Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Platelet Aggregation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources
PubMed1985

Deaggregation of human platelets aggregated by thrombin.

Human platelets that have undergone the release reaction do not deaggregate readily. We examined conditions under which washed human platelets can be deaggregated after they have undergone an extensive release reaction induced by thrombin (1 or 5 U/ml). To make fibrinogen receptors unavailable, either CP/CPK (or apyrase) was used to remove released ADP, or PGE1 was used to increase cAMP. Chymotrypsin was used to digest proteins that might link platelets, and heparin to interact with released proteins and interfere with their binding to platelets and to each other. Individually, none of these caused deaggregation; heparin did not inhibit the effect of thrombin because no antithrombin III was present. Platelets exposed to thrombin (1 U/ml) which was neutralized at 90 sec by hirudin, could be deaggregated by combinations of CP/CPK (or apyrase) and chymotrypsin, or PGE1 and chymotrypsin. When a higher concentration of thrombin was used (5 U/ml) these combinations caused platelets to deaggregate only when heparin was added before thrombin induced the release reaction. Thus, when extensive release occurs three mechanisms may come into play to link human platelets: one that requires the fibrinogen receptor; a heparin-sensitive reaction that may involve the binding of released proteins; and a linkage that can be disrupted only by proteolysis, providing the other two mechanisms are also inhibited.

Blood Platelets↗
PubMed1985

Monoclonal antibody to glycoprotein Ib inhibits both thrombin- and ristocetin-induced platelet aggregations.

A monoclonal antibody named TM60, which inhibited both thrombin- and ristocetin-induced platelet aggregations, was obtained by hybridoma technique. TM60 inhibited binding of von Willebrand factor to platelets under the presence of ristocetin. The subclass of TM60 was IgG2a. TM60 did not inhibit ADP-, collagen-A-23187-, arachidonic acid- and PAF-induced platelet aggregations, but inhibited polylysine-, polybrene- and cationized ferritin-induced platelet aggregations. ATP-release from platelets induced by thrombin was also inhibited by TM60. Immunoprecipitation and SDS-PAGE experiments demonstrated that TM60 recognized an epitope on GPIb whose molecular weight was 165,000 under non-reduced and 145,000 under reduced conditions.

Adenosine Triphosphate↗
PubMed2005

Variability in platelet aggregation following sustained aspirin and clopidogrel treatment in patients with coronary heart disease and influence of the 807 C/T polymorphism of the glycoprotein Ia gene.

A broad variability in patient response to dual antiplatelet treatment has been described during the first month of treatment. Data on platelet function profiles in patients on dual antiplatelet therapy for a more sustained period are limited. Whether gene sequence variations of the glycoprotein Ia/IIa receptor influence platelet aggregation in these patients is also unknown. The aim of this study was to characterize platelet aggregation profiles in patients on dual antiplatelet treatment (aspirin plus clopidogrel) for >1 month and to assess whether these may be influenced by the C807T polymorphism of the glycoprotein Ia gene. We included 82 patients, who were divided into 2 groups: carriers (CT + TT genotypes; n = 51) and noncarriers (CC genotype; n = 31) of the mutant T allele. Platelet aggregation was assessed using light transmittance aggregometry after stimuli with adenosine diphosphate (20 micromol/L), collagen (6 microg/ml), and epinephrine (20 micromol/L). A significant variability in the distribution of platelet aggregation was observed in the overall study population, as well as in carriers and noncarriers of the T allele. T allele carriers had increased platelet aggregation compared with noncarriers after stimuli with adenosine diphosphate, collagen, and epinephrine (p <0.05 for all platelet aggregation assays). Thus, platelet aggregation varied significantly in patients on long-term dual antiplatelet treatment and was increased in T allele carriers of the 807C/T polymorphism of the glycoprotein Ia gene. These findings may contribute to the increased ischemic risk observed in these patients.

Adult↗
PubMed1995

Purification and characterization of the platelet-aggregating sialoglycoprotein gp44 expressed by highly metastatic variant cells of mouse colon adenocarcinoma 26.

A platelet-aggregating sialoglycoprotein with a molecular weight of 44,000 (gp44) was immunochemically purified from highly metastatic mouse adenocarcinoma cells. The rat monoclonal antibody (mAb) 8F11 used in the purification procedure has been generated previously against NL-17 cells derived from the mouse colon 26 cell line, mAb 8F11 inhibits NL-17 cells from inducing platelet aggregation and suppresses their experimental metastasis to the lung. The purified gp44 induced mouse platelet aggregation in a dose-dependent manner without any plasma component. This aggregation was completely inhibited by mAb 8F11. The gp44 was partially characterized by sequential enzymatic hydrolysis of carbohydrates and was found to be O-glycans enriched. When gp44 was sequentially treated with N-glycanase and neuraminidase, it lost platelet aggregation activity. Further treatment with O-glycanase resulted in a loss of the reactivity to mAb 8F11. These results suggest that sialylated carbohydrate chains of gp44 are involved in the induction of platelet aggregation and may play an important role in the colonization of NL-17 cells in the lung.

Adenocarcinoma↗
PubMed1988

Streptokinase-induced, antibody-mediated platelet aggregation: a potential cause of clot propagation in vivo.

The administration of intracoronary streptokinase to a patient with a prior history of rheumatic fever was associated with the retrograde propagation of thrombus from the left anterior descending coronary artery into the left main coronary artery with near catastrophic consequences. The addition of streptokinase to platelet-rich plasma from the patient initiated platelet aggregation and secretion in vitro. Platelet aggregation was also seen in 1 of 15 control subjects after the addition of streptokinase, and the addition of plasma or immunoglobulin G (IgG) from the index patient supported platelet aggregation in the presence of streptokinase in all of the previously nonreactive control subjects. This in vitro platelet aggregation was specific for streptokinase and not initiated by either urokinase or tissue plasminogen activator. Streptokinase-induced platelet aggregation was not inhibited by aprotinin, but was completely attenuated by the addition of an excess of antihuman IgG Fab. These findings suggest that streptokinase can initiate specific antibody-mediated platelet aggregation in vitro and may be more than coincidentally related to clot propagation or thromboembolism in vivo.

Antibodies, Viral↗
PubMed2002

Effect of resveratrol on platelet aggregation in vivo and in vitro.

OBJECTIVE: Low or moderate consumption of red wine has a greater benefit than the consumption of other beverages in the prevention of atherosclerosis and coronary heart disease and this is increasingly attributed to the polyphenol compounds in red wine, such as resveratrol. In the present study, we investigated the effect of resveratrol on platelet aggregation in vitro and in vivo. METHODS: Platelet aggregation in rabbits and normal subjects was measured using Born's method. RESULTS: Resveratrol, at 10 - 1000 micromol/L, significantly inhibited platelet aggregation in vitro induced by collagen, thrombin, and ADP in healthy subjects. The inhibitory effect was concentration-dependent. Hypercholesterolemia induced by high-cholesterol diet enhanced ADP-induced platelet aggregation. Resveratrol 4 mg x kg(-1) x d(-1) inhibited ADP-induced platelet aggregation in vivo despite no changes in serum lipid levels. CONCLUSIONS: Resveratrol inhibits platelet aggregation both in vitro and in vivo. This may be one of the mechanisms by which resveratrol prevents atherosclerosis.

Animals↗
PubMed1990

Effect of nicergoline on platelet aggregation, plasma viscosity and erythrocyte deformability in geriatric patients with cerebral infarction. Preliminary report.

The effects of nicergoline (Sermion) on platelet aggregation, plasma viscosity and erythrocyte deformability were evaluated in 11 geriatric patients with cerebral infarction, 2 men and 9 women (ages 61-78, mean age 71.6). Nicergoline was given orally at a dose of 5 mg 3 times daily after meals for 8 weeks. Hematological variables were determined twice prior to the administration and at 4 and 8 weeks after the administration. The platelet aggregation in vitro was determined by the turbidimetric method and the level of circulating platelet aggregates was determined according to the method of Wu-Hoak. Erythrocyte deformability was determined according to the method based on the examination of passing erythrocytes through a filter containing pores smaller than the undeformed cells. Collagen-, arachidonic acid- and PAF-induced platelet aggregation was decreased after nicergoline administration. Erythrocyte deformability was increased and plasma viscosity was also decreased after the administration. Thus the improvement of platelet aggregation, plasma viscosity and erythrocyte deformability in cerebral infarction may prevent disturbing blood flow and may contribute to prevention of formation and progression of thrombosis and atherosclerosis in geriatric patients with cerebral infarction.

Aged↗
PubMed1995

Platelet aggregability in vivo is attenuated by verapamil but not by metoprolol in patients with stable angina pectoris.

The effects of 1 month of treatment with either verapamil or metoprolol on several aspects of platelet function were studied at rest and during physical exercise or mental stress in patients with stable angina pectoris participating in the Angina Prognosis Study in Stockholm. Platelet aggregability was measured by filtragometry ex vivo, which reflects platelet aggregability in vivo and by Born aggregometry in vitro. Platelet secretion in vivo was assessed by measurements of beta-thromboglobulin in plasma. Verapamil reduced plasma norepinephrine levels (from 2.6 +/- 1.0 to 2.2 +/- 1.0 nmol/L; p < 0.01) and attenuated platelet aggregability at rest (filtragometry readings were prolonged from 219 to 295 seconds; p < 0.05, n = 46). Aggregability in platelet-rich plasma was not influenced. Metoprolol did not significantly affect filtragometry readings (n = 58) or aggregability in vitro (there was a tendency toward enhanced adenosine diphosphate sensitivity; p = 0.08). beta-thromboglobulin levels were low (approximately 25 ng/ml) and not influenced by either treatment. Physical exercise (bicycle ergometry) increased platelet aggregability in vivo both before and after drug treatment. Verapamil also attenuated platelet aggregability after exercise, whereas metoprolol had no such effect. Platelet function was not seriously altered by mental stress (Stroop's color word test) despite significant effects on hemodynamics and plasma catecholamines either before or after treatment with either drug. Thus, verapamil attenuates platelet aggregability in patients with stable angina pectoris, whereas metoprolol has no such effect.

Adult↗
PubMed1995

ADP-induced platelet aggregation and actin polymerization. Involvement of GpIIb/IIIa and the effect of Mg2+.

We have investigated the effects of Mg2+ (added to platelet rich plasma [PRP] as 10mM MgCl2 or MgSO4) on the platelet aggregation and actin polymerization that occurs in response to adenosine diphosphate (ADP). The PRP was prepared from blood containing hirudin as anticoagulant. Mg2+ added before 1 microM ADP completely inhibited aggregation and markedly inhibited actin polymerization. Mg2+ (10mM) added before 10 microM ADP converted irreversible aggregation into a reversible response; similarly, apparently irreversible actin polymerization was converted to a reversible response in which polymerization was followed by some actin depolymerization. Mg2+ added after inducing platelet aggregation with 10 microM ADP produced parallel disaggregation of platelets and actin depolymerization. Actin polymerization occurs immediately on adding ADP to PRP (in association with shape change) and further polymerization occurs in association with platelet aggregation. When aggregation (and the actin polymerization associated with this) was prevented by adding M148, a monoclonal antibody directed at the GpIIb/IIIa complex, or simply by avoiding stirring the sample, Mg2+ had no effect on actin polymerization/depolymerization. Thus Mg2+ only affected the changes in actin that were associated with the aggregation response. This was in contrast to iloprost (which acts at the PGI2 receptor to stimulate adenylate cyclase) which induced rapid actin depolymerization when added after ADP stimulation of platelets under circumstances where platelet aggregation was avoided. These results show that Mg2+ affects actin polymerization as well as platelet aggregation, and that it affects the actin polymerization associated with aggregation but not that associated with shape change (in contrast to iloprost which inhibits both).(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1986

Analysis of shear-induced platelet aggregation with population balance mathematics.

Suspensions of blood platelets aggregate and degranulate when subjected to a shearing flow of sufficient intensity. This work examines, by means of a population balance technique, the kinetics of platelet aggregation in a shear field. The particle collision efficiency, epsilon, and the particle void volume fraction, phi, are estimated from particle number density data. The collision efficiency represents the fraction of particle collisions that result in the binding together of the involved particles. We term epsilon and phi population balance properties because they refer to physical characteristics of platelets and aggregates that are pertinent to their aggregation behavior. Experiments focused on the dependence of epsilon on platelet concentration, shearing rate, and time in a controlled shear field. The collision efficiency is lower in dilute platelet suspensions. This finding supports an ADP-mediated mechanism for shear aggregation. The collision efficiency passes through a maximum with respect to shearing rate, suggesting a competition between the opposing effects of increasing platelet activation and increasing collision violence. The collision efficiency is highest during the first ten seconds in the shear field and declines significantly thereafter. Even at its maximum, however, epsilon for shear aggregation is small: only about one in every thousand particle collisions results in binding.

Adult↗
PubMed1982

Platelet aggregation and multiple sclerosis.

Measurements of blood platelet aggregation were carried out in 30 patients suffering from multiple sclerosis (MS) and in 15 healthy individuals. Compared with the control group, the MS patients showed an increase in both spontaneous and induced (ADP and serotonin) platelet aggregation. The possible pathogenetic significance of these results is discussed.

Adenosine Diphosphate↗
PubMed1973

Inhibition of primary ADP-induced platelet aggregation in normal subjects after administration of nitrofurantoin (furadantin).

The evidence indicating that platelets may play a role in the occurrence of certain thromboembolic phenomena has stimulated a search for inhibitors of platelet function. This report presents data to indicate that nitrofurantoin is a potent inhibitor of primary ADP-induced platelet aggregation. The addition of 10 muM nitrofurantoin to citrated platelet-rich plasma obtained from 12 normal subjects produced a 29+/-6% (2 SD) inhibition of the velocity of platelet aggregation induced by 2 muM ADP. The inhibitory effect of nitrofurantoin demonstrated competitive kinetics in respect to ADP. The intravenous (180 mg) or oral (200 mg) administration of nitrofurantoin produced a serum nitrofurantoin concentration ranging from 2.7 to 23 muM in 28 normal subjects. Platelet-rich plasma obtained from these subjects demonstrated inhibition of the velocity of ADP-induced platelet aggregation that correlated with the log of the serum nitrofurantoin concentration (P < 0.001). Collagen-induced platelet aggregation was also inhibited in a dose-related manner, and the bleeding time was significantly prolonged in the two subjects with the highest serum nitrofurantoin concentration. These studies indicate that nitrofurantoin in vivo inhibits platelet function to a degree that is proportional to the serum nitrofurantoin concentration.

Adenosine Diphosphate↗
PubMed1999

A polyclonal antibody to protein disulfide isomerase induces platelet aggregation and secretion.

Monoclonal mouse antiplatelet antibodies against a variety of platelet surface components can activate platelets, causing platelet aggregation and secretion. The mechanism involves binding of the Fab domain to a platelet surface antigen, and the activation occurs through an interaction of the Fc domain with the platelet FcgammaRII receptor. There is almost no information on FcgammaRII receptor-dependent activation of platelets by polyclonal rabbit antibodies. We presently report that a polyclonal rabbit antibody to a platelet surface antigen, protein disulfide isomerase, induces platelet aggregation and secretion. These effects are seen with concentrations of the antiprotein disulfide isomerase antibody as low as 25 to 40 microg/mL. Fab and F(ab')2 preparations of the rabbit antiprotein disulfide isomerase antibody do not cause aggregation. Fab made from the rabbit antiprotein disulfide isomerase antibody as well as a monoclonal antibody to the FcgammaRII (IV.3) receptor block the aggregation and secretion responses. Aggregation and secretion are inhibited by an antiglycoprotein IIbIIIa antibody, which blocks fibrinogen binding and wortmannin, an inhibitor of phosphoinositide 3-kinase. Aspirin, prostaglandin E1, and Ethylenediamine-tetraacetic acid (EDTA) also block the platelet responses. These data suggest that activation of platelets by polyclonal antibodies occurs by mechanisms similar to those found with activating monoclonal antibodies.

Animals↗
PubMed1979

Effects of dilazep (AS-05) on human blood platelet aggregation.

The effects of tetrahydro-1H-1,4-diazepine-1,4 (5H)-dipropanol-3,4,5-trimethoxybenzoate diester (dilazep) on platelet aggregation were studied by aggregometer-technique in vitro, using platelet-rich plasma obtained from healthy subjects. As agents for platelet aggregation, norepinephrine, at a concentration of 10 micrograms/ml, and ADP, at a concentration of 1 microgram/ml, were added. There was some inhibition when compared to controls with 200 micrograms/ml of dilazep, and complete inhibition on both norepinephrine and ADP-induced platelet aggregation with 500 micrograms/ml. The effects of dilazep on platelet aggregation before and after administration (75 mg) in vivo, using platelet-rich plasma obtained from healthy subjects, were studied in accordance with the screen filtration pressure method. In all cases the inhibitory tendency was first seen 30 min after administration. It reached a peak after 60--120 min and tended to return to the initial value after 180 min. The effects of dilazep (150 mg/day for 4 weeks) and verapamil hydrochloride (240 mg/day for 4 weeks) on platelet aggregation in vivo, using plasma obtained from sixteen patients with coronary insufficiency, were determined in each group before and after drug administration. A significant difference in the group receiving dilazep was found at tO = 3.2643 and less than 0.01 in the Student's t-test (two dependent sample cases). In the experiments with verapamil hydrochloride there were no significant differences in the results before and after administration. However, there was a slight tendency towards a decrease of effects two weeks after administration.

Adenosine Diphosphate↗
PubMed2006

Cyclooxygenase-2 inhibitors enhance shear stress-induced platelet aggregation.

OBJECTIVES: We aimed to investigate the effect of parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on in vivo shear stress-induced platelet aggregation in a rat model of arterial bypass with focal narrowing. BACKGROUND: Long-term use of COX-2 inhibitors is associated with increased incidence of adverse cardiovascular events, especially in patients with a history of cardiovascular disease. These patients are at risk for thrombotic occlusion of arterial stenoses initiated by shear stress-induced platelet aggregation. METHODS: To mimic the combination of a tight arterial stenosis and high shear stress in rats, an extracorporeal shunt from carotid to femoral artery was compressed by the rollers of a pump. Platelet aggregation was continuously measured by a photometric detector in the shunt. RESULTS: Pretreatment with parecoxib (20 mg/kg) almost doubled shear stress-induced platelet aggregation (188% vs. 100% in control subjects, p = 0.0003). This was accompanied by a fall in plasma 6-keto-prostaglandin F(1alpha) from 100 +/- 25 pg/ml to 36 +/- 11 pg/ml (p < 0.0001). Enhanced platelet aggregation was also observed with high-dose aspirin (150 mg/kg) (146%; p = 0.02) but not with low-dose aspirin (25 mg/kg), which reduced aggregation (68%; p = 0.01). The effect of parecoxib was neutralized by low-dose (1 mg/kg) clopidogrel (from 188% to 92%; p = 0.0001), but not by low-dose aspirin (from 188% to 177%; p = NS). CONCLUSIONS: In the presence of an arterial stenosis, COX-2 inhibitors enhance shear stress-induced platelet aggregation. This enhancement was prevented by low-dose clopidogrel but not by low-dose aspirin. Clopidogrel might therefore allow COX-2 inhibitors to be used without raising risk of thrombotic occlusion.

Animals↗
PubMed1990

Octimibate inhibition of platelet aggregation: stimulation of adenylate cyclase through prostacyclin receptor activation.

Octimibate inhibited ADP- and collagen-induced platelet aggregation in human, rabbit and rat platelet-rich plasma. Washed human platelets treated with octimibate had elevated cyclic AMP (cAMP) levels and cAMP-dependent protein kinase activity. When whole platelets were incubated with radiolabeled phosphate, octimibate produced an increase in the phosphorylation of platelet proteins with relative molecular weights of 22, 26, 50 and 80 kilodaltons. This pattern of protein phosphorylation is identical to that observed when the platelets were treated with forskolin, phosphodiesterase inhibitors or other compounds that elevate platelet cAMP levels. Octimibate also inhibited the rise in intracellular Ca++ caused by thrombin, as measured using Fura-2-loaded platelets, which is consistent with octimibate's ability to elevate platelet cAMP levels. When isolated platelet plasma membranes were treated with octimibate, adenylate cyclase activity was stimulated, reaching maximal activation at 1 microM octimibate. (The maximal activation of adenylate cyclase observed with octimibate is 70-75% of that observed with 10 microM PGE1.) This stimulation of platelet adenylate cyclase activity was enhanced by GTP. Octimibate competed for radiolabeled prostaglandin E1 and lloprost binding to isolated platelet membranes at submicromolar concentrations, but did not compete with radiolabeled prostaglandin D2 binding. These studies suggest that octimibate inhibits platelet aggregation by activating platelet adenylate cyclase through stimulation of platelet prostacyclin receptors.

Adenylyl Cyclases↗
PubMed1983

Antiaggregant effect of indobufen (K3920) measured by the platelet aggregate filtration pressure test (PAFP).

The platelet aggregate filtration pressure test (PAFP) was used to study the aggregant activity of single doses of 200 mg indobufen, administered either orally or by i.v. injection. This double-blind study using placebo in a crossover design was conducted in twelve patients whose baseline aggregation values were high. The compound showed markedly different antiaggregant activity from placebo at the various observation times after administration. The two administration routes did not produce any significant differences. The PAFP test can be useful in identifying atherosclerotic patients with platelet hyperaggregation, and for clinical pharmacology studies with platelet antiaggregant drugs.

Administration, Oral↗
PubMed1995

Tumor cell-induced platelet aggregation in vitro by human pancreatic cancer cell lines.

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is considered to be a critical step in hematogenous metastasis. METHODS: TCIPA was studied in vitro in six human pancreatic carcinoma cell lines (PC 3, PC 44, AsPC1, BxPC3, Capan2, Panc1). RESULTS: Whereas all cell lines induced aggregation of washed platelets in the presence of minimal amounts of platelet-poor plasma, five cell lines also induced aggregation of platelets in platelet-rich plasma. The thrombin-antagonist hirudin inhibited TCIPA in all cell lines indicating that TCIPA is thrombin-dependent. Since pretreatment of tumor cells with phospholipase A2 or C inhibited TCIPA, the thrombin-generating activity might be confined to the tumor cell surface. Further support for a prothrombinase activity was provided by the observation that all cell lines were able to induce the aggregation of washed platelets after addition of purified coagulation factors II and V. CONCLUSIONS: Pancreatic carcinoma cells are able to induce platelet aggregation via activation of thrombin. This might support metastasis in pancreatic cancer and possibly explain the incidence of thrombosis in this tumor.

Antithrombins↗