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 1,531 records · Page 85Linked to original sources
PubMed1991

Platelet aggregation is inhibited by a nitric oxide-like factor released from human neutrophils in vitro.

Thrombin-induced platelet aggregation was inhibited in vitro by washed human neutrophils. Aggregation was inhibited in a neutrophil concentration dependent manner but glutaraldehyde fixed neutrophils had no significant effect on platelet aggregation. The neutrophil-derived inhibitory factor had the pharmacological profile of nitric oxide. Its action was potentiated by both superoxide dismutase and M&B22, 948, a selective cyclic guanosine monophosphate (cyclic GMP) phosphodiesterase inhibitor. Haemoglobin lessened this inhibitory action of neutrophils. L-Arginine, the substrate for nitric oxide formation, enhanced inhibition, whereas, L-canavanine, a structural analogue of L-arginine, prevented it. Nitric oxide release by neutrophils antagonized platelet ATP secretion and thromboxane B2 release. Inhibition was mediated by nitric oxide activation of guanylate cyclase with a subsequent rise in cyclic GMP. When neutrophils were stimulated with formyl-met-leu-phe, there was a further increase in platelet cyclic GMP. This was enhanced by superoxide dismutase, but lessened by haemoglobin. Leukotriene B4 stimulation of neutrophils promoted inhibition of platelet aggregation. Leukotriene B4 alone had no direct effect on thrombin-induced aggregation of platelets. Platelets, when incubated with neutrophils and stimulated with calcium ionophore A23187, increased leukotriene B4 production by neutrophils in a platelet concentration dependent manner. Platelets alone were unable to release leukotriene B4. The action of platelets in haemostasis is modified as they come into contact with neutrophils. This may be an important physiological mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Inhibition of prostaglandin E1-responsive platelet adenylate cyclase by heparin: a study of the mechanism of inhibition and its relevance to platelet aggregation.

1 Heparin can produce platelet aggregation in vitro and in vivo; it has been proposed that this may be due to the reported inhibition of the prostaglandin E(1) (PGE(1))-stimulated adenylate cyclase of the platelet by heparin.2 The effect of heparin on the cyclic adenosine 3',5'-monophosphate (cyclic AMP) response to PGE(1) was measured in intact and broken platelets both in vitro and in platelets obtained from normal subjects during intravenous infusion with herapin.3 In platelet lysates, heparin produced a dose-related inhibition of PGE(1)-stimulated adenylate cyclase. The maximum response to PGE(1) was reduced, with half-maximal inhibition occurring at 3 mug/ml heparin. This inhibition could be prevented by protamine sulphate.4 Heparin did not affect PGE(1)-stimulated cyclic AMP production in intact platelets either in vitro or in platelets taken during the infusion of 5,000iu heparin over 2h to 2 normal volunteers. Similarly, preincubation of platelets with heparin for up to 3h at 37 degrees C did not affect platelet adenylate cyclase.5 The effects of heparin were very similar to those of fluoride on the platelet adenylate cyclase: heparin and fluoride increased basal enzyme activity slightly (3-4 fold) but their effects were not additive; both inhibited the response to PGE(1) by approximately 50% when added directly to the assay and the inhibitory effects of the two were not additive; preincubation of membranes with either heparin or fluoride produced an irreversible state of inhibition.6 As heparin inhibits PGE(1)-stimulated adenylate cyclase activity only in broken platelets, we suggest that the aggregatory effects of heparin are probably independent of any action on cyclic AMP production.

Adenylyl Cyclase Inhibitors↗
PubMed2004

A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation.

Flow cytometry, singlet platelet counting, and optical aggregation have been used to monitor clopidogrel and glycoprotein IIb/IIIa (GPIIb/IIIa) platelet antagonists. Optical aggregation is considered the gold standard, but neither it nor flow cytometry is convenient in larger-scale clinical studies or point-of-care systems. Singlet platelet counting, a point-of-care assay correlated with optical platelet aggregation, only provides a measurement of platelet function at a single point in time. The Thrombelastograph is used to assay whole blood for thrombin-generated maximal clot-shear elasticity, referred to as the maximal amplitude (MA). Although platelet dysfunction, thrombocytopenia, and the in vitro effect of strong inhibitors such as IIb/IIIa antagonists can be observed, with thrombin generation milder platelet inhibitors cannot be assessed. We modified the Thromboelastograph assay, using reptilase and factor XIIIa, to form a clot, without thrombin generation, in heparinized whole blood. The resulting clot MA is dependent on added platelet agonists such as ADP or arachidonic acid, is sensitive to platelet antagonists, and provides a continuous measure of platelet function more analogous and better correlated with optical aggregation. This novel modification of the Thromboelastograph assay should prove to be a useful point-of-care whole-blood assay with which to monitor the effects of GPIIb/IIIa, ADP, and thromboxane A(2)-receptor-inhibiting drugs in patients.

Adenosine Diphosphate↗
PubMed1984

Platelet aggregation in variant angina: its relation to plasma catecholamines.

We concurrently measured plasma catecholamine levels and platelet aggregation in patients with variant angina, effort angina and old myocardial infarction. Platelet aggregability was lower in variant angina than in effort angina and old myocardial infarction. Plasma concentrations of epinephrine and norepinephrine in the variant angina group showed higher values than those in the effort angina group and the old myocardial infarction group. Moreover, there was a statistically significant negative correlation between plasma catecholamine concentration and ADP-induced platelet aggregation. These findings suggest that the lower platelet aggregation is related to the higher concentration of plasma catecholamine in variant angina.

Adenosine Diphosphate↗
PubMed2001

Anti-vWf antibodies induce GPIbalpha and FcgammaRII mediated platelet aggregation only at low shear forces.

BACKGROUND/METHODS: Anti-von Willebrand factor (vWf) antibody mediated platelet activation was studied using 2 monoclonal anti-vWf antibodies promoting the binding of vWf to GPIbalpha: 1C1E7 (IgG2a) reacting with the vWf N-terminus and 75H4B12 (IgM), characterized in this paper and studied in association with 1C1E7. RESULTS: 75H4B12 binds to an N-terminal epitope in vWf, different from that reacting with 1C1E7. When com-bined, 1C1E7 and 75H4B12 promoted vWf binding to isolated GPIb under static conditions, even in the absence of ristocetin or botrocetin, and induced platelet aggregation synergistically in the presence of zero to subthreshold ristocetin concentrations. Specific inhibitors of GPIbalpha-vWf interactions prevented vWf binding to GPIbalpha in ELISA and during platelet aggregation. In addition, the 1C1E7 dependent platelet aggregation involved Fc receptor mediated platelet activation, a phenomenon even more pronounced when 1C1E7 and 75H4B12 were combined. A 75H4B12 binding phage expressing a peptide homologous with vWf sequence 88-95 neutralized the antibody induced platelet activation. However, at arterial shear rates, both 1C1E7 and 75H4B12 potently prolonged cartridge closure times in the PFA-100, compatible with inhibition of platelets by vWf, unfolded by the combined action of shear stress and antibodies. CONCLUSIONS: We conclude that antibodies directed against different epitopes in the N-terminus of vWf modify the folded vWf structure synergistically and enhance A1 domain mediated vWf binding to platelet GPIb at low shear forces. In addition, once platelet-bound, IgG antibodies potently activate platelets via the FcgammaII receptor. Thus, such antibodies may promote immune mediated thrombosis at low shear rates, typical of the venous circulation. In contrast, at arterial shear rates, anti-vWf antibodies may rather compromise platelet function following enhanced binding of the unfolded vWf multimers to platelets, shielding platelets from interacting with subendothelial and soluble ligands.

Antibodies, Monoclonal↗
PubMed1980

[Limits of platelet aggregation tests for investigating thromboses (author's transl)].

Three methods--spontaneous aggregation, ADP-induced aggregation and levels of circulating platelet aggregates--were used to test for platelet hyperaggregation in 87 adult patients divided into three groups. Group A comprised 26 patients with severe arterial diseases, including cerebral vascular accidents (16) and peripheral thrombosis (10) ; group B consisted of 31 patients with venous conditions, including deep phlebitis (22) and recurrent thrombo-embolic disease (9) ; group C, which served as control, comprised 30 patients with various non-vascular disorders. Spontaneous aggregation and enhanced reactivity to ADP correlated well with each other and were more frequent in patients with vascular diseases. However, one-third of patients in group C had pathological results, while one-third of patients in groups A and B had normal results, independently of any clinical particularity or therapeutic regimen. There were no significant differences between the three groups with regard to circulating platelet aggregates. These tests, therefore, appear to be of statistical and epidemiological interest, but of questionable practical value.

Adenosine Diphosphate↗
PubMed1991

The effect of doxazosin on platelet aggregation in normotensive subjects and patients with hypertension: an in vitro study.

An in vitro assay was used to investigate the effects of doxazosin on the platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate. Platelet-rich plasma from normotensive subjects and patients with hypertension was compared. Doxazosin produced a concentration-dependent inhibition of platelet aggregation in both groups, but significantly lower concentrations were required to inhibit platelet aggregation in plasma taken from patients with hypertension. The concentrations of doxazosin that inhibited platelet aggregation in vitro were similar to those that are used clinically to control blood pressure in patients with hypertension.

Adult↗
PubMed1989

[New methodical approach to the study of platelet aggregation in vitro].

A new approach to the investigation of the kinetics of platelet aggregation is described. The method is based on the analysis of light transmission fluctuations produced on the changes in the number of platelets in optical channel. The relative dispersion of the fluctuations of transmitted light intensity was used as a parameter to estimate the degree of platelet aggregation. Application of this method for the analysis of platelet aggregation permits to get new information about this process.

Adenosine Diphosphate↗
PubMed1993

Salivary gland extracts from the deerfly contain a potent inhibitor of platelet aggregation.

Salivary gland extracts of the deerfly contain a potent inhibitor of platelet aggregation, which assists the insect in obtaining a blood meal. The extract prevents platelet aggregation induced by ADP, thrombin, and collagen and inhibits fibrinogen binding to the glycoprotein IIb/IIIa receptor on platelets. The active component in deerfly salivary gland extract appears to be a protein that is comparatively more potent than the disintegrins present in viper venoms. Isolation and characterization of this protein may provide different directions in therapeutics and studies of normal platelet physiology.

Adenosine Diphosphate↗
PubMed2001

The effect of a novel glycoprotein IIb/IIIa antagonist, SR 121566A, on platelet aggregation and activation in rhesus monkeys.

SR 121566A represents a peptidomimetic glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor 3-[N- 4-[4-(aminoiminomethyl)phenyl]-1,3-thiazol-2-yl ) -N-(1-carboxymethylpiperid-4-yl) amino] propionic acid, trihydrochloride. To investigate the intravenous and subcutaneous pharmacodynamics of this agent, a primate model ( Macaca mulatta) was used. The IC50 for adenosine diphosphate (ADP) (10 micromol/L)-induced platelet aggregation in this primate platelet system was found to be 45 +/- 6 nmol/L. Comparatively in the human platelet rich plasma system, SR 121566A demonstrated an IC50 of 39 +/- 4 nmol/L. Graded doses of SR 121566A in the range of 25-400 microg/kg were administered intravenously. Blood samples were drawn from individual groups of primates (n = 4-6) at varying periods of time up to 24 hours after administration of SR 121566A. The pharmacodynamic effects were measured by platelet aggregation using ADP (10 micromol/L) as an agonist. In addition, flow cytometric methods were used to measure thrombin receptor-activating peptide (TRAP) (6.25 micromol/L)-induced platelet activation. In the subcutaneous studies, 50, 100, 250, and 400 microg/kg of SR 121566A was administered with an identical blood-drawing schedule and analysis as with the intravenous studies. In the intravenous studies, all doses of SR 121566A produced > 80% inhibition of platelet aggregation 5 minutes after the administration of the drug. The duration of the inhibitory effect is proportional to the dose administered and the 50% recovery time ranged from 2 to 15 hours. By flow cytometry, TRAP-induced P-selectin expression was also blocked for a varying duration of time in a dose-dependent fashion. The subcutaneous studies showed > 90% inhibition of platelet aggregation, which was observed at 15 minutes after administration of both 50 and 100 microg/kg of the drug. The recovery time after the subcutaneously administered doses was found to be shorter than the intravenously administered doses. These studies demonstrate that SR 121566A is an effective platelet inhibitor with predictable pharmacokinetic and pharmacodynamic characteristics.

Adenosine Diphosphate↗
PubMed1994

Effect of nisoldipine on red cell deformability and platelet aggregation in stroke patients.

Reduced red cell deformability and increased platelet aggregability are assumed to contribute to various ischemic diseases, and it has been postulated that these abnormalities may be improved by drug treatment. In this study, the effect of nisoldipine (Bay K 5552, CAS 63675-72-9) on red cell deformability and platelet aggregation in patients with chronic ischemic cerebrovascular disease and hypertension was examined. Administration of nisoldipine for 4 weeks caused a significant improvement of red cell deformability and platelet aggregability without causing any adverse effects.

Adenosine Diphosphate↗
PubMedDate not supplied

The 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride inhibits acute platelet aggregation in injured endothelium.

In this study, the effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2A receptor antagonist, on platelet aggregation at the site of injured carotid artery endothelium was examined. The rat common carotid artery was clamped for 30 min to induce endothelial injury. Sarpogrelate hydrochloride was administered before and after the injury, and the effects were compared with those in rats receiving sham operation only and those receiving clipping injury but no sarpogrelate hydrochloride. The animals were killed 24 h after the procedure. The common carotid artery was examined by scanning electron microscopy and stained immunochemically for factor VIII. Sarpogrelate hydrochloride treatment was associated with reduced aggregation of platelets on electron microscopy and lower expression of factor VIII at the injured intima. Sarpogrelate hydrochloride has an inhibitory effect on platelet aggregation at the intima in the acute stage after injury, suggesting that this drug may be used to prevent early ischaemic complications after surgical or endovascular arterial intervention.

Animals↗
PubMed1997

Cerastatin, a new potent inhibitor of platelet aggregation from the venom of the Tunisian viper, Cerastes cerastes.

Cerastatin, a potent platelet aggregation inhibitor, was purified by gel filtration on Sephadex G-75, followed by two ion exchange chromatographies on Mono-S columns. Cerastatin is a neutral glycoprotein (pI = 6.2) of 32 kDa, made up of at least three subunits. It is devoid of phospholipase A2, esterase, fibrinogenolytic and amidolytic activities. It inhibits aggregation of washed platelets, induced by either collagen, PAF acether or thrombin, with similar IC50 of 2.3 nM. Cerastatin also inhibits the thrombin-induced clot retraction of platelet-rich plasma. It does not inhibit the amidolytic or the procoagulant activities of thrombin Cerastatin caused no lytic effect on platelet membranes since it did not cause release of lactate dehydrogenase. Pretreatment of platelets with cerastatin irreversibly inhibits the aggregation induced by thrombin. Also cerastatin completely inhibits the fibrinogen-induced aggregation of alpha chymotrypsin-treated platelets. Cerastatin therefore inhibits platelet aggregation by interfering with the interaction of fibrinogen with fibrinogen receptors.

Animals↗
PubMed1980

A potent platelet aggregation inducer purified from Trimeresurus mucrosquamatus snake venom.

A non-coagulant platelet aggregation inducer (called platelet 'aggregoserpentin') was isolated from Trimeresurus mucrosquamatus snake venom by CM-Sephadex chromatography and purified by gel filtration. It was homogeneous as judged by the ultracentrifugal analysis and electrophoresis on polyacrylamide gel and cellulose acetate membrane. The molecular weight was estimated to be 68 000 as judged by the SDS-polyacrylamide gel electrophoresis and gel filtration on Sephadex G-75. The ultracentrifugal analysis gave 3.19 Svedberg units. It was a protein-polysaccharide complex containing 340 amino acid residues and 50% carbohydrate per molecule. The isoelectric point was pH 5.4. It did not possess any of the hydrolase enzymatic properties which were found in the crude venom. The minimal concentration of 'aggregoserpentin' necessary to induce platelet aggregation was 10 ng/ml, about one four-hundredth of that of the crude venom. It did not cause lysis of platelets because lactate dehydrogenase was not found in supernatant after complete aggregation. An intravenous injection of 'aggregoserpentin' (35 microgram/kg) into rabbit ear marginal vein caused marked decrease of platelet number to approx. 10-20% of that of the control.

Animals↗
PubMedDate not supplied

Effect of oral and intravenous diltiazem on whole blood platelet aggregability.

Diltiazem, a calcium channel blocker, is known to suppress platelet function in vitro. However, its in vivo effects on platelets have been controversial. The effect of diltiazem on both human and calf platelets was studied using impedance whole-blood aggregometry. In vitro, platelet aggregation induced by ADP (5 microM) or collagen (1 micrograms/ml) was significantly suppressed by 0.1 to 1.0 mM (45 to 450 micrograms/ml) of diltiazem in both species. In calves weighting 70 to 90 kg, platelet aggregability did not change after the oral administration of 180 mg diltiazem. In this condition, diltiazem was not detected in plasma samples. Intravenous injection of 0.5 mg/kg diltiazem also did not significantly alter the aggregability, although the PR interval on the ECG elongated (40 msec, p < .05), mean arterial pressure dropped (14 mmHg, p < .05), and diltiazem was readily detected in plasma (199 ng/ml, 0.4 microM). In conclusion, platelet aggregability is not altered by a clinical dosage of diltiazem that is sufficient to induce hemodynamic changes with therapeutic plasma concentrations.

Administration, Oral↗
PubMed1996

Sensitivity to platelet aggregation appears related to the lipoprotein profile and atherosclerosis risk in humans and across species.

Platelet aggregation sensitivity was assessed in nine species of animals, including humans, with disparate susceptibility to atherosclerosis and a wide range in their LDL/HDL profiles. Platelet aggregation sensitivity between species varied almost 20-fold. The most sensitive platelets were found in humans and rabbits, followed by squirrel and rhesus monkeys with the most resistant platelets in cats, hamsters, rats, cebus monkeys, and gerbils. Species platelet aggregation sensitivity correlated well with relative susceptibility to atherosclerosis. The relationship between LDL/HDL ratio and platelet aggregation was significant, both across species (r = 0.76, without cebus) and within species (r = 0.50 for humans).

Adenosine Diphosphate↗
PubMed2000

[The effect of triflusal on human platelet aggregation and secretion: the role of nitric oxide].

INTRODUCTION AND AIMS: The thrombotic process is a multicellular phenomenon in which not only platelets are involved but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal reduced platelet aggregation by stimulating nitric oxide (NO) production by neutrophils. The aim of the present study was to evaluate whether the in vivo treatment with triflusal could also modify the ability of neutrophils to produce NO. Furthermore, the role of NO released by neutrophils on platelet aggregation and secretion was also tested. METHODS: The study was performed in 12 healthy volunteers of 32 +/- 6 years of age. The volunteers were treated with triflusal (600 mg/day) for 5 days and platelets and neutrophils were isolated before and after treatment. The ability of neutrophils to produce NO and the capacity of inhibiting platelet aggregation and secretion of transforming growth factor-beta (TGF-beta) were assessed. RESULTS: After the treatment with triflusal we obtained the following results: a) an increase in NO production by neutrophils; b) potentiation of the inhibition of platelet aggregation by neutrophils, an effect that was reverted by incubating neutrophils with an L-arginine antagonist, L-NAME, and c) the presence of neutrophils reduced the release of TGF-beta by platelets measured as index of platelet secretion by a NO-independent mechanism. CONCLUSIONS: Triflusal (600 mg/day/5 days) stimulated NO production by neutrophils. After the treatment with triflusal, neutrophils inhibited both platelet aggregation and secretion. The antiaggregating effect of neutrophils was an NO-dependent mechanism while the inhibition of platelet secretion mediated by neutrophils after the treatment with triflusal was an NO-independent mechanism.

Adult↗
PubMed1998

Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort.

BACKGROUND: Platelets are involved in myocardial infarction but evidence of prediction of infarction by measures of platelet function are sparce. METHODS: Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results from 364 men were excluded, 80 of whom had not fasted before venepuncture; most of the others were excluded because antiplatelet medication had been taken shortly before the platelet tests. During the five years following the platelet tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of platelet aggregation was found to be significantly predictive of incident IHD. The possibility that platelet function is predictive for only a limited time after it is characterised, and that prediction falls off with time, was tested. When IHD events are grouped by their time of occurrence after aggregation had been measured, the test results show a gradient suggestive of prediction of early IHD events. Thus, 24% of the men who had an event within 500 days of the test had had a high secondary response to ADP while only 12% of those whose IHD event had been 1000 or more days after the test had shown a high platelet response at baseline. The trend in these proportions is not significant. CONCLUSIONS: Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in the Caerphilly cohort study. No measure of aggregation was found to be predictive of IHD.

Adenosine Diphosphate↗