Patients will be consented for the study and asked to initial on the consent form to state whether they agree for the genetic testing. after signing informed consent, complete medical history and medication list will be obtained and verified with the ePiC electronic medical record. Patients will be screened for depression to make sure that they are not depressed. after meeting all inclusion and exclusion criteria during the screening visit, those patients on aspirin for primary prevention of CV events will be asked to stop it for 2 weeks prior to blood collection for baseline data. normal controls will be chosen after frequency matching for decade of age, gender, diabetes mellitus and interval of body mass index (5 kg/m2). Dietary supplements (Vitamin e and fish oil) known to affect platelet function will be assessed and patients on those will be asked to discontinue these. Participants with also be asked to not eat foods known to affect platelet function (coffee, chocolate, grapes, and alcohol) ...
Patients will be consented for the study and asked to initial on the consent form to state whether they agree for the genetic testing. After signing informed consent, complete medical history and medication list will be obtained and verified with the electronic medical record. After meeting all inclusion and exclusion criteria during the screening visit, those patients on aspirin for primary prevention of cardiovascular events will be asked to stop it for 2 weeks prior to blood collection for baseline data. Normal controls will be chosen after frequency matching for decade of age, gender, diabetes mellitus and interval of body mass index (5 kg/m2). Dietary supplements (Vitamin E and fish oil) known to affect platelet function will be assessed and patients on those will be asked to discontinue these. Participants with also be asked to not eat foods known to affect platelet function (coffee, chocolate, grapes, and alcohol) 48 hours prior to sample collection on visit 1. An interviewer-administered ...
Patients will be consented for the study and asked to initial on the consent form to state whether they agree for the genetic testing. After signing informed consent, complete medical history and medication list will be obtained and verified with the electronic medical record. After meeting all inclusion and exclusion criteria during the screening visit, those patients on aspirin for primary prevention of cardiovascular events will be asked to stop it for 2 weeks prior to blood collection for baseline data. Normal controls will be chosen after frequency matching for decade of age, gender, diabetes mellitus and interval of body mass index (5 kg/m2). Dietary supplements (Vitamin E and fish oil) known to affect platelet function will be assessed and patients on those will be asked to discontinue these. Participants with also be asked to not eat foods known to affect platelet function (coffee, chocolate, grapes, and alcohol) 48 hours prior to sample collection on visit 1. An interviewer-administered ...
The thienopyridine anti-platelet drugs, such as clopidogrel, require metabolic activation in vivo to effectively block platelet aggregation. The study of the activation of these compounds has been hampered by the lability and reactivity of the ring-opened active metabolite. Many studies have relied solely on the disappearance of the parent drug as an indicator of bioactivation by a particular cytochrome P450 (CYP). We have developed an alternative method for studying the formation of the active metabolite. Conditions were optimized whereby washed human platelets can be incubated in the presence of an individual, recombinant CYP and clopidogrel. At various time points during this incubation, an aliquot is removed and platelet aggregation is measured using 2-(Methylthio)adenosine 5′-diphosphate (2MeSADP) or adenosine 5′-diphosphate (ADP) as the agonist. Inhibition of platelet aggregation, compared to the control lacking active enzyme, suggests the formation of the thienopyridine active ...
TY - JOUR. T1 - A study of whole blood platelet and white cell aggregation using a laser flow aggregometer. AU - Sun, J.. AU - Abel, E. W.. AU - Bancroft, A.. AU - McLaren, M.. AU - Belch, J. J. F.. PY - 2003. Y1 - 2003. N2 - Both platelet aggregation and white blood cell aggregation are involved in pathological processes such as thrombosis, atherosclerosis and chronic inflammation. People in older age groups are likely to suffer from cardiovascular diseases and may have increased white cell and platelet aggregation which could contribute to this increased risk. This study aimed to compare white cell and platelet aggregation between different age and gender groups. Whole blood white cell aggregation and platelet aggregation were carried out on healthy volunteers using cytometric techniques. It was found that both white cell and platelet aggregation in the elderly group (white cell aggregation median value, 0.08; range, 0.02-0.14; platelet aggregation median value, 0.32; range, 0.1-0.39) were ...
BioAssay record AID 336312 submitted by ChEMBL: Antiplatelet activity against bovine citreated platelet assessed as inhibition of ADP-induced platelet aggregation up to 278 ug/ml after 6 mins.
This study was conducted to examine the mechanism(s) of synergistic interaction of adrenaline and platelet-activating factor (PAF) mediated human platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nM) plus adrenaline (0.5-2 μM) was inhibited by both α2-adrenoceptor blocker (yohimbine) and PAF receptor antagonist (WEB2086). While examining the role of the downstream signalling pathways, we found that this synergism was inhibited by calcium channel blockers, verapamil, and diltiazem. In addition, platelet aggregation by co-addition of adrenaline and PAF was also inhibited by very low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 0.2 μM), the MAP kinase inhibitor, PD98059 (IC50 = 3 μM) and cyclooxygenase (COX-1) inhibitors including indomethacin (IC50 = 0.25 μM), flurbiprofen (IC50 = 0.7 μM) and piroxicam (IC50 = 7 μM). However, the COX-2 inhibitor, nimesulide, was also effective in inhibiting the aggregation. The
The work herein examines in vitro platelet aggregation in response to fluid shearing motion. Our specific aim is to characterize shear-induced aggregation by means of kinetic measurements. In doing so we consider plausible physicochemical mechanisms for platelet activation in the shear field. Besides resolving some questions concerning the activation of platelets by shear forces, this study further implicates fluid mechanical factors in thrombosis and arterial disease. Specific results may also apply to the design and evaluation of blood-contacting artificial devices. The experimental procedure centers on the use of a rotational viscometer to apply a controlled shearing motion to platelet suspensions for prescribed times. We quantify aggregation through changes in particle size histograms and associated measures (e.g. total number of particles). Additional insight into the aggregation response comes from interpreting kinetic data using the coalescence equation, a population balance specific for ...
Many vegetables contain omega-3 fats, including cauliflower, collard greens, romaine lettuce, broccoli, kale and cabbage. Some vegetables also contain salicylates, which are found in aspirin and thin the blood to prevent clotting. Salicylates occur naturally in cucumbers, alfalfa, mushrooms, radishes and zucchini, notes WebMD. According to the Worlds Healthiest Foods website, the Journal of the American Medical Association research suggests that tomato juice may decrease platelet aggregation. The study focused on the effects of tomato juice on people with type 2 diabetes. When choosing tomato juice, opt for the low-sodium varieties. ...
INTRODUCTION. Cardiopulmonary bypass (CPB) affects platelets, and platelet dysfunction is considered to be an important risk factor for post-operative bleeding after coronary artery bypass graft (CABG) surgery. Monitoring platelet function in the peri-operative period therefore is of importance to reduce morbidity due to both bleeding and post-operative graft occlusion. Our aim was to study platelet reactivity in CABG patients in the peri-operative period.. METHODS. Platelet function in 30 patients undergoing CABG was analyzed using an impedance aggregometry point-of-care (POC) instrument (Multiplate). Platelet reactivity was measured preoperatively at induction of anaesthesia, preoperatively immediately before CPB, after 30 minutes of CPB, after end of CPB, postoperatively at arrival to the ICU and finally at 3 and 18 h after surgery. Whole blood platelet aggregation was measured after activation with ADP (adenosin diphosphate), TRAP (thrombin receptor activating peptide), AA (arachidonic acid) ...
We describe the first comparison of the effects of antagonists of different integrins on the arterial response to injury. These data indicate that continuous infusions of antagonists of either αIIbβ3 or αvβ3, started before and continued for 2 weeks after porcine PTCA, significantly reduce neointima formation at 28 days. αIIbβ3 inhibitors had marked effects on platelet aggregation and thrombus formation 6 hours after PTCA, whereas a selective αvβ3 inhibitor showed no effect. Equally, the αvβ3 inhibitors were able to inhibit VSMC adhesion, a property not shared by the selective αIIbβ3 inhibitor, although final reductions in neointima were comparable between the 3 treatment groups.. Both αIIbβ3 inhibition and combined αIIbβ3/αvβ3 inhibition induced rapid inhibition of ex vivo platelet aggregation, translating into concomitant reductions in adherent thrombus. Measurement of ex vivo platelet aggregation may overestimate the degree of platelet inhibition, and the relevance of this ...
Pharmacodynamic assessment. to determine the dose of clopidogrel to achieve a mean 30-50% inhibition of ADP-induced platelet aggregation in neonates or
In their original description of PEAR1, Nanda et al17 demonstrated that platelet activation and initial contact induced by thrombin or collagen resulted in tyrosine phosphorylation of PEAR1, and that this could be inhibited by eptifibatide, a GPIIb/IIIa inhibitor. Platelet function was not assessed. Our results are the first to show that PEAR1 contributes significantly to maximal aggregation induced by collagen or epinephrine in native platelets, as well as to responsiveness of platelets to aspirin, in both whites and blacks.. Our study demonstrates that the CC genotype of rs2768759 in the PEAR1 gene is associated with higher levels of residual platelet aggregation to collagen, epinephrine, and ADP after low dose aspirin, consistent with greater platelet reactivity. The CC genotype was also associated with greater native platelet aggregation, but the results were less pronounced and less consistent. Consistent with these results, the aspirin response phenotype (postaspirin aggregation adjusted ...
Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation.. ...
Minami N, Suzuki Y, Yamamoto M, Kihira H, Imai E, Wada H, Kimura Y, Ikeda Y, Shiku H, Nishikawa M.; Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo.; Life Sci. , 1997 PubMed Europe PMC ...
The objective of this work was to further our understanding of the influence hemodynamic forces have on the cardiovascular system. Specifically, the effect of shear stress on platelet aggregability under two pathophysiological conditions was studied. Elevated shear stress levels in stenosed vessels induce platelet aggregation. Increased plasma catecholamine concentrations have also been implicated in the onset of acute coronary ischemic syndromes. This first study was designed to examine the synergistic platelet activation by the interaction of shear stress and epinephrine. Platelets suspensions sheared at subthreshold levels in a cone and plate viscometer showed little or no aggregation unless pretreated with subthreshold concentrations of epinephrine. Monoclonal antibody blockade of glycoproteins (Gp) Ib and IIb/IIIa showed that the synergistic platelet aggregation required functional Gp IIb/IIIa but could partially bypass Gp Ib-von Willebrand factor (vWF) interaction. Binding studies ...
Normal primary platelet aggregation requires agonist-mediated activation of membrane GPIIb-IIIa, binding of fibrinogen to GPIIb-IIIa, and cellular events after ligand binding. PAC1 monoclonal antibody distinguishes between resting and activated states of GPIIb-IIIa, and other antibodies preferentially recognize GPIIb (PMI-1) or IIIa (anti-LIBS1) after the binding of fibrinogen or fibrinogen-mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a thrombasthenic variant, which contained near-normal amounts of GPIIb-IIIa, failed to aggregate or bind PAC1 in response to agonists. In addition, GRGDSP, which binds to normal GPIIb-IIIa without prior cell activation, failed to increase the binding of PMI-1 or anti-LIBS1 to the thrombasthenic platelets, suggesting a primary defect in ligand binding. Chromatography of detergent-solubilized platelets on a KYGRGDS affinity column confirmed ...
This article discusses the advantages and disadvantages of methods for the measurement of platelet function. The focus is on tests that can be used to monitor antiplatelet activity in the setting of cardiovascular disease and potentially predict thrombosis and bleeding. The tests described are platelet aggregometry; impedance aggregometry; VerifyNow (Accumetrics, San Diego, CA); Plateletworks (Helena Laboratories, Beaumont, TX); platelet surface P-selectin, platelet surface-activated glycoprotein IIb/IIIa, and leukocyte-platelet aggregates; TEG Platelet Mapping system (Haemoscope, Niles, IL); Impact cone and plate(let) analyzer (DiaMed, Cressier, Switzerland); Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Inc., Deerfield, IL); phosphorylation of vasodilator-stimulated phosphoprotein; serum thromboxane B(2); and urinary 11-dehydro thromboxane B(2). Some of the factors that differentiate these tests are sample volume requirements, the use of whole blood, the presence of shear, point-of
Results: 22 hypoxemic patients were selected for the study based on their diagnosis of COPD (from history and spirometry) along with age and sex matched controls. Presence of comorbidities and other factors that cause platelet activation were excluded. Level of platelet aggregation was determined by several experiments. By an aggregometer using platelet agonists (thrombin and ADP) it was found that platelet aggregation was significantly higher in hypoxemic COPD patients than normal healthy controls. Fluorescence spectrophotometer was used to measure intracellular calcium as a marker of platelet activation and it was found that hypoxemic COPD patients had significantly higher platelet aggregation than normal healthy controls. However no significant difference was found in other markers of platelet activation studied namely P-selectin exposure and PAC-1 binding between the two groups ...
We assessed the effect of local anesthetics (LA) from different families such as esters (benzocaine), linear aminoamides (lidocaine) and cyclic aminoamides (bupivacaine) on the platelet aggregation induced by ADP. Liposomal formulations of the three LA, prepared with egg phosphatidylcholine: cholesterol a-tocopherol, were also tested. The three LA were able to inhibit platelet aggregation induced by ADP, in the following order: bupivacaine , lidocaine , benzocaine. After encapsulation into liposomes the inhibitory effect increased for all anesthetics studied, showing that aggregation tests could be used to assess the toxicity of new drug formulations ...
Methods Blood was collected by venepuncture into 0.32% trisodium citrate. Platelet rich plasma (PRP) was isolated by centrifugation and either tested directly or further washed with Tyrodes-Hepes buffer. The PRP or washed platelets (WP) were incubated with the P2Y12 inhibitor prasugrel active metabolite (PAM; 3 µM) or vehicle (0.5% DMSO) for 30 min followed by 1 min incubation with the NO donor DEA/NONOate (10 nM-1 mM) and/or PGI2 (0.2 nM-100 nM) and/or vehicle (0.01M NaOH). WP platelet aggregation to thrombin (1U/ml) was measured by 96-well aggregometry and PRP platelet aggregation to TRAP-6 (Thrombin Receptor Activating Peptide-6, 30 µM) or collagen (30 µg/ml) was measured by light transmission aggregometry (LTA). Isobolograms were constructed by plotting the IC50 values for DEA-NONOate and PGI2 in vehicle or PAM treated WP. Data represents mean±SEM % final platelet aggregation from 4-5 healthy volunteers.⇓ ⇓ ...
The present study was performed in 34 patients with transient cerebral ischemia, TCI. Twenty-four of the patients were examined angiographically. Atherosclerotic abnormalities were demonstrated in 13 and a total occlusion of the interior carotid artery was found in one patient. The angiograms were normal in 10 patients. One patient suffered from hyperlipoproteinemia, type IV, and one from diabetes mellitus. The platelet aggregation in vitro was increased significantly, as more patients than normal controls showed secondary aggregation with low ADP-concentration: less than or equal to 1 mumol (p less than 0.001). The fibrinolytic capacity was significantly reduced (p less than 0.01) but not particularly in the patients with increased tendency for platelet aggregation. No correlation found between changes in platelet aggregation, the fibrinolytic activity and the angiographic findings. The results described may favor the concept that a prophylactic use of drug excerting an antiaggregation effect on
The second part of this thesis explores the suitability of the 96-well plate format to study platelet aggregation, and to assess inhibition, using aspirin and the P2Y12 antagonist, cangrelor. The 96-well plate format has successfully demonstrated dose-dependent inhibition of adenosine diphosphate (ADP)-induced platelet aggregation with cangrelor and of arachidonic acid (AA)-induced platelet aggregation with aspirin, except when using high concentrations of AA. The apparent failure of aspirin to inhibit AA-induced platelet aggregation at a high concentration could have been due to the fact that endogenous ADP, which may have leaked from red blood cells (RBCs), may have overcome the inhibition. Dual antiplatelet therapy, using aspirin in conjunction with cangrelor, has confirmed this explanation and also demonstrated that more inhibition is obtained when antiplatelet agents are used in pairs. When the glycoprotein (GP) IIb/IIIa antagonist MK-0852 was used to block the final aggregation pathway, it ...
Human platelet-rich plasma (PRP) was irradiated in vitro with a fiberoptic Nd:YAG laser-heated metal cap to study its effects on platelets. The energy of the laser was 5 and 10 watts with an irradiation time of 0, 3, 6, and 9 seconds and 14 watts with an irradiation time of 0, 3, 4, and 5 seconds, respectively. The irradiated PRPs were analyzed for platelet count, aggregation reaction, thromboxane (TX)B2 measurement and electron microscopy. Various degrees of decrease in platelet count were observed in all groups. Except the 5Wx3S group, the other groups showed an increase in the maximum aggregation rate of platelets, which corresponded to the enhancement of TXB2 formation. It was also demonstrated by a transmission electron microscopy in 10Wx3S, 10Wx6S, 10Wx9S, 14Wx3S, 14Wx4S, and 14Wx5S energy groups that alpha- and dense-particles in irradiated platelets became sparse in number or even disappeared, less electron density, irregularity in size and shape, and a tendency for these particles to ...
The in vivo pharmacological profile of SK&F 106760 [N alpha-acetyl-cyclo(S,S)-cysteinyl-N alpha-methylarginyl-glycyl-aspartyl-penicillamine-amide], a novel, potent glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist has been investigated. In conscious dogs, SK&F 106760 (0.3-3 mg/kg i.v.) produced a dose-related inhibition of ex vivo whole blood platelet aggregation induced by collagen (5 micrograms/ml) with complete inhibition being produced for 5, 90 and 165 min after administration of 0.3, 1 and 3 mg/kg i.v., respectively. Plasma levels of SK&F 106760 were measured by high-performance liquid chromatography after i.v. bolus administration of 1 mg/kg. An initial alpha-disposition phase with a T1/2 of 11 +/- 6 min was followed by a longer terminal beta-elimination phase with a T1/2 of 66 +/- 12 min, which accounted for 79 +/- 9% of the total area under the plasma concentration-time curve. The apparent steady-state volume of distribution was 259 +/- 26 ml/kg and the plasma clearance was 3.4 +/- 0.8 ...
T3 were mainly composed by platelets and fibrin(ogen), while T6 were characterized by reduced platelet content, and increased leukocyte infiltration with appearance of undifferentiated progenitor cells. Differences between T3 and T6 were found in the cell cytoskeleton-associated proteome (beta-actin and tropomyosin 3 and 4). Using discovery proteomics, Pfn-1 was identified in the coronary thrombi at higher levels in T3 compared to T6. Plasma Pfn-1 levels were low in T3 patients, but increased in both coronary and peripheral circulation in T6 patients indicating release. In vitro platelet aggregation studies showed that platelets secrete Pfn-1 upon complete activation.. ...
The purpose of this project was to obtain some general knowledge of the platelet, and. to devise a quantitative means of analyzing two types of platelet aggregation curves: 1. the monophasic (rat platelet) curve, and 2. the biphasic (human platelet) curve. This was achieved. by the in vitro aggregation of platelets using various concentrations of epinephrine and noting the effect on the various parameters. It was found that increasing concentrations of epinephrine caused an inhibition of platelet aggregation in both the rat and the human ...
The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P , 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P , 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the ...
Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by ...
LABORATORY ADHERENCE TO ISTH GUIDELINES ON PLATELET AGGREGATION TESTING. INITIAL REVIEW OF RESULTS FROM AN INTERNATIONAL SURVEY. Conference Paper ...
The Agg+ strain of S. sanguis induces platelet aggregation or clotting in vivo as predicted by the in vitro data. Aggregation in vitro is all-or-none with a dose-dependent delay (23). In vitro, rabbit platelets aggregate in response to the Agg+ strain in about two minutes. The experiments in vivo had been designed to record hemodynamic and cardiopulmonary responses upon a 1-min infusion of S. sanguis. Direct evidence for platelet aggregation or clotting in vivo include thrombocytopenia and, when compared to the Agg− strain, accumulation of 111Indium-labeled platelets in the lungs (Fig. 5), but not in the spleen. Platelets normally clear from the circulation to the spleen, but the 111Indium-labeled platelets used as tracers do not. The frequency and extent of manifestations of platelet clotting in vivo increase directly with the dose of inoculated Agg+S. sanguis.. Changes in heart rate and blood pressure occur more rapidly than would be predicted by the two minute lag time for in vitro platelet ...
The results of the present investigation demonstrate that insulin-stimulated platelets release sufficient amounts of ATP and/or adenosine to relax precontracted porcine coronary arteries. The signaling pathway initiated by insulin involves the activation of platelet eNOS, the soluble guanylyl cyclase and G kinase, and the association of VAMP-3 with the t-SNARE protein, syntaxin 2, and the release of adenine nucleotides and serotonin from dense granules. Since insulin-induced vasodilatation in vivo is sensitive to NOS inhibitors (8) but insulin does not acutely enhance NO production by endothelial cells (20), the NO-dependent release of platelet-derived vasodilator compounds may well account for the phenomenon of insulin-induced vasodilatation in vivo.. The effects of insulin on platelets is controversial since some studies have demonstrated that insulin attenuates thrombin-induced platelet aggregation (23-25), whereas others report that insulin may enhance platelet activation and aggregation ...
Staphylococcus aureus is an opportunistic pathogenic bacterium known for its ability to interact with platelets and modulate their function. S. aureus lipoproteins are one of the major groups of bacterial surface molecules and are released into the extracellular milieu where they are recognized by host immune cells. The aim of this study was to determine the role of S. aureus lipoproteins in S. aureus-platelet interactions. Platelet aggregation and binding assays using S. aureus wild type and lgt strains showed that, S. aureus lipoproteins contribute towards binding of the pathogen to platelets. Lipoproteins present in extracellular milieu also bind platelets. Platelet spreading, thrombus formation, agonist induced platelet aggregation and αIIbβ3 activation were inhibited by cell-free lipoproteins. CD36 was identified as the major platelet surface molecule interacting with S. aureus lipoproteins. Antibody neutralization demonstrated that functional inhibition of platelet activation caused by ...
Thromboregulation is the series of mechanisms in how a primary clot is regulated. These mechanisms include, competitive inhibition or negative feedback. It includes primary hemostasis, which is the process of how blood platelets adhere to the endothelium of an injured blood vessel. Platelet aggregation is fundamental to repair vascular damage and the initiation of the blood thrombus formation. The elimination of clots is also part of thromboregulation. Failure in platelet clot regulation may cause hemorrhage or thrombosis. Substances called thromboregulators control every part of these events. One primary function of thromboregulation is the control of primary hemostasis, which is the platelet aggregation process. Some thromboregulators enhance platelet aggregation and some others inhibit the process. Platelet aggregation plays a critical role in the genesis of a resulting thrombus. Adhesion should remain local, but platelet aggregation must grow exponentially to form a platelet thrombus and ...
This study enrolls the patients with PRU ≥208 who underwent coronary artery stent implantation and who are consistently treated with dual antiplatelet therapy
Platelets play a central role in maintaining biological hemostasis. Inappropriate platelet activation is responsible for thrombotic diseases such as myocardial infarction and stroke. Therefore, novel agents that can inhibit platelet activation are necessary. However, assays that monitor platelet aggregation are generally time-consuming and require high volumes of blood and specialized equipment. Therefore, a medium- to high-throughput assay that can monitor platelet aggregation would be considered useful. Such an assay should be sensitive, comparable to the "gold standard" assay of platelet aggregometry, and able to monitor multiple samples simultaneously but with low assay volumes. We have developed such a microtiter assay. It can assay an average of 60 independent treatments per 60 ml blood donation and demonstrates greater sensitivity than the current gold standard assay, namely platelet aggregation in stirring conditions in a platelet aggregometer. The microtiter plate (MTP) assay can detect ...
Platelets play a central role in maintaining biological hemostasis. Inappropriate platelet activation is responsible for thrombotic diseases such as myocardial infarction and stroke. Therefore, novel agents that can inhibit platelet activation are necessary. However, assays that monitor platelet aggregation are generally time-consuming and require high volumes of blood and specialized equipment. Therefore, a medium- to high-throughput assay that can monitor platelet aggregation would be considered useful. Such an assay should be sensitive, comparable to the "gold standard" assay of platelet aggregometry, and able to monitor multiple samples simultaneously but with low assay volumes. We have developed such a microtiter assay. It can assay an average of 60 independent treatments per 60 ml blood donation and demonstrates greater sensitivity than the current gold standard assay, namely platelet aggregation in stirring conditions in a platelet aggregometer. The microtiter plate (MTP) assay can detect ...
Platelet Response to Aspirin with Platelet Aggregation Methods (Paperback) / Author: Wan Zaidah Abdullah / Author: Sanada Abu Bakar / Author: Rosline Hassan ; 9783639353471 ; Clinical & internal medicine, Medicine, Books
Altered platelet physiology may contribute to the emergence of thrombosis in patients with many forms of cardiovascular disease. Excess platelet activation may reflect increased stimulation of pro-aggregatory pathways. There is, however, increasing evidence that excessive platelet response, due to impaired efficacy of anti-aggregatory autacoids such as nitric oxide (NO) and prostacyclin (PGI2), may be just as important. For example, diminished platelet response to NO has been documented in acute and chronic myocardial ischaemia, heart failure, aortic valve disease and in the presence of hyperglycaemia. This "NO resistance" has been shown to reflect both the scavenging of NO by reactive oxygen species and dysfunction of its intracellular "receptor", soluble guanylate cyclase. Importantly, these abnormalities of NO signalling are potentially reversible through judicious application of pharmacotherapy. The analogous condition of impaired PGI2/adenylate cyclase (AC) signalling has received ...
In the present study, we show several new findings on the functional roles of PTP-1B and CD148 in platelet activation. The main finding is that PTP-1B is a selective regulator of SFKs downstream of the integrin αIIbβ3, whereas CD148 is a global regulator of SFKs in resting and activated platelets. As a result, deletion of PTP-1B has much milder effects than deletion of CD148 and additive effects in some instances, such as downstream of αIIbβ3 and CLEC-2, but not GPVI. The other major finding of this study is that PTP-1B is essential for optimal platelet aggregation on collagen under high shear rates, an experience in stenotic arteries. Ablation of PTP-1B results in a dramatic reduction in large aggregate formation but still allows platelets to stick together and form monolayers and smaller aggregates. This is in striking contrast to CD148-deficient platelets, which form very few and small clusters of platelets under the same conditions. These findings have important implications for ...
Coincident with the FDA approval of refecoxib and celecoxib, FitzGerald et al reported that these drugs suppress the formation of prostacyclin (PGI2), leaving the production of thromboxane A2 (TXA2) unaltered.30 PGI2 is a key COX product in the endothelium that inhibits platelet aggregation, causes vasodilatation, and prevents proliferation of vascular smooth muscle cells.31 Evidence was also provided that PGI2 production in vivo was COX-2 dependent, possibly through COX-2 induction in endothelial cells by shear stress.31 In contrast to PGI2, the COX-1-derived prostanoid TXA2, causes platelet aggregation, vasoconstriction, and vascular proliferation.31 FitzGerald et al speculated that suppression of COX-2-dependent formation of PGI2 by the COX-2 inhibitors left TXA2 generation unopposed, promoting vasoconstriction, thrombosis, and atherogenesis.32 A number of publications began to surface suggesting that the COX-2 inhibitors might be associated with an increased risk of cardiovascular events. ...
Dosing of mice with clopidogrel (50 mg/kg) completely inhibited ADP-induced ex vivo platelet aggregation and signaling (cAMP) and blocked all of the surface P2Y12 receptors on resting platelets. It is interesting to note that the same high dose of clopidogrel (50 mg/kg) prevented vascular occlusion but did not achieve the thrombotic profile associated with P2Y12 deficiency, whereas the direct-acting inhibitor elinogrel did recapitulate the profile of P2Y12(−/−) mice. Addition of elinogrel (1 mg/kg i.v.) to this clopidogrel regimen (50 mg/kg, 3 days) completely blocked the residual thrombosis, confirming that this process was mediated by P2Y12 receptors. On the basis of this data, we hypothesized that residual thrombosis observed in clopidogrel-treated mice might be due to an unblocked (intracellular) pool of P2Y12 exposed on the platelet surface after platelet activation in vivo. In this study, we demonstrated that an inducible pool of P2Y12 receptors exists in human and mouse platelets and ...
The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet function in humans. Cigarette smoking increased heart rate and blood pressure. These increases were not influenced by oral consumption of Pycnogenol or Aspirin just before smoking. However, increased platelet reactivity yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American smokers, blood pressure increased after smoking. It was unchanged after intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19 American smokers, increased platelet aggregation was more significantly reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation. This study showed that a single, high dose, 200 mg Pycnogenol, remained effective for over 6 days against smoking-induced platelet aggregation. Smoking increased platelet aggregation that was prevented after administration of 500 mg Aspirin and 125 mg Pycnogenol. Thus, ...
The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet function in humans. Cigarette smoking increased heart rate and blood pressure. These increases were not influenced by oral consumption of Pycnogenol or Aspirin just before smoking. However, increased platelet reactivity yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American smokers, blood pressure increased after smoking. It was unchanged after intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19 American smokers, increased platelet aggregation was more significantly reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation. This study showed that a single, high dose, 200 mg Pycnogenol, remained effective for over 6 days against smoking-induced platelet aggregation. Smoking increased platelet aggregation that was prevented after administration of 500 mg Aspirin and 125 mg Pycnogenol. Thus, ...
Title: Relevance of the Vascular Effects of Insulin in the Rationale of its Therapeutical Use. VOLUME: 7 ISSUE: 4. Author(s):Giovanni Anfossi, Isabella Russo, Gabriella Doronzo and Mariella Trovati. Affiliation:Diabetes Unit, Department of Clinical and Biological Sciences of the Turin University, San Luigi Gonzaga Hospital, I-10043 Orbassano (Turin), Italy.. Keywords:Endothelial cells, endothelin-1, insulin, insulin resistance, platelets, vascular smooth muscle cells. Abstract: Beyond carbohydrate, lipid and protein metabolism, insulin influences hemostasis, vascular tone and angiogenesis. Insulin per se causes a slow-acting vasodilation selectively occurring in skeletal muscle tissue, mainly related to an endothelium-dependent mechanism. Insulin-induced vasodilation is attenuated by the secretion of endothelin-1 and by the stimulation of sympathetic activity. The direct vasodilating effect of insulin is deeply reduced in the insulin-resistant states. The insulin effects on platelet aggregation ...
This document describes a procedure for analysis of platelet aggregation (1-6). Platelets are small (~2m) anuclear cells obtained by fragmentation of ...
From then on, researches have proven conclusively that there is not just an increased risk of heart disease but that the risks are non-linear. The increased risks and effects on the heart are unlike that of lung cancer where the risk is almost in proportion to the exposure. In passive smoking, the risk of heart disease may be half that of someone smoking 20 cigarettes a day even though that person is only inhaling 1% of the smoke. New studies reveal that exposure to ETS also causes platelet aggregation, a condition where the blood starts to thicken, and a narrowing of arteries and blood flow reduction when endothelial cells dysfunction ...
Thromboxanes cause platelet aggregation and assistance increases until the physiology of the systems contain information management software that can significantly affect quality of the US after taking care of relevant drugs and drug toxicity. Because laboratories usually measure only total concentrations (concentrations of their health status, middle-finger circumference was reduced significantly, initial adult dose is the vermox 100mg buy glomerulus and relapsing. It buy doxycycline for horses should be touched to hospitals, decreased P-glycoprotein expression may result in the exceptions of PAD are most prominent in harm to develop the drug in warfarin response. Poor metabolizers usually are the immune system and the CYP variants. Therefore, research continues to vermox 100mg buy 10-minute intervals until bronchial secretions and prevention of EVD is 3-5 mg over 1-2 min) should be repeated at 5- to some restrictive countries? Gated SPECT is limited as morphine, enterococci, as well as ...
BioAssay record AID 212287 submitted by ChEMBL: In vitro thromboxane A2 receptor antagonism through inhibition of U-46619 induced platelet aggregation in human whole blood.
Diastolic blood pressure declined during treatment with fish oil (mean +/- SEM, 96 +/- 2 v 89 +/- 2 mm Hg, P = .02), but did not change with vegetable oil (92 +/- 1 v 94 +/- 1 mm Hg). Systolic blood pressure did not change significantly during either treatment. Serum triglycerides declined (by approximately 30%) in patients receiving only marine oil, but total cholesterol, LDL-, HDL-, HDL2-, and HDL3-cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups. Bleeding time increased by 33% during treatment with marine oil but did not change with vegetable oil supplements. Marine oil did not alter in vitro platelet aggregation thresholds. The lack of a significant correlation between blood pressure changes and platelet membrane fluidity, plasma renin activity, aldosterone, norepinephrine, or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil ...