermore, the combination of heparin (100 U/kg) and a low dose of Z4A5 (25 mg/kg) failed to produce an additional benefit beyond that provided by heparin or Z4A5 alone, whereas Z4A5 (25 mg/kg) plus aspirin (15 mg/kg) potentiated the antithrombotic effects of both compounds without further increasing the values of coagulation.Conclusions
Our results indicate that Z4A5 is an effective antithrombotic agent with no significant effects on values of coagulation. Furthermore, Z4A5 can potentiate these antithrombotic effects when prescribed with aspirin. 相似文献17.
A. Bleakley Chandler Angela D. Earhart Henry E. Speich Teddi J. Kueter Jennifer Hansen Lisa K. Jennings 《Thrombosis research》2010,125(1):44-52
Introduction
The aim of this study was to further characterize the effect of the antiplatelet agents, aspirin and eptifibatide, on the surface expression of CD40L and CD62P on platelets from patients with stable coronary artery disease.Materials and methods
Platelet function was evaluated using standard light transmission aggregometry. Measurements of CD62P and CD40L were carried out by flow cytometry and ELISA assays.Results
All patients had the expected level of platelet aggregation inhibition in response to 20 μM ADP in the presence of increasing eptifibatide concentrations. Platelet activation by adenosine diphosphate (ADP) or thrombin agonist peptide (TRAP) increased CD62P and CD40L surface density in the presence of aspirin by 1.9 - 2.8 -fold. Aspirin treatment did not prevent either CD62P or CD40L expression. Eptifibatide pretreatment at pharmacologically relevant concentrations blocked agonist-induced increases in CD62P platelet surface density. A marked percentage of platelets still expressed low levels of surface CD62P suggesting slight platelet activation even with potent platelet inhibition. Eptifibatide also blocked agonist-induced increases in CD40L surface expression and decreased the percent of platelets positive for surface CD40L. Decreased expression of CD40L was due to an inhibition of CD40L translocation and not caused by enhanced shedding from the surface, as soluble CD40L (sCD40L). Eptifibatide concentrations that effectively blocked platelet aggregation correlated with total inhibition of increased CD62P and CD40L surface density.Conclusion
Blockade of the GPIIb-IIIa receptor on platelets from coronary artery disease patients may have significant bearing on reducing proinflammatory and procoagulant events mediated by CD62P and sCD40L. 相似文献18.
Roger C. Carroll Ronald E. Worthington Carolyn C. Snider Patrick A. Dakin Dale C. Wortham Jason Scott 《Thrombosis research》2010,125(4):e118-1370
Introduction
We have previously defined aspirin resistance detected by TEG PlateletMapping using arachidonic acid (AA). This aspirin resistance is observed as platelet activation (> 20%) by AA in whole blood, even though the isolated platelets are inhibited by aspirin. This platelet activation in whole blood is due to a transcellular pathway mediated by platelets and leukocytes.Methods
To determine if this PlateletMapping assay of aspirin resistance on pre-procedure blood samples correlated with an in vivo response we assayed the first voided urine samples collected 2-8 hours post interventional cardiology procedures for 11-dehydro thromboxane B2.Results and Conclusions
We detected 27 aspirin resistant patients out of a total of 81 (33%), in agreement with our previous study. All of these patients were on aspirin therapy, confirmed by a < 20% aggregation response to AA by light transmission platelet aggregometry using isolated platelet rich plasma. Aspirin resistant patients urine samples (14 out of a total of 60 patients analyzed) contained significantly (P = 0.008) higher 11-dehydro thromboxane B2 levels than the other 46 aspirin sensitive patients urine samples. Since our previous study implicated 12- and 15-lipoxygenases in this pathway, we also assayed for polymorphisms to determine any correlation with aspirin resistance. A correlation was found in a polymorphism affecting the lipoxygenase domain of platelet 12-lipoxygenase. This result indicates that aspirin resistance detected in whole blood by the TEG PlateletMapping assay correlates with a physiological consequence in terms of thromboxane formation. This is the first report of such a correlation. 相似文献19.
Ismail Elalamy Brigitte Tardy-Poncet Agns Mulot Emmanuel de Maistre Claire Pouplard Philippe Nguyen Bndicte Cleret Yves Gruel Thomas Lecompte Bernard Tardy GEHT HIT study group 《Thrombosis research》2009,124(5):554-559
Background
Prognostic factors for unfavorable clinical outcome in patients with heparin-induced thrombocytopenia (HIT) are largely unknown.Design and methods
In this multicenter, retrospective, case-control study, all HIT patients were treated with danaparoid. Study cases were HIT patients with an unfavorable clinical outcome. Controls were HIT patients who were not study cases. Unfavorable clinical outcome was defined as the occurrence of at least one of the following clinical events: death within 60 days after HIT start date, or venous or arterial thromboembolism, amputation, major bleeding, or disseminated intra-vascular coagulation between 48 hours and 60 days after HIT start date.Results
Compared with controls (n = 65), thrombotic episodes within 48 hours of HIT start date were more frequent (59.2% versus 32.3%; p = 0.004), the median time between HIT start date and initiation of danaparoid infusion was longer (3.0 versus 1.0 days; p = 0.001), and this treatment was more frequently underdosed (43.8% versus 18.8%; p = 0.004) in study cases (n = 49). Upon multivariate analysis, all these three parameters were significant predictive factors for unfavorable clinical outcome. The adjusted odds ratios [95% confidence interval] were 6.6 [2.5-17.3] for time between HIT start date and danaparoid initiation over 48 hours, 4.3 [1.5-12.0] for danaparoid underdosing, and 3.2 [1.3-8.0] for presence of a thromboembolic episode at HIT start date.Conclusions
This study supports the recommendations concerning the management of HIT patients, namely discontinuation of all heparin administration once the diagnosis is suspected and prompt initiation of an alternative anticoagulant drug with a strict adherence to doses specifically recommended for these patients. 相似文献20.